This is a single-center, randomized, double-blind, placebo-controlled, sequential group study. The primary objective of this study is to assess the tolerability and safety of single doses of ME1100 inhalation solution (orally inhaled arbekacin). The secondary objective is to determine the systemic exposure to, and urinary elimination of, ME1100.

NCT01907776

Conditions

1. Healthy

Interventions

1. Drug: ME1100 inhalation solution
2. Drug: ME1100 placebo inhalation solution

heteroplasmy) suggestive of increased risk of hearing loss (MT-RNR1 [A1555G] for mitochondrial 12S ribosomal RNA gene or MT-TS1 [A3243G] for mitochondrial transfer RNA serine 1) - History of parent, sibling or parental sibling reporting hearing loss before age 65 years - History of malignancy - History of clinically significant alcohol or drug abuse - History within last 6 months or current use of any tobacco product including e-cigarettes - Positive drug screen for drugs of abuse - Positive test for HIV, Hepatitis B or Hepatitis C - Use of any prescription or over-the-counter medications (except oral or hormonal contraceptives), herbal supplements, or vitamins within 14 days of Visit 2 - Known hypersensitivity to any aminoglycoside or bacitracin antibiotic - Female of childbearing potential with a positive urine pregnancy test, or currently breast feeding. --- A1555G --- --- A3243G ---

This is a single-center, open-label, single-dose study. The primary objective is to determine Epithelial Lining Fluid (ELF) levels of ME1100 after a single orally inhaled dose. The secondary objectives are to determine systemic exposure to inhaled ME1100 and to assess tolerability and safety of a single dose of ME1100 inhalation solution.

NCT01961830

Conditions

1. Healthy

Interventions

1. Drug: ME1100 inhalation solution

heteroplasmy) suggestive of increased risk of hearing loss (MT-RNR1 [A1555G] for mitochondrial 12S ribosomal RNA gene or MT-TS1 [A3243G] for mitochondrial transfer RNA serine 1) - History of parent, sibling or parental sibling reporting hearing loss before age 65 years - History of malignancy - History of clinically significant alcohol or drug abuse - History within last 6 months or current use of any tobacco products including e-cigarettes. --- A1555G --- --- A3243G ---

Patients with the MELAS syndrome experience devastating mental impairment. This study will evaluate the effectiveness of the drug dichloroacetate (DCA) to reduce the symptoms of MELAS.

NCT00068913

Conditions

1. MELAS Syndrome

Interventions

1. Drug: Dichloroacetate

MeSH:MELAS Syndrome Syndrome

Inclusion Criteria - A3243G mtDNA point mutation or maternally related to someone who has the mutation - Symptomatic with MELAS, including previous seizure or stroke - Certain laboratory values - Ability to comply with the study protocol Inclusion Criteria - A3243G mtDNA point mutation or maternally related to someone who has the mutation - Symptomatic with MELAS, including previous seizure or stroke - Certain laboratory values - Ability to comply with the study protocol MELAS Syndrome MELAS Syndrome Syndrome Although many organ systems are affected by mitochondrial (mt) DNA point mutations, the nervous system is particularly vulnerable. --- A3243G ---

Inclusion Criteria - A3243G mtDNA point mutation or maternally related to someone who has the mutation - Symptomatic with MELAS, including previous seizure or stroke - Certain laboratory values - Ability to comply with the study protocol Inclusion Criteria - A3243G mtDNA point mutation or maternally related to someone who has the mutation - Symptomatic with MELAS, including previous seizure or stroke - Certain laboratory values - Ability to comply with the study protocol MELAS Syndrome MELAS Syndrome Syndrome Although many organ systems are affected by mitochondrial (mt) DNA point mutations, the nervous system is particularly vulnerable. --- A3243G --- --- A3243G ---

Patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome have the A3243G point mutation and elevated brain lactate levels. --- A3243G ---

Patients with the A3243G mitochondrial mutation and who have had either a stroke or a seizure will be enrolled in this study. --- A3243G ---

MELAS patients suffer from exercise intolerance, weakness, poor vision or blindness, poor growth, developmental delay, and deafness. They also have unique 'stroke-like' episodes (SLEs) which are not due to blockages of large or medium arteries. These 'strokes' are thought to be due to energy failure of very small brain blood vessels combined with energy failure in the mitochondria (cell battery) of the brain cells, especially in the back region of the brain in the vision centre. This leads to visual loss and paralysis. The overall goal of this study is to better understand the mechanism of these SLEs at the level of the brain cells and small blood vessels.

