Clinical trial NCT01074359: Safety and Efficacy Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Neuromuscular Disease
Keywords: A3243G Mitochondrial DNA Point Mutation
Lead sponsor: Penwest Pharmaceuticals Co.
Sponsor class: INDUSTRY
First posted: 2010-02-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Improvement in the rate of ATP recovery ("Vmax") in cardiac muscle as measured by 31Phosphorous Magnetic Resonance Spectroscopy (31P-MRS)
timeFrame: Baseline and Day 28
Secondary outcomes:
measure: Improvement in cardiac structure and function as measured by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline and Day 28
measure: Exercise tolerance as measured by a 6 minute walk test
timeFrame: Baseline, Day 14 and Day 28
measure: Improvement in the rate of Maximal ATP recovery (Vmax) as measured by 31Phosphorous Magnetic Resonance Spectroscopy (31P-MRS) MRI of calf muscle during a standardized isolated calf muscle procedure of 2 bouts of plantar flexion exercise
timeFrame: Baseline and Day 28
measure: Fasting blood lactate, fasting blood glucose, fasting blood insulin , fasting blood HbA1c levels
timeFrame: Baseline, Day 14 and Day 28
measure: Mitochondrial disease severity (NMDAS)
timeFrame: Baseline and Day 28
measure: Quality of life (SF-36® Health Survey Questionnaire)
timeFrame: Baseline and Day 28
measure: Global impression of clinical severity
timeFrame: Baseline, Day 14 and Day 28
measure: Modified fatigue impact scale
timeFrame: Baseline, Day 14 and Day 28
Other outcomes:
Locations:
city: Newcastle
country: United Kingdom
facility: University of Newcastle upon Tyne
state: Framlington Place
Study officials:
affiliation: University of Newcastle Upon-Tyne
name: Patrick F Chinnery
role: PRINCIPAL_INVESTIGATOR
References: