Primary Outcomes

Description: Weight change during counseling and/or % of weight change during program and maintained over remaining time period will be assessed in both the diabetes and pre-diabetes cohorts.

Measure: Weight change

Time: 10 years

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Secondary Outcomes

Description: In the pre-diabetes cohort, diabetes incidence will be determined as the % of patients who develop diabetes following weight counseling. In the diabetes cohort, uncontrolled diabetes will be measured.

Measure: Diabetes Incidence

Time: 10 years

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Description: Incidence of hospitalization will be assessed for COVID-19 positive patients

Measure: Hospitalization

Time: 1 year

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Description: Incidence of intubation will be assessed for COVID-19 positive patients

Measure: Intubation

Time: 1 year

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Description: Incidence of death will be assessed for COVID-19 positive patients

Measure: Death

Time: 1 year

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Primary Outcomes

Description: The investigators will examine the changes in use of MHV from baseline to 6 month follow-up, including use of secure messaging, Blue Button, and prescription refills.

Measure: Changes in My HealtheVet patient portal use

Time: Baseline & 6 month follow up

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Primary Outcomes

Description: To determine if there will be a greater mean reduction from baseline in HbA1c achieved after 26 weeks of oral double-blind add-on therapy of dapagliflozin 5 mg or saxagliptin 2.5 mg (with titration to the high-dose for those who do not achieve the glycemic target of HbA1c < 7% at 12 weeks) compared to placebo in pediatric T2DM subjects with HbA1c levels of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin.

Measure: Change from baseline in HbA1c at Week 26

Time: 26 weeks

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Secondary Outcomes

Description: To determine if there will be a greater mean reduction from baseline in Fasting Plasma Glucose (FPG) achieved after 26 weeks of oral double-blind add-on therapy of dapagliflozin 5 mg or saxagliptin 2.5 mg (with titration to the high-dose for those who do not achieve the glycemic target of HbA1c <7% at 12 weeks) compared to placebo in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin

Measure: Change from baseline in Fasting Plasma Glucose at Week 26

Time: 26 weeks

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Description: To compare the percentage of subjects with baseline HbA1c ≥ 7% who achieve an HbA1c level < 7.0% after 26 weeks of oral double-blind add-on therapy of dapagliflozin 5 mg or saxagliptin 2.5 mg (with titration to the high-dose for those who do not achieve the glycemic target of HbA1c <7% at 12 weeks) versus placebo in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin

Measure: Percentage of subjects with baseline HbA1c ≥ 7%, who achieve an HbA1c level < 7.0% at Week 26

Time: 26 weeks

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Other Outcomes

Description: To compare the percentage of subjects requiring glycemic rescue medication or discontinuing study medication due to lack of efficacy with dapagliflozin or saxagliptin against the percentage with placebo during 26 weeks of oral double-blind add-on treatment in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin.

Measure: Percentage of subjects who require glycemic rescue medication or discontinue the study medication due to lack of efficacy during the 26-week treatment period

Time: 26 weeks

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Description: To assess the mean change from baseline in HbA1c achieved with dapagliflozin therapy versus placebo, and separately, achieved with saxagliptin therapy versus placebo after 52 weeks of oral blinded add-on treatment in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin.

Measure: Change from baseline in HbA1c at Week 52

Time: 52 weeks

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Description: To assess the mean change from baseline in FPG achieved with dapagliflozin therapy versus placebo, and separately, achieved with saxagliptin therapy versus placebo after 52 weeks of oral blinded add-on treatment in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin

Measure: Change from baseline in FPG at Week 52

Time: 52 weeks

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Description: To assess the percentage of subjects with baseline HbA1c ≥ 7% who achieve an HbA1c level < 7.0% after 52 weeks of oral blinded add-on therapy with dapagliflozin versus placebo, or saxagliptin versus placebo in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin.

Measure: Percentage of subjects with baseline HbA1c ≥ 7% who achieve an HbA1c level < 7.0% at Week 52

Time: 52 weeks

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Primary Outcomes

Description: Aortic (carotid to femoral) PWV will be determined by means of applanation tonometry. It will be calculated as the median of three consecutive PWV recordings.

Measure: The effect of a LiPA intervention program on reducing aortic carotid-to-femoral pulse-wave velocity (PWV) in patients with type 2 diabetes.

Time: Change from baseline PWV at 6 months.

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Description: Carotid distensibility will be determined at the left common carotid by means of arterial ultrasound.

Measure: The effect of a LiPA intervention program on increasing carotid distensibility in patients with type 2 diabetes.

Time: Change from baseline carotid distensibility at 6 months.

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Secondary Outcomes

Description: Daily activity levels will be measured by activPAL3™ physical activity monitor. The participants will wear the device fixated on their upper leg for 8 consecutive days at each measurement moment. ActivPAL measures total standing time, sedentary time (sitting or lying down), and stepping time (physical activity).

Measure: Feasibility of a LiPA intervention program on reducing sedentary time as measured by activPAL

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: Measurement of any changes in blood pressure

Measure: The effect of a LiPA intervention on changes in blood pressure.

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: Measurement of any changes in waist -circumference

Measure: The effect of a LiPA intervention on waist -circumference in cm.

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: The EQ-5D is a short questionnaire that covers five dimensions of health: Mobility, Self-Care, Usual Activities, Pain/Discomfort and Anxiety/Depression. The EQ-5D includes 5 questions with 5 answer options each, ranging from 1 ('no problems') to 5 ('severe limitation'). A summary index with a maximum score of 1 can be computed from these five dimensions by means of a converion table. A score of 1 indicates the best health status. Additionally, there is a visual analogue scale (VAS) to indicate the general health status with scores ranging from 0 ('the worst health you can imagine') to 100 ('the best health you can imagine').

Measure: The effect of a LiPA intervention on quality of life as measured through the Dutch versions of the EQ-5D questionnaire.

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: The PHQ-9 is a self-administered questionnaire based on the DMS-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for a major depressive disorder. It comprises nine items rated on a 4-point scale, ranging from 0 = "not at all" to 3 = "nearly every day". The PHQ-9 scale will also be used as a dichotomous variable with a pre-defined cut-off level of 10, which represents the presence of clinically relevant depressive symptoms.

Measure: The effect of a LiPA intervention on depressive symptoms with the use a validated Dutch version of the 9-item Patient Health Questionnaire (PHQ-9).

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: Daily activity levels will be measured by activPAL3™ physical activity monitor. The participants will wear the device fixated on their upper leg for 8 consecutive days at each measurement moment. ActivPAL measures total standing time, sedentary time (sitting or lying down), and stepping time (physical activity). Stepping time (physical activity) is further classified into higher intensity physical activity (minutes with a step frequency >110 steps/min during waking time) and lower intensity physical activity (minutes with a step frequency ≤110 steps/min during waking time).

Measure: Feasibility of a LiPA intervention program on increasing standing and stepping time as measured by activPAL.

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: Measurement of any changes in fasting blood glucose.

Measure: The effect of a LiPA intervention on fasting blood glucose

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: Measurement of any changes in HbA1c.

Measure: The effect of a LiPA intervention on HbA1c.

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: Measurement of any changes in total cholesterol.

Measure: The effect of a LiPA intervention on total cholesterol.

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: Measurement of any changes in HDL- and LDL-cholesterol.

Measure: The effect of a LiPA intervention on HDL- and LDL-cholesterol.

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: Measurement of any changes in triglycerides

Measure: The effect of a LiPA intervention on triglycerides.

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: Measurement of any changes in glucose lowering medication.

Measure: The effect of a LiPA intervention on glucose lowering medication.

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: Measurement of any changes in hip -circumference

Measure: The effect of a LiPA intervention on hip -circumference in cm.

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: Measurement of any changes in body composition as measured by bio electrical impedance.

Measure: The effect of a LiPA intervention on body composition

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: The SF-36 is a generic and easily self-administered quality of life instrument. The SF-36 questionnaire measures health on eight multi-item dimensions, covering functional status, well-being, and overall evaluation of health. In six of these eight dimensions, participants rate their responses on a three or six point scale. For each dimension, item scores are coded, summed, and transformed on to a scale from 0 (worst health) to 100 (best health).

Measure: The effect of a LiPA intervention on quality of life as measured through the Dutch version of the SF-36 questionnaire.

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: Measurement of circulating immune cells using flow cytometry from fresh whole blood. In addition, measurement of circulating cytokines to assess the activation state of immune cells, and store immune cells for functional tests.

Measure: The effect of a LiPA intervention program on immune cells.

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Description: Microvascular function will be evaluated in both the retina and the skin. Which will be determined with the use of fundoscopy and Skin laser Doppler flowmetry.