NCT01603446

Conditions

1. MELAS Syndrome

Interventions

1. Drug: L-Arginine

MeSH:MELAS Syndrome Syndrome

Inclusion Criteria: Experimental Siblings with MELAS (A3243G) syndrome - 17-23 years - Followed Neurometabolic Clinic at the Hospital for Sick Children will be studied. --- A3243G ---

This is a phase 2a, double-blind, placebo-controlled, single-center study. Twenty-one patients who qualify for the study will be randomly assigned to either active drug or placebo. The study will take place at Newcastle University. Patients will have a 66% chance of getting active drug. Patients will be required to take study treatment orally twice a day for 28 days. A baseline visit will occur within 21 days of screening visit. All patients will be followed for 1 week after completion of study or early withdrawal from the study.

NCT01074359

Conditions

1. Neuromuscular Disease

Interventions

1. Drug: A0001 (alpha-tocopherolquinone)
2. Drug: Placebo

MeSH:Neuromuscular Diseases

A Phase 2a, Double Blind, Randomized, Placebo-controlled, 28 Day, Two-arm, Parallel Group Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation and Evidence of Impaired Mitochondrial Function. --- A3243G ---

Safety and Efficacy Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation This is a phase 2a, double-blind, placebo-controlled, single-center study. --- A3243G ---

Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Neuromuscular Disease Neuromuscular Diseases null --- A3243G ---

Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Neuromuscular Disease Neuromuscular Diseases null --- A3243G --- --- A3243G ---

Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Neuromuscular Disease Neuromuscular Diseases null --- A3243G --- --- A3243G --- --- A3243G ---

Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Neuromuscular Disease Neuromuscular Diseases null --- A3243G --- --- A3243G --- --- A3243G --- --- A3243G ---

The purpose of this study is to compare the efficacy of two (2) different doses of idebenone with that of a placebo over a one month period on cerebral lactate concentration as measured by magnetic resonance spectroscopy.

NCT00887562

Conditions

1. MELAS Syndrome

Interventions

1. Drug: Idebenone
2. Drug: Idebenone
3. Other: Placebo

MeSH:MELAS Syndrome Brain Diseases Acidosis Acidosis, Lactic

HPO:Acidosis Encephalopathy Lactic acidosis Metabolic acidosis

Inclusion Criteria: - Diagnosis of MELAS with confirmed A3243G mtDNA mutation, or evidence of central nervous system involvement (cognitive problems, migraines, memory loss) - Cerebral lactate level equal to or greater than 5.0 i.u. at baseline - Patients at least 8 and < 65 years of age at baseline - Patients with a body weight > 37 kg/82 lbs at baseline - Stable co-medication/vitamins/supplements within 1 month prior to baseline - Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the study medication - Negative urine pregnancy test at screening and baseline (female patients of childbearing potential) Exclusion Criteria: - Contraindication to MRS (e.g. --- A3243G ---

metal implant, claustrophobia) - Stroke like event within 2 months prior to baseline - Treatment with idebenone at any dose, or coenzyme Q10 at doses above 100mg/d within 1 month prior to baseline - Inadequate contraception use - Pregnancy and/or breast-feeding - Clinically significant abnormalities of clinical hematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or creatinine - Current abuse of drugs or alcohol - Participation in a trial of another investigational drug within the last month - Other factor that, in the investigator's opinion, excludes the patient from entering the study Inclusion Criteria: - Diagnosis of MELAS with confirmed A3243G mtDNA mutation, or evidence of central nervous system involvement (cognitive problems, migraines, memory loss) - Cerebral lactate level equal to or greater than 5.0 i.u. at baseline - Patients at least 8 and < 65 years of age at baseline - Patients with a body weight > 37 kg/82 lbs at baseline - Stable co-medication/vitamins/supplements within 1 month prior to baseline - Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the study medication - Negative urine pregnancy test at screening and baseline (female patients of childbearing potential) Exclusion Criteria: - Contraindication to MRS (e.g. --- A3243G ---

Given that there is no effective treatment for MELAS, the investigators propose a Phase II proof of concept trial of idebenone to study its preliminary efficacy in patients with MELAS and the A3243G mtDNA mutation, and to study its safety and tolerability in this patient group. --- A3243G ---

The investigators propose to evaluate 21 patients with the A3243G mitochondrial DNA mutation and MELAS (defined by a history of either seizures or stroke). --- A3243G ---