Primary Outcomes

Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments. The RTI task of CANTAB involves elements of decision-making and attention as measured by choice accuracy as well as motor responses, by measuring motor and mental response speeds, and assesses movement time, reaction time, response accuracy, and impulsivity. This outcome measure will be assessed at Week 10 in both Part A and Part B of the study.

Measure: Change from Baseline in the Reaction Time (RTI) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Week 10

Time: Baseline, Week 10

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Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments. The RTI task of CANTAB involves elements of decision-making and attention as measured by choice accuracy as well as motor responses, by measuring motor and mental response speeds, and assesses movement time, reaction time, response accuracy, and impulsivity. This outcome measure will be assessed at Week 18 in Part A of the study.

Measure: Change from Baseline in the Reaction Time (RTI) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Week 18

Time: Baseline, Week 18

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Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments. The RTI task of CANTAB involves elements of decision-making and attention as measured by choice accuracy as well as motor responses, by measuring motor and mental response speeds, and assesses movement time, reaction time, response accuracy, and impulsivity. This outcome measure will be assessed at Week 49 in both Part A and Part B of the study.

Measure: Change from Baseline in the Reaction Time (RTI) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Week 49

Time: Baseline, Week 49

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Secondary Outcomes

Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments. Cognitive domain, sustained attention will be measured by the CANTAB RVP task. RVP measures the ability to sustain attention over time and is a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo--random order at a rate of 100 digits per minute in a box at the center of the screen. Participants are to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen.

Measure: Change from Baseline in the Rapid Visual Information Processing (RVP) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) in Both Part A and Part B at Specified Time Points

Time: Part A: Baseline, Week 10, Week 18, Week 49 Part B: Baseline, Week 10, Week 49

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Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments, SWM is a component of cognitive executive function which is measured by SWM task of CANTAB between the errors. The ability to retain spatial information and manipulate remembered items in working memory will be measured with the SWM task of CANTAB which is self-ordered and assesses the individual's ability to strategize heuristically. The test is a sensitive measure of frontal lobe and executive dysfunction.

Measure: Change from Baseline in the Spatial Working Memory (SWM) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) in Both Part A and Part B at Specified Time Points

Time: Part A: Baseline, Week 10, Week 18, Week 49 Part B: Baseline, Week 10, Week 49

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Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments.Response control or inhibition cognitive domain will be measured by the CANTAB SST. SST measure response inhibition. The participant must respond to an arrow stimulus by touching either of 2 choices depending on the direction the arrow points. If an audio tone is present, the participant is not to respond.

Measure: Change from Baseline in the Stop Signal Task (SST) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) in Both Part A and Part B at Specified Time Points

Time: Part A: Baseline, Week 10, Week 18, Week 49 Part B: Baseline, Week 10, Week 49

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Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments. Recognition memory of cognition domain will be measured by the CANTAB DMS task. DMS measures both simultaneous matching and short-term visual memory. The participant is shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample.

Measure: Change from Baseline in the Delayed Matching to Sample (DMS) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) in Both Part A and Part B at Specified Time Points

Time: Part A: Baseline, Week 10, Week 18, Week 49 Part B: Baseline, Week 10, Week 49

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Description: Sexual maturation will be measured by Tanner stage. The stage of puberty or sexual maturation will be evaluated for each participant according to Tanner staging. The Tanner stage for genitals (male, stages I-V), breasts (females, stages I-V), and pubic hair (both sexes, stages I-V) will be documented at the specified times.

Measure: Tanner Stage in Both Part A and Part B at Specified Time Points

Time: Part A: Baseline, Week 10, Week 18, Week 49 Part B: Baseline, Week 10, Week 49

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Description: Physical examinations will include height and weight. Growth will be measured by weight, height, and BMI. Body mass index is a measure of body fat based on height and weight. Vital signs will be assessed based on blood pressure, pulse rate, respiratory rate and body temperature in both Part A and Part B. The HR, PR interval, QRS interval, and QT interval will be measured from all ECGs and the QTcB and QTcF assessed at specified time points in both Part A and Part B of the study.