Measure: The effect of a LiPA intervention program on microvascular function

Time: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).

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Primary Outcomes

Description: Weight in kilograms will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period.

Measure: Change in weight - Randomization 1

Time: Baseline (-14 Days prior to Randomization 1 Visit), 3 Month (Measurement 2) Visit

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Description: Weight in kilograms will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period.

Measure: Change in weight - Randomization 2

Time: 3 Month (Measurement 2) Visit, 6.5 Month (Measurement 3) Visit

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Description: Weight in kilograms will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period.

Measure: Change in weight - Randomization 3

Time: 6.5 Month (Measurement 3) Visit, 10 Month (Measurement 4) Visit

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Description: HbA1c will be measured from a blood sample collected from participants. Blood will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period.

Measure: Change in HbA1C - Randomization 1

Time: Baseline (-14 Days prior to Randomization 1 Visit), 3 Month (Measurement 2) Visit

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Description: HbA1c will be measured from a blood sample collected from participants. Blood will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period.

Measure: Change in HbA1C - Randomization 2

Time: 3 Month (Measurement 2) Visit, 6.5 Month (Measurement 3) Visit

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Description: HbA1c will be measured from a blood sample collected from participants. Blood will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period.

Measure: Change in HbA1C - Randomization 3

Time: 6.5 Month (Measurement 3) Visit, 10 Month (Measurement 4) Visit

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Description: Change in the percent of time spent in hypoglycemia during Continuous Glucose Monitor (CGM) wear time will be assessed between the two weeks of wear from CGM insertion at Baseline Visit (-14 days) and the two weeks of wear from the insertion of the CGM at Measurement Visit 2.

Measure: Difference in Percent Time Spent in Hypoglycemia - Randomization 1

Time: 2 weeks of wear from Baseline Visit (-14 Days), 2 weeks of wear from 3 Month (Measurement 2) Visit

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Description: Change in the percent of time spent in hypoglycemia during CGM wear time will be assessed between the two weeks of wear from CGM insertion at Measurement 2 Visit and from CGM insertion at Measurement 3 Visit.

Measure: Difference in Percent Time Spent in Hypoglycemia - Randomization 2

Time: 2 weeks of wear from 3 Month (Measurement 2) Visit, 2 weeks of wear from 6.5 Month (Measurement 3) Visit

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Description: Change in the percent of time spent in hypoglycemia during CGM wear time will be assessed between the two weeks of wear from CGM insertion at Measurement 3 Visit and from CGM insertion at Measurement 4 Visit.

Measure: Difference in Percent Time Spent in Hypoglycemia - Randomization 3

Time: 2 weeks of wear from 6.5 Month (Measurement 3) Visit, 2 weeks of wear from 10 Month (Measurement 4) Visit

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Secondary Outcomes

Description: Percent fat mass and percent fat free mass will be measured via a dual-energy x-ray absorptiometry (DXA) scan at the beginning and end of this time three-and-a-half-month time period. COVID-19 PROVISIONS: Due to precautions required to prevent the spread of COVID-19, all in-person visits were discontinued as of 3/25/2020. As of this date, DXA scans at both sites were discontinued. Analysis on existing data will continue, but no new DXA data will be collected.

Measure: Change in percent body fat - Randomization 1

Time: Baseline (-14 Days prior to Randomization 1 Visit), 3 Month (Measurement 2) Visit

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Description: Percent fat mass and percent fat free mass will be measured via a dual-energy x-ray absorptiometry (DXA) scan at the beginning and end of this three-and-a-half-month time period. COVID-19 PROVISIONS: Due to precautions required to prevent the spread of COVID-19, all in-person visits were discontinued as of 3/25/2020. As of this date, DXA scans at both sites were discontinued. Analysis on existing data will continue, but no new DXA data will be collected.

Measure: Change in percent body fat - Randomization 2

Time: 3 Month (Measurement 2) Visit, 6.5 Month (Measurement 3) Visit

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Description: Percent fat mass and percent fat free mass will be measured via a dual-energy x-ray absorptiometry (DXA) scan at the beginning and end of this three-and-a-half-month time period. COVID-19 PROVISIONS: Due to precautions required to prevent the spread of COVID-19, all in-person visits were discontinued as of 3/25/2020. As of this date, DXA scans at both sites were discontinued. Analysis on existing data will continue, but no new DXA data will be collected.

Measure: Change in percent body fat - Randomization 3

Time: 6.5 Month (Measurement 3) Visit, 10 Month (Measurement 4) Visit

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Description: Change in percent of time spent in a pre-defined range of relative euglycemia (for a person with Type 1 diabetes) during CGM wear time, will be assessed between the two weeks of wear from CGM insertion at Baseline Visit (-14 days) and the two weeks of wear from CGM insertion at Measurement Visit 2.

Measure: Difference in time spent within target blood glucose range - Randomization 1

Time: 2 weeks of wear from 3 Month (Measurement 2) Visit, 2 weeks of wear from 6.5 Month (Measurement 3) Visit

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Description: Change in percent of time spent in a pre-defined range of relative euglycemia (for a person with Type 1 diabetes) during CGM wear time, will be assessed between the two weeks of wear from CGM insertion at Measurement 2 Visit and from CGM insertion at Measurement 3 Visit.

Measure: Difference in time spent within target blood glucose range - Randomization 2

Time: 2 weeks of wear from 3 Month (Measurement 2) Visit, 2 weeks of wear from 6.5 Month (Measurement 3) Visit

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Description: Change in percent of time spent in a pre-defined range of relative euglycemia (for a person with Type 1 diabetes) during CGM wear time, will be assessed between the two weeks of wear from CGM insertion at Measurement 3 Visit and from CGM insertion at Measurement 4 Visit.

Measure: Difference in time spent within target blood glucose range - Randomization 3

Time: 2 weeks of wear from 6.5 Month (Measurement 3) Visit, 2 weeks of wear from 10 Month (Measurement 4) Visit

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Primary Outcomes

Measure: Change in Hemoglobin A1c

Time: Baseline and six months

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Secondary Outcomes

Measure: Change in fasting plasma glucose

Time: Baseline and six months

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Measure: Change in systolic blood pressure

Time: Baseline and six months

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Measure: Change in total-to-HDL-cholesterol ratio

Time: Baseline and six months

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Measure: Change in body weight

Time: Baseline and six months

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Other Outcomes

Measure: Change in insulin

Time: Baseline and six months

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Measure: Change in homeostasis model assessment of insulin resistance (HOMA-IR)

Time: Baseline and six months

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Measure: Change in diastolic blood pressure

Time: Baseline and six months

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Measure: Change in waist circumference

Time: Baseline and six months

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Description: Based on 10-year cardiovascular disease risk assessed by 2013 American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Score

Measure: Change in estimated cardiovascular disease risk

Time: Baseline and six months

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Primary Outcomes

Description: To evaluate safety and tolerability of CFZ533 in new onset T1DM.

Measure: Proportion of subjects with adverse events (AE)/serious adverse events (SAE) in treatment groups.

Time: at 16 months

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Description: To evaluate the treatment effect of CFZ533 on pancreatic beta cell function.

Measure: Stimulated C-peptide AUC by mixed meal tolerance test (MMTT).

Time: at 12 months

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Secondary Outcomes

Description: To evaluate the pharmacokinetics (PK) of CFZ533.

Measure: Free CFZ533 plasma concentration.

Time: at day 1

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Description: To evaluate the pharmacokinetics (PK) of CFZ533.

Measure: Free CFZ533 plasma concentration.

Time: at 1 week

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Description: To evaluate the pharmacokinetics (PK) of CFZ533.

Measure: Free CFZ533 plasma concentration.

Time: at 12 months

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Description: To evaluate the treatment effect of CFZ533 on full or partial remission.

Measure: Proportion of subjects with full or partial remission.

Time: at 12 months

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Description: To evaluate durability of effects of CFZ533 on pancreatic beta cell function.

Measure: Stimulated C-peptide AUC by MMTT.

Time: at 3 years

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Primary Outcomes

Measure: time sedentary measured via triaxial accelerometer

Time: 7 days

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Measure: average sedentary bout length measured via triaxial accelerometer

Time: 7 days

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Description: peak volume of oxygen consumption (VO2 peak) in ml/kg/min measured via graded exercise test

Measure: cardiorespiratory fitness

Time: 8-12 minutes

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Description: glucose infusion rate in mg/kg/min as measured via hyperinsulinemic-euglycemic clamp

Measure: insulin sensitivity

Time: 3 hours

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Measure: change in skeletal muscle deoxygenated hemoglobin concentration during single leg calf exercise measured via near-infrared spectroscopy

Time: 30 minutes

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Primary Outcomes

Description: Prevalence of severe forms among all COVID-19 patients with diabetes

Measure: Assess the prevalence of severe forms among hospitalized patients with diabètes and COVID-19

Time: 1 month

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Secondary Outcomes

Description: Use the body weight, type of diabetes, tglycemic control (HbA1C at admission), the comorbidities and complications associated with diabetes and finally the usual therapies.

Measure: describe the clinical and biological characteristics of hospitalized subjects with diabetes and COVID-19

Time: 1 month

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Description: death at 7 days after admission, hospital death and date of death, total length of hospitalization and discharge procedures, serious form requiring the use of artificial ventilation with tracheal intubation and date of use of this treatment, decision to limit

Measure: describe the prognosis of hospitalized subjects with diabetes and COVID-19

Time: 1 month

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Description: care service where the patient is taken care of, insulin therapy (IVSE or multi-injection) and dose of insulin required on D2 and D7

Measure: describe the care management of hospitalized subjects with diabetes and COVID-19

Time: 1 month

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Primary Outcomes

Description: Variation in HbA1c levels comparatively between groups after the period of social distancing measures.

Measure: Variation in HbA1c levels

Time: 4 months (or as long as the recommendation of social distancing measures remains)

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Secondary Outcomes

Description: Confirmation of coronavirus infection by rapid test

Measure: COVID-19 infection

Time: 4 months (or as long as the recommendation of social distancing measures remains)

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Description: Comparison of the lipid profile of the last year with the lipid profile after the intervention between the groups.

Measure: Variation in lipid profile

Time: 4 months (or as long as the recommendation of social distancing measures remains)

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Description: Comparison of the blood pressure level of the last consultation with the pressure after the intervention between the groups.

Measure: Variation in blood pressure levels

Time: 4 months (or as long as the recommendation of social distancing measures remains)

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Description: Evaluation of emotional distress associated with the routine of living with diabetes - B-PAID (Brazilian Problem Areas In Diabetes Scale)

Measure: Comparison of emotional distress associated with the routine of living with diabetes after intervention between groups

Time: 4 months (or as long as the recommendation of social distancing measures remains)

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Description: Evaluation of eating disorders - EAT - 26 SCALE (Teste de Atitudes Alimentares)

Measure: Comparison of eating disorders between groups

Time: 4 months (or as long as the recommendation of social distancing measures remains)

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Description: Evaluation of adherence to the proposed clinical treatment - SCI R (Self-Care Inventory - revised)

Measure: Comparison of adherence to the proposed clinical treatment between groups

Time: 4 months (or as long as the recommendation of social distancing measures remains)

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Description: Evaluation of minor psychiatric disorders - SRQ 20 (Self Report Questionnaire)

Measure: Comparison of minor psychiatric disorders between groups

Time: 4 months (or as long as the recommendation of social distancing measures remains)

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Description: Evaluation of sleep pattern changes - MSQ (Mini Sleep Questionnaire)

Measure: Comparison of sleep pattern changes between groups

Time: 4 months (or as long as the recommendation of social distancing measures remains)

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Primary Outcomes

Description: Clinical change is defined as 2 points reduction in the World Health Organization (WHO) Ordinal Scale for Clinical Improvement of COVID-19: 0 - No clinical or virological evidence of infection; 1 - No limitation of activities; 2 - Limitation of activities; 3 - Hospitalized, no oxygen therapy; 4 - Oxygen by mask or nasal prongs; 5 - Non-invasive ventilation or high-flow oxygen; 6 - Intubation and mechanical ventilation; 7 - Ventilation + additional organ support - pressors, renal replacement therapy, extracorporeal membrane oxygenation; 8 - Death.

Measure: Time to clinical change

Time: 28 days

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Secondary Outcomes

Measure: Percent of serious adverse events and premature discontinuation of treatment.

Time: 28 days

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Description: Percent of patients with a 2 points reduction in the World Health Organization (WHO) Ordinal Scale for Clinical Improvement of COVID-19.

Measure: Percent of patients with clinical improvement.

Time: 28 days

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Measure: Length of hospitalization.

Time: 28 days

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Measure: All-cause mortality.

Time: 28 days

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Measure: Percent of supplemental oxygen use.

Time: 28 days

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Measure: Supplemental oxygen-free days.

Time: 28 days

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Measure: Percent of mechanical ventilation use.

Time: 28 days

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Measure: Ventilator-free days.

Time: 28 days

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Measure: Percent of ICU admissions.

Time: 28 days

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Measure: ICU-free days.

Time: 28 days

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Measure: Percent of 50% decrease in C-reactive protein (CRP) levels

Time: Up to 28 days

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Measure: Time to virologic response, defined as no detection of SARS-CoV-2 in a PCR test.

Time: 28 days

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Primary Outcomes

Description: The number of days required to achieve a score of 0 for each symptom category. Resolution of symptoms: fever (time frame: 21 days) Fever based on a 0-3 scale: 0 = ≤98.6, 1 => 98.6- 100.6, 2 => 100.6 - 102.6, 3 => 102.6 Resolution of symptoms: cough (time frame: 21 days) Cough based on a 0-3 scale: 0 = no cough, 1 = mild, 2 = moderate, 3 = severe Resolution of symptoms: shortness of breath (time frame: 21 days) Shortness of breath based on a 0-3 scale: 0 = no shortness of breath, 1 = with moderate intensity exercise 2 = walking on a flat surface 3 = shortness of breath when dressing or doing daily activities Resolution of symptoms: fatigue (period: 21 days) Fatigue based on a 0-3 scale: 1 = mild fatigue, 2 = moderate fatigue, 3 = severe fatigue. Composite score that includes all symptoms: (time frame: 21 days) Total composite score of symptoms on days 5, 10, 15, and 21 of study supplementation.

Measure: Symptom resolution

Time: 21 days

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Secondary Outcomes

Description: Disease severity will be measured using a disease severity clinical event scale (assessed until day 21) Change from baseline in the patient's health status on an ordinal scale of 7 categories (time frame: days 3, 7, 14, 21) death Hospitalized, with invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, with non-invasive ventilation or high-flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, which does not require supplemental oxygen Not hospitalized, limitation of activities. Not hospitalized, without limitations in activities. Note: lower scores mean a worse result.

Measure: Cumulative incidence of disease severity

Time: 21 days

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Description: Differences in the number of patients who received complementary medications for diagnosis between the study arms.

Measure: Complementary drugs required

Time: 21 days

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Description: Differences in the number of patients in the study groups experiencing side effects of the supplements.

Measure: Side effects of supplementation

Time: 21 days

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Description: PCR analysis at day 0, 7th, 14th and 21th to measure and compare viral load

Measure: Duration of SARS-CoV-2 PCR positivity

Time: 21 days

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Description: Blood biochemical analysis at day 0, 3rd, 7th, 14th and 21th

Measure: Concentration of reactive protein c in peripheral blood

Time: 21 days

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Description: Number of Incidence of hospitalization

Measure: Incidence of hospitalization

Time: 21 days

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Description: Number of days of hospitalization

Measure: Duration (days) of hospitalization

Time: 21 days

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Description: Number of Incidences of mechanical ventilation supply per patient

Measure: Incidence of mechanical ventilation supply

Time: 21 days

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Description: Number of days with mechanical ventilation supply

Measure: Duration (days) of mechanical ventilation supply

Time: 21 days

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Description: Number of incidences of oxygen use

Measure: Incidence of oxygen use

Time: 21 days

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Description: Number of days of oxygen use per patient

Measure: Duration (days) of oxygen use

Time: 21 days

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Description: Number of death per group

Measure: Mortality rate

Time: 21 days

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Description: Number of days patient need to recover from disease

Measure: Time to return to normal activity

Time: 21 days

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Other Outcomes

Description: Change from baseline in serum cytokine IL-1 level by blood biochemical analysis at day 0, 3, 7, 14 and 21

Measure: Change from baseline in serum cytokine levels

Time: 21 days

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Description: Change from baseline in serum cytokine IL-6 level by blood biochemical analysis at day 0, 3, 7, 14 and 21

Measure: Change from baseline in serum cytokine levels

Time: 21 days

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Description: Change from baseline in serum cytokine TNF-α level by blood biochemical analysis at day 0, 3, 7, 14 and 21

Measure: Change from baseline in serum cytokine levels

Time: 21 days

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Description: Change from baseline in CCR5 receptor occupancy levels for Tregs and macrophages by blood biochemical analysis at day 0, 3, 7, 14 and 21

Measure: Change from baseline in CCR5 receptor occupancy levels for Tregs and macrophages

Time: 21 days

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Description: Change from baseline in CD3 +, CD4 + and CD8 + T cell counts by blood biochemical analysis at day 0, 3, 7, 14 and 21.