Measure: Number of participants with clinically significant changes in Vital signs, ECG, Physical Examination

Time: From start of study drug administration up to follow up (week 52)

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Description: Psychiatric symptoms will be measured by the Brief Psychiatric Rating Scale for Children (BPRS-C) total score. The 21 items of the clinician-rated BPRS-C are grouped into the following 7 scales: depression, anxiety, psychomotor excitation, behavior problems, withdrawal retardation, thinking disturbance, and organicity. Each item of the 21 items is clinician-graded using the following 7-point severity Likert-scale from 0 to 6 (not present=0; very mild=1; mild=2; moderate=3; moderately severe=4; severe=5; extremely severe=6. BPRS-C will be assessed at specified time points in both Part A and Part B.

Measure: Brief Psychiatric Rating Scale for Children (BPRS-C)

Time: Part A: Baseline, Week 10, Week 18, Week 23, Week 36 and Week 49 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49

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Description: The C-SSRS is a structured tool to assess suicidal ideation and behavior. A maximum of 19 items will be completed as follows: 7 items are required, a potential 10 additional items will be completed upon a positive response to a required item, and 2 items completed if suicide or suicide-like behavior is observed during the interview. The C-SSRS uses dichotomous scales (i e, yes or no), Likert scales, and text or narrative to further describe thoughts or behaviors. C-SSRS Score will be assessed at specified time points in both Part A and Part B.

Measure: Columbia- Suicide Severity Rating Scale (CSSRS)

Time: Baseline (from start of study drug administration) to Week 52

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Description: UKU rating scale was developed for clinicians to assess side effects of psychopharmacological medications based on interviews and other relevant source information. UKU items relevant to the established safety profile of SPD503 such as Increased Duration of Sleep, Asthenia or Lassitude or lncreased Fatigability, Sleepiness or Sedation, and Orthostatic Dizziness. UKU rating scale will be assessed at specified time points in both Part A and Part B.

Measure: Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale

Time: Part A: Baseline, Week 10, Week 18, Week 23, Week 36, Week 49, Week 50, Week 51 and Week 52 Part B: Baseline, Week 10, Week 23, Week 36, Week 49, Week 50, Week 51 and Week 52

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Description: Sedative effects will be measured by participant ratings on the Pediatric Daytime Sleepiness Scale (PDSS). The PDSS is a self-reported assessment of daytime sleepiness in children aged 11 to 15 years. PDSS questionnaire was designed to be easy to administer, score, and interpret. Sleepiness-related questions are based on previous research of situations that can be sensitive to sleep loss in this age group. The 8 questions are scored on Likert-scale from 0 to 4 (never=0; seldom=1; sometimes=2; frequently=3; always=4). The total score on the PDSS can range from 0 (never sleepy) to 32 (always sleepy). PDSS will be assessed at specified time points in both Part A and Part B.

Measure: Pediatric Daytime Sleepiness Scale (PDSS)

Time: Part A: Baseline, Week 10, Week 18, Week 23, Week 36 and Week 49 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49

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Description: The ADHD-RS-5 (DuPaul et al., 2016) is used widely by mental health, educational, and medical practitioners in screening, diagnosis, and treatment evaluation to determine the frequency and severity of ADHD symptoms and impairments in children and adolescents. Attention-deficit/hyperactivity disorder symptoms is measured by the investigator-administered ADHD Rating Scale-5 (ADHD-RS-5) total score and hyperactivity/impulsivity and inattentiveness symptoms as subscale scores. The ADHD-RS-5 is based on the diagnostic criteria for ADHD as described in the DSM-5 and consists of 2 symptom subscales, inattention and hyperactivity-impulsivity, each with 9 items and a total scale of 18 items. Each item in the subscale is scored with a value ranging from 0 (no symptoms) to 3 (severe symptoms). The total score can range from 0 to 54. ADHD-RS-5 Total Score and Subscales wiil be assessed at specified time points in both Part A and Part B.