Measure: Change from baseline in CD3 +, CD4 + and CD8 + T cell counts

Time: 21 days

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Description: Change in liver function test (AST, ALT and TBIL) by blood biochemical analysis at day 0, 4, 7, 14 and 21.

Measure: Change in liver function test

Time: 21 days

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Description: Change in kidney function with eGFR rate by blood and urinary biochemical analysis at day 0, 4, 7, 14 and 21.

Measure: Change in kidney function test

Time: 21 days

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Description: Change in kidney function with creatine clearance rate by blood and urinary biochemical analysis at day 0, 4, 7, 14 and 21.

Measure: Change in kidney function test

Time: 21 days

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Description: Change in routine blood test red blood cells concentration by blood biochemical analysis at day 0, 4, 7, 14 and 21.

Measure: Change in routine blood test

Time: 21 days

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Description: Change in routine blood test white blood cell concentration by blood biochemical analysis at day 0, 4, 7, 14 and 21.

Measure: Change in routine blood test

Time: 21 days

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Description: Change in routine blood test D-dimer level by blood biochemical analysis at day 0, 4, 7, 14 and 21.

Measure: Change in routine blood test

Time: 21 days

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Description: Change in routine blood test fibrinogen level by blood biochemical analysis at day 0, 4, 7, 14 and 21.

Measure: Change in routine blood test

Time: 21 days

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Description: Change in myocardial enzyme CPK-MB by blood biochemical analysis at daty 0, 4, 7, 14 and 21

Measure: Change in myocardial enzymes

Time: 21 days

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Description: Change in myocardial enzymes troponins by blood biochemical analysis at daty 0, 4, 7, 14 and 21

Measure: Change in myocardial enzymes

Time: 21 days

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Primary Outcomes

Description: The within-subject effect of plasma glucose levels on left ventricular systolic function as measured by left ventricular ejection fraction (a pooled analysis of the hospitalisation cohort and ICU cohort)

Measure: Plasma glucose levels and left ventricular ejection fraction

Time: The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours).

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Secondary Outcomes

Description: Difference in the within-subject effect of plasma glucose levels on left ventricular systolic function as measured by left ventricular ejection fraction between patients with chronic hyperglycaemia prior to admission (HbA1c >53 mmol/mol) and with normoglycaemia prior to admission (HbA1c ≤53 mmol/l) (ICU cohort only)

Measure: Key secondary outcome: HbA1c, plasma glucose levels and left ventricular systolic function

Time: The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours).

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Description: The within-subject effect of plasma glucose levels on left ventricular systolic function as measured by strain analysis (a pooled analysis of the hospitalisation cohort and ICU cohort)

Measure: Plasma glucose levels and strain analysis

Time: The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours).

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Description: The within-subject effect of plasma glucose levels on left ventricular systolic function as measured by mitral annular systolic velocity (a pooled analysis of the hospitalisation cohort and ICU cohort)

Measure: Plasma glucose levels and mitral annular systolic velocity

Time: The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours).

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Description: Differences in the within-subject effect of plasma glucose levels on left ventricular systolic function as measured by left ventricular ejection fraction between the hospitalisation cohort, the ICU cohort with diabetes and the ICU cohort without diabetes, respectively

Measure: Plasma glucose levels and left ventricular ejection fraction (sub-group analysis)

Time: The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours).

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Description: Differences in the within-subject effect of plasma glucose levels on left ventricular systolic function as measured by strain analysis between the hospitalisation cohort, the ICU cohort with diabetes and the ICU cohort without diabetes, respectively

Measure: Plasma glucose levels and strain analysis (sub-group analysis)

Time: The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours).

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Description: Differences in the within-subject effect of plasma glucose levels on left ventricular systolic function as measured by mitral annular systolic velocity between the hospitalisation cohort, the ICU cohort with diabetes and the ICU cohort without diabetes, respectively

Measure: Plasma glucose levels and mitral annular systolic velocity (sub-group analysis)

Time: The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours).

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Description: Difference in the within-subject effect of plasma glucose levels on left ventricular systolic function as measured by strain analysis between patients with chronic hyperglycaemia prior to admission (HbA1c >53 mmol/mol) and with normoglycaemia prior to admission (HbA1c ≤53 mmol/l) (ICU cohort only)

Measure: HbA1c, Plasma glucose levels and strain analysis

Time: The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours).

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Description: Difference in the within-subject effect of plasma glucose levels on left ventricular systolic function as measured by mitral annular systolic velocity between patients with chronic hyperglycaemia prior to admission (HbA1c >53 mmol/mol) and with normoglycaemia prior to admission (HbA1c ≤53 mmol/l) (ICU cohort only)

Measure: HbA1c, Plasma glucose levels and mitral annular systolic velocity

Time: The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours).

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Description: Difference in whole blood coagulability and fibrinolysis as measured by TEG between patients with and without diabetes at time of admission to the ICU (ICU cohort only)

Measure: Diabetes status and whole blood coagulability and fibrinolysis

Time: At time of admission to the ICU (max. 24 hours after admission to the ICU)

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Description: Difference in change in whole blood coagulability and fibrinolysis as measured by TEG between patients with and without diabetes treated at the ICU (ICU cohort only)

Measure: Diabetes status and change in whole blood coagulability and fibrinolysis during ICU stay

Time: From first until last assessment during ICU stay (max. 24 hours).

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Description: The prognostic value of cardiac function and TEG on the following patient outcomes 1) need for treatment in the ICU (hospitalisation cohort only) 2) need for respirator treatment (hospitalisation cohort only) 3) COVID-19 related death

Measure: Prognostic value of TEG analysis

Time: From time of admission and until four weeks after admission

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Description: The prognostic value of cardiac function on the following patient outcomes 1) need for treatment in the ICU (hospitalisation cohort only) 2) need for respirator treatment (hospitalisation cohort only) 3) COVID-19 related death

Measure: Prognostic value of cardiac function

Time: From time of admission and until four weeks after admission

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Description: Difference in cardiac damage as measured by high-sensitivity troponin (hs-troponin) between patients with and without diabetes admitted to the ICU (ICU cohort only)

Measure: Diabetes status and high-sensitivity troponins

Time: At the time of admission to the ICU (max. 24 hours after admission to the ICU)

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Description: Difference in change in cardiac damage as measured by high-sensitivity troponin (hs-troponin) between patients with and without diabetes admitted to the ICU (ICU cohort only)

Measure: Diabetes status and change high-sensitivity troponins

Time: From first until last assessment during ICU stay (max. 24 hours)

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Primary Outcomes

Description: Assess the prevalence of diabetes among hospitalized patients with Covid-19 in Area of Tlemcen

Measure: Prevalence of diabetes among all hospitalized COVID-19

Time: 3 months

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Description: Describe the clinical and biological characteristics of hospitalized subjects with diabetes and COVID-19

Measure: Diabetes-related factors risk

Time: 3 months

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Primary Outcomes

Description: TIR is presented in percent of time in which the participants' glucose values are in different glucose ranges.

Measure: Time In Range (TIR) for blood glucose

Time: 1-2 weeks

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Secondary Outcomes

Description: Saved patient-personnel contacts related to blood glucose measurements, incl. time healthcare providers spent on diabetes related tasks and PPE related tasks, during the patients' hospitalization.

Measure: Saved patient-personnel contacts related to blood glucose measurements.

Time: 1-2 weeks

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Description: Additional glucose outcomes based on data from Dexcom G6 are for example Time Above Range (TAR), Time Below Range (TBR), average glucose, variance in glucose (CV), etc.

Measure: Glucose variations during hospitalization

Time: 1-2 weeks

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Description: That is: Tablet-based and insulin-based regimens and number of times that sliding scale insulin (including dose of insulin) has been administered for each patient.

Measure: Blood glucose lowering interventions

Time: 1-2 weeks

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Description: Number of techincal errors during the sensors lifetime.

Measure: CGM sensor performance

Time: 1-2 weeks

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Description: Hospital death (yes/no), length of stay at hospital, need for respiratory support (yes/no) and intensive care (yes/no), recovered vs. fatal (death within 60 days from admission).

Measure: Course of hospital stay.

Time: 1-2 weeks

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Primary Outcomes

Description: Change in frailty measured on a scale using a frailty score (0, 1, 2, 3, 4,or 5), with higher scores out of 5 representing greater frailty. Assessments used for scoring include 1) self reported weight loss, 2) self-reported exhaustion 3) low physical activity based on the Minnesota Leisure Time Physical Activity Questionnaire (MLTPAQ) 4) Handgrip strength 5) 10 foot walk pace

Measure: Frailty Scale

Time: Baseline to 6 months

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Secondary Outcomes

Description: Change in HbA1c measured over the study period

Measure: Glycated hemoglobin (HbA1c)

Time: Baseline to 6 months

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Description: For PROMIS measures, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function). Thus a score of 60 is one standard deviation above the average referenced population. This could be a desirable or undesirable outcome, depending upon the concept being measured.

Measure: Patient-Reported Outcomes Measurement Information System (PROMIS)

Time: Baseline to 6 months

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Description: The study team will administer the Short Physical Performance Battery (SPPB)69 to assess three lower extremity tasks; 1) standing balance (ability to stand with the feet together in side-by-side, semi-and full-tandem positions for 10 seconds each); 2) a 4-meter walk to assess usual gait speed; 3) time to complete 5 repeated chair stand. Each of the 3 performance measures is assigned a score ranging from 0 (inability to perform the task) to 4 (the highest level of performance) and summed to create a score ranging from 0 to 12 (best). The SPPB is sensitive to change over time

Measure: Short Physical Performance Battery (SPPB)

Time: Baseline to 6 months

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Primary Outcomes

Description: HbA1c levels before and after the lockdown period. A 3 months period is required between the 2 values.

Measure: Compare glycated hemoglobin levels of patients with diabetes from the University Hospital of Nancy between the period preceding and following the lockdown related to the COVID-19 pandemic.

Time: 6 months period prior to lockdown - 6 weeks period following the end of the lockdown

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Secondary Outcomes

Description: Use type of diabetes, BMI, lipid profile, micro- and macro-comorbidities and usual therapies from medical records

Measure: Describe the clinical and biological characteristics of patients with diabetes followed in routine care at the University Hospital of Nancy

Time: 6 weeks period following the end of the lockdown

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Description: Use BMI, lipid profile, renal and hepatic function from medical records

Measure: Describe the change from baseline of biological and clinical parameters of patients with diabetes followed in routine care at the University Hospital of Nancy between the period preceding and following the lockdown.

Time: 6 months period prior to lockdown - 6 weeks period following the end of the lockdown

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Description: Ketosis, Ketoacidosis, severe hypoglycemia, COVID-19 infection, hospitalization

Measure: Describe the proportion of patients who presented with one or more significant clinical event during the lockdown.

Time: 6 weeks period following the end of the lockdown

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Description: Proportion of patients who forgot and/or discontinued one or several medication(s), medication involved, duration and frequency of omission/discontinuation

Measure: Describe the proportion of patients who forgot and/or discontinued one or several medication(s) during the lockdown.

Time: 6 weeks period following the end of the lockdown

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Description: Porportion of patients who modified their usual level of physical activity and/or their consumption of alcohol and/or tobacco

Measure: Describe the proportion of patients who changed their lifestyle's habits during the lockdown.

Time: 6 weeks period following the end of the lockdown

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Description: Proportion of patients who consulted their GP, a specialist physician, pharmacist, biologist, nurse, paramedic, other healthcare professional; type of visit (regular face to face, telemedecine); method for prescription renewal; reason for delay in care; hospitalization (excluding for COVID-19)

Measure: Describe healthcare consumption of patients with diabetes during the lockdown.

Time: 6 weeks period following the end of the lockdown

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Description: Proportion of patients who (1) was tested for SARS-CoV-2 by PCR, (2) developped COVID-19 confirmed by PCR and (3) was hospitalized due to the severity of COVID-19.

Measure: Describe the proportion of patients who (1) was tested for SARS-CoV-2 by PCR, (2) developped COVID-19 confirmed by PCR and (3) was hospitalized due to the severity of COVID-19.

Time: 6 weeks period following the end of the lockdown

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Primary Outcomes

Description: Blood glucose was expressed in mg/dl and was determined by standard techniques.

Measure: Glucose

Time: One week after the end of the lockdown period

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Description: HbA1c was expressed as percentage or mmol/l and was determined by standard techniques.

Measure: HbA1c

Time: One week after the end of the lockdown period

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Description: Complete lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol, Triglcerydes) were expressed in mg/dl or mmol/l and were determined by standard techniques.

Measure: Lipid profile

Time: One week after the end of the lockdown period

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Primary Outcomes

Measure: the area under the stimulated C-peptide response curve

Time: over the first 2 hours of a MMTT [ mixed meal tolerance test] at 12 months post treatment

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Secondary Outcomes

Measure: the area under the stimulated C-peptide response curve

Time: over teh first 2 hours of a MMTT at baseline, 3, 6 and 12 months

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Measure: DBS [dry blood spot] C-peptide measurements

Time: at all observation times

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Measure: CD4 positive T cells and CD8 positive T cells

Time: over 12 months

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Measure: HBA1c

Time: over 12 months

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Measure: insulin require months

Time: over 12 months

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Measure: T1D-associated autoantibodies ( GADA [glutamic acid decarboxylase antibodies], IAA [insulin auto-antibodies], IA-2A [IA-2 antibodies] and ZnT8A

Time: over 12 months

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Measure: CGM [continuous glucose monitoring] measurements ( time in range, time above time below)

Time: over 12 months

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Primary Outcomes

Description: Treatment and placebo will be compared on the basis of the unmatched win-ratio approach of Pocock. When comparing two patients, the winner will be determined by the first component in which the two patients differ (4 weeks after randomization): longer survival time longer ventilation-free time longer ICU-free time shorter hospitalization time If there is no difference between treatment and Placebo: the win ratio is 1. If there is a difference between treatment and Placebo: the win ratio is not 1.

Measure: unmatched win ratio after treatment with canakinumab compared to Placebo (composite endpoint)

Time: within 4 weeks after treatment with canakinumab or placebo

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Secondary Outcomes

Description: Time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever comes first. "The seven-category ordinal scale consists of the following categories: not hospitalized with resumption of normal activities; not hospitalized, but unable to resume normal activities; hospitalized, not requiring supplemental oxygen; hospitalized, requiring supplemental oxygen; hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; hospitalized, requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or both; and death"

Measure: Time to clinical improvement

Time: From randomization up to 4 weeks

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Description: Death rate during the 4-week period after study treatment

Measure: Death rate

Time: 4 weeks

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Description: Admission to the intensive care unit from the medical ward during the 4-week period after study treatment

Measure: Admission to intensive care unit (ICU)

Time: 4 weeks

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Description: Secondary worsening of disease (i.e., development of Acute respiratory distress Syndrome (ARDS), increase of oxygen demand after 72h of treatment)

Measure: Secondary worsening of disease

Time: 4 weeks

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Description: Prolonged hospital stay > 3 weeks

Measure: Prolonged hospital stay

Time: >3 weeks

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Description: Ratio to baseline in the glycated hemoglobin

Measure: Change in ratio to baseline in the glycated hemoglobin

Time: Baseline, Day 29 and Day 90

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Description: Ratio to baseline in the fasting glucose

Measure: Change in ratio to baseline in the fasting glucose

Time: Baseline, Day 29

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Description: Ratio to baseline in the fasting insulin

Measure: Change in ratio to baseline in the fasting insulin

Time: Baseline, Day 29

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Description: Ratio to baseline in the fasting c-peptide

Measure: Change in ratio to baseline in the fasting c-peptide

Time: Baseline, Day 29

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Description: Ratio to baseline in the C-reactive protein (CRP)

Measure: Ratio to baseline in the C-reactive protein (CRP)

Time: Baseline, Day 29 and Day 90

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Description: Ratio to baseline in the D-dimer

Measure: Change in ratio to baseline in the D-dimer

Time: Baseline, Day 29

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Description: Ratio to baseline in the Natriuretic peptide (NTproBNP)

Measure: Change in ratio to baseline in the Natriuretic peptide (NTproBNP)

Time: Baseline, Day 29 and Day 90

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Description: Ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)

Measure: Change in ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)

Time: Baseline, Day 29 and Day 90

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Description: Type of antidiabetic treatment at Day 29

Measure: Type of antidiabetic treatment at Day 29

Time: Day 29

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Description: Number of antidiabetic treatment at Day 29

Measure: Number of antidiabetic treatment at Day 29

Time: Day 29

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Description: Type of antidiabetic treatment at three months

Measure: Type of antidiabetic treatment at three months

Time: Month 3

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Description: Number of antidiabetic treatment at three months

Measure: Number of antidiabetic treatment at three months

Time: Month 3

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Primary Outcomes

Description: Change in HbA1c from baseline to 3 month after the lockdown

Measure: Impact of COVID-19 pandemic and lockdown on glycemic control among a sample of Egyptian children and adolescents with type 1 diabetes

Time: 12 weeks

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Secondary Outcomes

Description: Change in total insulin dosage from baseline to 3 month after the lockdown

Measure: Impact of COVID-19 pandemic and lockdown on insulin dosage among a sample of Egyptian children and adolescents with type 1 diabetes

Time: 12 weeks

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Primary Outcomes

Description: Number of patients receive pioglitazone treatment during their hospital stay who receive support with mechanical ventilation, enter the ICU and / or die.