Measure: ADHD Rating Scale-5 (ADHD-RS-5) Total Score and Subscales

Time: Part A: Baseline, Week 1, Week 10, Week 18, Week 23, Week 36 and Week 49 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49

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Description: Global clinical measurement of ADHD improvement as measured by Clinical Global Impression-Improvement (CGI-I) using the Clinical Global Impression-Severity (CGI-S) to establish baseline. The CGI scale will be used to evaluate the severity of mental illness over time. The CGI-S will be administered to assess the severity of mental illness at baseline. The CGI-S is scored on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The CGI-I is also scored on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). CGI-I will be measured at specified time points in both Part A and Part B.

Measure: Clinical Global Impression-Improvement (CGI-I)

Time: Part A: Week 1, Week 10, Week 18, Week 23, Week 36 and Week 49 Part B: Week 10, Week 23, Week 36 and Week 49

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Description: The Parent Report Form of the Child Health and Illness Profile - Child Edition (CHIP-CE:PRF) will be administered to provide information on self-esteem and school functioning in pediatric participants diagnosed with ADHD. The 5 domains and 12 subdomains covered in the 76 items comprising the CHIP-CE:PRF. Satisfaction: with health (7 items) and self (4 items); Comfort: physical (9 items) and emotional symptoms (9 items) and activity restrictions (4 items) due to illness; Resilience: behaviors and family involvement (8 items) in activities likely to enhance health, Social problem-solving (5 items),Physical activity (6 items); Risk avoidance: behaviors that if not avoided are likely to pose risks to health: Individual risk avoidance (4 items), Threats to achievement (10 items); Achievement: developmentally appropriate role functioning in school and with peers: Academic performance (5 items), Peer relations (5 items). CHIP-CE: PRF will be assessed in both Part A and Part B.

Measure: Child Health and Illness Profile - Child Edition: Parent Report Form (CHIP-CE:PRF)

Time: Part A: Baseline, Week 10, Week 18, Week 23, Week 36 and Week 49 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49

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Description: School performance will be measured by teacher ratings of academic skills using the APRS at specified time points in both Part A and Part B. The APRS is a reliable rating scale that has been shown to be valid in assessing teacher perceptions of the quality of a student's academic competency. The scale includes 19 items that are directed toward work performance in various participant areas; academic success, behavioral control in academic situations, and attention to assignments. Teachers mark responses in a Likert-scale format from 1 (never or poor) to 5 (very often or excellent). From the APRS, a total score and the following 3 subscale scores are calculated: academic success, impulse control, and academic productivity.

Measure: Academic Performance Rating Scale (APRS)

Time: Part A: Baseline, Week 10, Week 18, Week 23, Week 36 and Week 49 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49

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Primary Outcomes

Measure: Clearance (CL) or apparent oral clearance (CL/F) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: Volume of distribution (V) or apparent oral volume of distribution (V/F) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: Elimination rate constant (ke) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: Half-life (t1/2) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: Absorption rate constant (ka) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: AUC (area under the curve) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: Maximum concentration (Cmax) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: Time to achieve maximum concentration (Tmax) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Primary Outcomes

Description: composition, home confinement, change in the environment, personal room at home, screens with internet access, parents' current professional status, teleworking, care, family concerns related to Covid-19, parenting stress, schooling, recurrent complaints.

Measure: Interview of the parents : contextual data

Time: Baseline

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Description: related to education; related to daily family life; related to leisure, related to care (children/adolescents, parents)

Measure: Interview of the children/adolescents/ parents : Experience of the confinement in general

Time: Baseline

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Description: related to education; related to daily family life; related to leisure, related to care (children/adolescents, parents)

Measure: Interview of the children/adolescents/ parents : Experience of the confinement in general

Time: 1 month

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Description: related to education; related to daily family life; related to leisure, related to care (children/adolescents, parents)

Measure: Interview of the children/adolescents/ parents : Experience of the confinement in general

Time: 3 months

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Description: Data relating to disease and management of care. Experience of the referring caregiver.

Measure: Interview of the referring caregiver : data relating to disease and management of care

Time: 3 months

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Primary Outcomes

Measure: Neurodevelopmental Outcomes

Time: 3-4 years of age

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