Measure: Patients treated with pioglitazone, together with conventional treatment for COVID-19 infection, who during their admission evolve towards the need to receive support with mechanical ventilation, enter the ICU and / or die.

Time: Through hospitalization period, an average of 10-20 days until hospital discharge

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Secondary Outcomes

Description: Proportion of patients who develop heart failure or adverse reaction associated with treatment.

Measure: Incidence of pioglitazone treatment-Emergent Adverse Events in patients with DM2 and symptomatic SARS-CoV-2 infection.

Time: Everyday through hospitalization period, an average of 10-20 days until hospital discharge

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Description: Changes in this inflammation parameter: C-reactive protein (in mg/dl)

Measure: Biomarker analysis: systemic inflammation parameters during the administration of pioglitazone treatment.

Time: Each 48 hours through hospitalization period, an average of 10-20 days until hospital discharge

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Description: Changes in this inflammation parameter: D-dimer (in μg/mL)

Measure: Biomarker analysis: systemic inflammation parameters during the administration of pioglitazone treatment.

Time: Each 48 hours through hospitalization period, an average of 10-20 days until hospital discharge

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Description: Changes in this inflammation parameter: ferritin (in ng/mL)

Measure: Biomarker analysis: systemic inflammation parameters during the administration of pioglitazone treatment.

Time: Each 48 hours through hospitalization period, an average of 10-20 days until hospital discharge

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Description: Changes in this inflammation parameter: creatine kinase (CK) (in mg/dL)

Measure: Biomarker analysis: systemic inflammation parameters during the administration of pioglitazone treatment.

Time: Each 48 hours through hospitalization period, an average of 10-20 days until hospital discharge

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Description: Changes in this inflammation parameter: number of lymphocytes (in μL)

Measure: Biomarker analysis: systemic inflammation parameters during the administration of pioglitazone treatment.

Time: Each 48 hours through hospitalization period, an average of 10-20 days until hospital discharge

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Primary Outcomes

Description: complications and comorbidities associated with diabetes

Measure: Clinical characteristic of pediatric and adolescent patients with type 1 diabetes hospitalized with COVID -19.

Time: 4 months

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Description: Acute phase reactants

Measure: Laboratory characteristic of pediatric and adolescent patients with type 1 diabetes hospitalized with COVID -19.

Time: 4 months

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Description: Intensive care admission

Measure: Prognosis of pediatric and adolescent patients with type 1 diabetes hospitalized with COVID -19.

Time: 4 month

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Secondary Outcomes

Description: Incidence of new onset type 1 diabetes among confirmed cases of Covid-19 infection among children and adolescents

Measure: Incidence of new onset type 1 diabetes among confirmed cases of Covid-19 infection among children and adolescents

Time: 4 months

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Description: Impact of Covid-19 pandemic on presentation of diabetes and its acute complications among pediatric and adolescent patients with type 1 diabetes

Measure: Presentation of diabetes and its acute complications among pediatric and adolescent patients with type 1 diabetes during COVID-19 Pandemic in Egypt

Time: 4 month

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Primary Outcomes

Description: to assess risk of intensive care unit admission and/or death among COVID-19 inpatients

Measure: prevalence of intensive care unit admission and/or in-hospital mortality among COVID-19 inpatients

Time: february 23 to march 31, 2020

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Secondary Outcomes

Description: to compare risk of death among inpatients in presence or absence of diabetes

Measure: prevalence of death among COVID-19 inpatients with and without diabetes

Time: february 23 to march 31, 2020

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Description: to compare intensive care unit admission among inpatients in presence or absence of diabetes

Measure: prevalence of intensive care unit admission among COVID-19 inpatients with and without diabetes

Time: february 23 to march 31, 2020

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Description: to identify socio-demographic as predictors of severe prognosis (death or intensive care unit admission) during hospitalization

Measure: demographic and clinical characteristics (age,gender, comorbidity status) and death and/or intensive care unit admission during hospitalization

Time: february 23 to march 31, 2020

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Description: to identify laboratory variables as predictors of severe prognosis (death or intensive care unit admission) during hospitalization

Measure: laboratory parameters (glycated hemoglobin, glucose at admission, renal and liver function markers, blood count, inflammatory markers, hemostasis) and death and/or intensive care unit admission during hospitalization

Time: february 23 to march 31, 2020

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Description: to identify pharmacological therapies as predictors of severe prognosis (death or intensive care unit admission) during hospitalization

Measure: pharmacological therapies and death and/or intensive care unit admission during hospitalization

Time: february 23 to march 31, 2020

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Description: to compare total length of hospitalization in patients with or without diabetes

Measure: number of days of hospitalization in patients with and without diabetes

Time: february 23 to march 31, 2020

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Primary Outcomes

Description: The change from baseline in glucose AUC(0-4) will be analysed using a mixed model repeated measures (MMRM) with baseline included as covariate.

Measure: Change in glucose AUC(0-4) versus baseline compared to prednisolone following a standardised MMTT

Time: On Days -1, 4, 27, and 31

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Secondary Outcomes

Description: The mean daily glucose will be analysed using a MMRM analysis with baseline as covariate.

Measure: Mean daily glucose at 48 - 72 hours treatment as determined from multiple measures via the Continuous Glucose Monitoring (CGM) system

Time: On Days -2, 3, 26 and 30

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Description: The mean daily glucose will be analysed using an MMRM analysis with baseline as covariate.

Measure: Rise in mean daily glucose over 24-hour periods from start of IMP dosing (0 - 24 hours, 24 - 48 hours, 48 - 72 hours)

Time: On Days 1, 2, 3, 28, 29, 30

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Description: Pharmacodynamic effects of AZD9567 will be evaluated as compared to prednisolone.

Measure: Change from baseline in fasting glucose

Time: On Days -1, 4, 27, and 31

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Description: Effects on insulin, glucagon, GLP-1 and GIP of AZD9567 following MMTT in comparison to prednisolone will be assessed.

Measure: Change from baseline AUC(0-4) on hormones related to glucose homeostasis

Time: On Days -1, 4, 27, and 31

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Description: Pharmacodynamic effects of AZD9567 on glucose homeostasis through a MMTT in comparison to prednisolone will be assessed.

Measure: Change from baseline in AUC(0-4) on C-peptide

Time: On Days -1, 4, 27, and 31

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Description: Pharmacodynamic effects of AZD9567 on derived measures of beta cell function from the MMTT compared to prednisolone will be evaluated.

Measure: MMTT derived first phase insulin response

Time: On Days -1, 4, 27, and 31

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Description: The concentration of potassium in urine will be measured over 24 hours.

Measure: 24-hour potassium concentration

Time: On Days -1, 3, 27 and 30

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Description: The concentration of sodium in urine will be measured over 24 hours.

Measure: 24-hour sodium concentration

Time: On Days -1, 3, 27 and 30

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Description: AUClast will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

Measure: Area under the plasma concentration versus time curve from zero to the last quantifiable concentration (AUClast)

Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

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Description: AUC(0-24) will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

Measure: Area under the plasma concentration versus time curve from zero to 24 hours post-dose [AUC(0-24)]

Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

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Description: AUC(0-6) will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

Measure: Area under the plasma concentration versus time curve from zero to 6 hours post-dose [AUC(0-6)]

Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

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Description: Cmax will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

Measure: Maximum observed drug concentration (Cmax)

Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

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Description: Tmax will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

Measure: Time to reach maximum observed drug concentration (tmax)

Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

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Description: t½λz will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

Measure: Terminal elimination half-life (t½λz)

Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

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Description: CL/F will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

Measure: Apparent total body clearance of drug from plasma after extravascular (CL/F)

Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

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Description: Vz/F will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

Measure: Apparent volume of distribution following extravascular administration (Vz/F)

Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

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Description: Relationship between AZD9567 exposure and inhibition of LPS-stimulated TNFα release for high and low dose comparison (Cohort 1 and Cohort 2) will be assessed.

Measure: TNFα concentrations

Time: On Days 3 and 30 (Pre-dose, Post-dose 1, 2, 4, 8, 12, and 24 hours

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Description: Pharmacodynamic effects of AZD9567 will be evaluated following a MMTT compared to prednisolone.

Measure: Change in free fatty acids

Time: On Days -1, 4, 27, and 31

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Description: Pharmacodynamic effects of AZD9567 on derived measures of beta cell function from the MMTT compared to prednisolone will be evaluated.

Measure: Homeostatic model assessment- insulin resistance (HOMA-IR)

Time: On Days -1, 4, 27, and 31

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Description: Pharmacodynamic effects of AZD9567 on derived measures of beta cell function from the MMTT compared to prednisolone will be evaluated.

Measure: HOMA-insulin sensitivity

Time: On Days -1, 4, 27, and 31

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Description: Pharmacodynamic effects of AZD9567 on derived measures of beta cell function from the MMTT compared to prednisolone will be evaluated.

Measure: Modified Matsuda index

Time: On Days -1, 4, 27, and 31

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Description: Safety and tolerability will be assessed using variables like AEs/SAEs, vital signs, ECGs, changes in clinical chemistry/haematology parameters, morning serum cortisol, and adrenocorticotropic hormone.

Measure: Safety and tolerability of AZD9567 by assessing the number of participants with adverse events

Time: From screening up to 79 days

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Primary Outcomes

Description: Physical activity level using International Physical Activity Questionnaire - Short Form (IPAQ-SF) will be evaluated.

Measure: Physical activity level

Time: Five minutes

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Description: Quality of life using Short Form Health Survey (SF-36) will be evaluated.

Measure: General Quality of life

Time: Ten minutes

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Secondary Outcomes

Description: Depression using Hospital Anxiety and Depression Scale will be evaluated.

Measure: Depression

Time: Three minutes

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Description: Anxiety using Hospital Anxiety and Depression Scale will be evaluated.

Measure: Anxiety

Time: Three minutes

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Description: It will be questioned how many times patients have had hypoglycemic attacks (<4 mmol/L and common symptoms) in the last 7 days.

Measure: Self-reported hypoglycemia

Time: Last seven day

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Description: Loneliness using UCLA Loneliness Scale Short Form (ULS-8) will be evaluated.

Measure: Loneliness

Time: Three minutes

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Description: Hypoglisemia fear using Hypoglisemia Fear Survey (HFS) will be evaluated.

Measure: Hypoglisemia fear

Time: Five minutes

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Description: Dyspnea during daily life activites using Modified Medical Research Dyspnea Scale will be evaluated.

Measure: Dyspnea

Time: Two minutes

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Primary Outcomes

Description: Death due to diabetes-related complications or otherwise

Measure: All-cause mortality

Time: during 3months of lockdown

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Secondary Outcomes

Description: %age of participants with one or more symptoms of fever, sore throat, cough, dyspnoea

Measure: COVID-19 illness

Time: During 3months of lockdown

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Primary Outcomes

Description: pmol*h/L

Measure: AUCIco,0-inf,SD, Area under the serum insulin icodec concentration-time curve after a single dose

Time: From 0 hours until infinity after trial product administration (Day 1)

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Secondary Outcomes

Description: pmol/L

Measure: Cmax,Ico,SD, Maximum observed serum insulin icodec concentration after a single dose

Time: From 0 hours until last measurement time after trial product administration (Day 1)

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Description: hours

Measure: tmax,Ico,SD, Time to maximum observed serum insulin icodec concentration after a single dose

Time: From 0 hours until last measurement time after trial product administration (Day 1)

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Primary Outcomes

Description: The Electronic Medical Record (EMR) will be used to identify readmissions during each patient's unique follow up period. Unadjusted between group differences will first be analyzed by comparing proportion of patients with any hospital readmissions within the 30-day period by a Fisher's exact test. Followup analyses will be conducted using multiple logistic regression models to account for gender, ethnicity, race, comorbid conditions including COVID-19, medication use, and baseline glycemic control, in addition to study arm, as fixed effects in predicting the primary outcome, rate of readmissions within 30-days. We do not anticipate missing data for covariates included in regression models since demographic data will be captured directly from the EMR, and baseline glycemic control (i.e. HbA1c at hospital admission) and COVID-19 diagnosis will be determined during the admission of study enrollment.

Measure: Readmission rate (30-days)

Time: 30-days

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Description: Additional metrics of glycemic control will be captured for each study participant from the EMR including HbA1c at 90-days post-discharge. Unadjusted group mean differences in HbA1c will be assessed with a students t-test, followed by multiple linear regression analysis controlling for baseline HbA1c (at time of initial admission), as well as covariates including gender, ethnicity, race, comorbid conditions including COVID-19, and medication/steriod use, in addition to study arm, as fixed effects in predicting HbA1c at 90 days.

Measure: Glycosylated Hemoglobin (HbA1c)

Time: Baseline, 90-days

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Secondary Outcomes

Description: Diabetes distress will be measured using the Diabetes Distress Scale (DDS); range 1-6, with higher scores indicating worse outcomes/greater diabetes-related emotional stress. The survey will be administered immediately post enrollment, prior to randomizing, and during the 90-day follow-up visit. Measures will be compared between groups by t-tests at each time point.

Measure: Diabetes Distress Scale

Time: Baseline, 90-days

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Description: Research assistants will deliver the COVID-19 Patient Survey (PhenixToolkit) to each participant at their 90-day follow up to obtain their COVID-19 diagnosis status to determine whether any new infections occurred in the 90-day post-discharge time frame. Additional questions in the survey will be used for descriptive analyses to characterize infections. Differences in proportions of patients experiencing new infections per group (i.e. patients who were negative at discharge but had a self-reported positive test within 90 days) will be compared by Fisher's exact tests.

Measure: COVID-19 Patient Survey

Time: 90-days

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Description: Summary of Diabetes Self-Care Activities (SDSCA; range 0-7, with higher scores indicating better outcomes/greater adherence to diabetes self-management behaviors) will be administered immediately post enrollment, prior to randomizing, and during the 90-day follow-up visit. Measures will be compared between groups by t-tests at each time point.

Measure: Summary of Diabetes Self-Care Activities Survey

Time: Baseline, 90-days

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Description: Patient-Reported Outcomes Measurement Information System (PROMIS) Global-10 (range 0-100, with higher scores reflecting better outcomes/higher quality of life) will be administered immediately post enrollment, prior to randomizing, and during the 90-day follow-up visit. Measures will be compared between groups by t-tests at each time point.

Measure: PROMIS Quality of Life Scale

Time: Baseline, 90-days

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Description: Knowledge, Attitudes and Practices Toward COVID-19 Survey (range 0-12, with higher scores reflecting better knowledge of COVID-19) will be administered immediately post enrollment, prior to randomizing, and during the 90-day follow-up visit. Measures will be compared between groups by t-tests at each time point.

Measure: Knowledge, Attitudes and Practice Toward COVID-19 Survey

Time: Baseline, 90-days

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Description: Socio-Economic Status (SES), nativity, duration of US residence, Marital status, depressive symptoms and healthcare utilization will be measured immediately post enrollment, prior to randomizing.

Measure: Demographics Questionnaire

Time: Baseline

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Other Outcomes

Description: Exploratory analyses will be conducted similarly to our Primary Outcome. The EMR will be used to identify readmissions during each patient's unique follow up period. Unadjusted between group differences will first be analyzed by comparing proportion of patients with any hospital readmissions within the 90-day period by a Fisher's exact t-test. Followup analyses will be conducted using multiple logistic regression models to account for gender, ethnicity, race, comorbid conditions including COVID-19, medication use, and baseline glycemic control, in addition to study arm, as fixed effects in predicting the exploratory outcome, rate of readmissions within 90-days.

Measure: Readmission Rate (90-days)

Time: 90-days

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Primary Outcomes

Description: The time between admission to hospital and discharge

Measure: Duration of Hospitalisation

Time: 1 year

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Description: The admission of hospitalized patients to the intensive care unit.

Measure: The need for ICU

Time: 1 year

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Description: Mortality rates of patients

Measure: Mortality

Time: 1 year

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Description: The presence of lung involvement on thorax CT

Measure: Lung involvement

Time: 1 year

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Primary Outcomes

Description: the change in A1c levels

Measure: A1c

Time: 6 months (3 months before and after COVID-19

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Primary Outcomes

Description: The primary outcome in this study is feasibility, specifically process outcomes. This includes assessing recruitment number

Measure: Feasibility - Recruitment Numbers

Time: Through the study completion, an average of 4 months

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Description: The primary outcome in this study is feasibility, specifically process outcomes. This includes participant characteristics

Measure: Feasibility - Participant characteristics

Time: up to 8-weeks

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Description: The primary outcome in this study is feasibility, specifically process outcomes. This includes participant retention rate (e.g., defined by time between first and last visit)

Measure: Feasibility - Participant Engagement (retention rate)

Time: up to 8-weeks

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Description: The primary outcome in this study is feasibility, specifically process outcomes. This includes intensity (e.g., number of session participants attend)

Measure: Feasibility - Participant Engagement (intensity)

Time: up to 8-weeks

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Description: The primary outcome in this study is feasibility, specifically process outcomes. This includes drop out (consented/enrolled but did not attend first one-on-one)

Measure: Feasibility - Participant Engagement (drop out)

Time: up to 8-weeks

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Description: The primary outcome in this study is feasibility, specifically process outcomes. This includes the amount of time a coach spends per interaction

Measure: Feasibility - Delivery of Intervention (Time with coach)

Time: up to 8-weeks

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Description: The primary outcome in this study is feasibility, specifically process outcomes. This includes the mode of the interaction (i.e., virtual, telephone or both)

Measure: Feasibility - Delivery of Intervention (Mode of interaction)

Time: up to 12-weeks

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Description: The primary outcome in this study is feasibility, specifically process outcomes. This includes what strategies are used by the coach (i.e., educational, psychosocial support, behaviour modifications, or case management/monitoring)

Measure: Feasibility - Delivery of Intervention (Coach strategies)

Time: up to 12-weeks

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Secondary Outcomes

Description: The secondary outcome consists of study participant experience/satisfaction.

Measure: Study Participant experience and satisfaction via semi-structured interview

Time: up to 8-weeks

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Description: The secondary outcome consists of Care Coordinator experience and satisfaction.

Measure: Care Coordinator experience and satisfaction via semi-structured interview

Time: up to 8-weeks

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Description: The secondary outcome consists of Virtual Care Team experience and satisfaction.

Measure: Virtual Care Team experience and satisfaction via semi-structured interview

Time: up to 8-weeks

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Other Outcomes

Description: The exploratory outcomes will include Health Behaviour metrics via International Physical Activity Questionnaire). Individual scores per question, the higher the score means the higher the level of physical activity.

Measure: Exploratory Outcome - Health Behaviour metrics (physical activity)

Time: up to 4-weeks

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Description: The exploratory outcomes will include Health Behaviour metrics (via Mediterranean Diet Adherence Screener Modified (MEDAS modified)

Measure: Exploratory Outcome - Health Behaviour metrics (diet)

Time: up to 4-weeks

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Description: The exploratory outcomes will include Health Behaviour metrics (via readiness to change ruler (smoking, alcohol, nutrition, physical activity). Minimum score: 0; maximum score: 10; higher score represented a better outcome.

Measure: Exploratory Outcome - Health Behaviour metrics (confidence/importance to change behaviour)

Time: up to 12-weeks

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Description: The exploratory outcomes will include substance use (via GAINS-SS (Global Appraisal of Individual Needs- Short Screener). Minimum score: 0; maximum score: 20; higher score represented a worse outcome.

Measure: Exploratory Outcome - Substance Use (GAINS-SS)

Time: up to 12-weeks

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Description: The exploratory outcomes will include substance use (Alcohol Use Disorders Identification Test (AUDIT); Minimum score: 0; maximum score: 40; higher score represented a worse outcome.

Measure: Exploratory Outcome - Substance Use (alcohol)

Time: up to 12-weeks

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Description: The exploratory outcomes will include substance use (via heaviness of smoking index - 2 items out of Fagerstrom test for nicotine dependence (FTND)); Minimum score: 0; maximum score: 6; higher score represented a worse outcome.

Measure: Exploratory Outcome - Substance Use

Time: up to 12-weeks

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Description: The exploratory outcomes will include Mental Health measures (via Patient Health Questionnaire (PHQ-9)). Minimum score: 0; maximum score: 27; higher score represented a worse outcome.

Measure: Exploratory Outcome - Mental Health (depression)

Time: up to 12-weeks

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Description: The exploratory outcomes will include Mental Health measures via Generalized Anxiety Disorder-7 (GAD-7). Minimum score: 0; maximum score: 21; higher score represented a worse outcome.

Measure: Exploratory Outcome - Mental Health (Anxiety)

Time: up to 12-weeks

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Description: The exploratory outcomes will include Mental Health measures via Diabetes awareness and insight scale. Minimum score: 0; maximum score: 10; higher score represented a better outcome.

Measure: Exploratory Outcome - Mental Health (Diabetes awareness/insight)

Time: up to 12-weeks

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Description: The exploratory outcomes will include Mental Health measures via Diabetes Distress Scale. Minimum score: 0; maximum score: 6; higher score represented a worse outcome.

Measure: Exploratory Outcome - Mental Health (Diabetes Distress)

Time: up to 12-weeks

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Description: The exploratory outcomes will include Mental Health measures via perceived stress scale (PSS). Minimum score: 0; maximum score: 40; higher score represented a worse outcome (i.e., higher perceived stress).

Measure: Exploratory Outcome - Mental Health (Stress)

Time: up to 12-weeks

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Description: The exploratory outcomes will include quality of life (via European Quality of Life - 5 Dimensions scale - EQ5D). Minimum score: 0; maximum score: 100; higher score represented a better outcome.

Measure: Exploratory Outcome - Quality of Life

Time: up to 12-weeks

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Description: The exploratory outcomes will include quality of life (via Verona satisfaction scale). Minimum score: 0; higher score represented a better outcome.

Measure: Exploratory Outcome - Quality of Life

Time: up to 12-weeks

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Description: self-report

Measure: Exploratory Outcome - Waist circumference

Time: up to 12-weeks

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Description: self-report

Measure: Exploratory Outcome - BMI (height/weight)

Time: up to 12-weeks

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Description: self-report

Measure: Exploratory Outcome - Blood pressure

Time: up to 12-weeks

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Description: list

Measure: Exploratory Outcome - Current medication

Time: up to 12-weeks

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Description: Hemoglobin A1C levels

Measure: Exploratory Outcome - Blood work

Time: up to 12-weeks

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Description: Brief Pain Inventory-sf. Minimum score: 0; maximum score: 10; higher score represented a worse outcome (i.e., more pain).

Measure: Exploratory Outcome - Pain

Time: up to 12-weeks

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Description: months

Measure: Exploratory Outcome - Diabetes duration

Time: up to 12-weeks

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Description: Diabetes Self-Management and Technology Questionnaire (DSMT-Q); Minimum score: 0; maximum score: 48; higher score represented a worse outcome.

Measure: Exploratory Outcome - Diabetes self-management

Time: up to 12-weeks

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Primary Outcomes

Measure: Maximum plasma concentration [C(max)]

Time: Hour 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 16 on Day 1, Hour 24 and 36 on Day 2, Hour 48 on Day 3

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Measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC(inf)]

Time: Hour 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 16 on Day 1, Hour 24 and 36 on Day 2, Hour 48 on Day 3

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Measure: Area under the plasma concentration-time [AUC(last)]

Time: Hour 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 16 on Day 1, Hour 24 and 36 on Day 2, Hour 48 on Day 3

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Measure: Fraction of unbound drug in plasma [fu]

Time: Hour 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 16 on Day 1, Hour 24 and 36 on Day 2, Hour 48 on Day 3

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Secondary Outcomes

Measure: Unbound Maximum Observed Plasma Concentration [C(max,u)]

Time: Hour 0 and 4 on Day 1

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Measure: Unbound area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(inf,u)]

Time: Hour 0 and 4 on Day 1

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Measure: Unbound area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration [AUC[last,u])

Time: Hour 0 and 4 on Day 1

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Measure: Apparent Oral Clearance [CL/F]

Time: Hour 0 and 4 on Day 1

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Measure: Apparent clearance of unbound drug [CL(u)/F]

Time: Hour 0 and 4 on Day 1

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Measure: Apparent volume of distribution [V(z)/F]

Time: Hour 0 and 4 on Day 1

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Measure: Time to Reach Maximum Observed Plasma Concentration [T(max)]

Time: Hour 0 and 4 on Day 1

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Measure: Time measured for plasma concentration to decrease by one half (Terminal half-life) [t(1/2)].

Time: Hour 0 and 4 on Day 1

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Measure: Incidence and severity of treatment emergent adverse events (AEs and SAEs)

Time: Baseline through Day 28

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Measure: Incidence of treatment emergent clinical laboratory abnormalities

Time: Baseline to Day 3

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Measure: Incidence of treatment emergent vital signs

Time: Baseline, Day 1 and Day 3

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Measure: Incidence of treatment emergent Electrocardiogram [ECG] abnormalities

Time: Baseline, Day 1 and Day 3

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