Safety and Efficacy Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation

NCT01074359 | Terminated Phase 2

• 1 other identifier: MEL01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuromuscular Disease

Keywords

A3243G Mitochondrial DNA Point Mutation

Outcome Measures

Primary Outcomes (1)

• Improvement in the rate of ATP recovery ("Vmax") in cardiac muscle as measured by 31Phosphorous Magnetic Resonance Spectroscopy (31P-MRS)

  Baseline and Day 28

Secondary Outcomes (8)

• Improvement in cardiac structure and function as measured by Magnetic Resonance Imaging (MRI)

  Baseline and Day 28

• Exercise tolerance as measured by a 6 minute walk test

  Baseline, Day 14 and Day 28

• 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

  Baseline and Day 28

• Fasting blood lactate, fasting blood glucose, fasting blood insulin , fasting blood HbA1c levels

  Baseline, Day 14 and Day 28

• Mitochondrial disease severity (NMDAS)

  Baseline and Day 28

Study Arms (2)

A0001

EXPERIMENTAL

A0001 (0.75 g BID)

Drug: A0001 (alpha-tocopherolquinone)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

A0001 (alpha-tocopherolquinone) DRUG

28 days (1.5 g total daily dose) oral A0001 capsules. Treatment taken twice daily with meals.

A0001

Placebo DRUG

28 days of placebo oral capsules. Treatment taken twice daily with meals.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation
• PCR/ATP ratio of \<1.9 following the Cardiac MRS at screening

You may not qualify if:

• 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

Sponsors & Collaborators

• Penwest Pharmaceuticals Co.: lead

Study Sites (1)

University of Newcastle upon Tyne

Newcastle, Framlington Place, NE2 4HH, United Kingdom

Location

MeSH Terms

Conditions

Neuromuscular Diseases

Interventions

tocopherylquinone

Condition Hierarchy (Ancestors)

Nervous System Diseases

Study Officials

• Patrick F Chinnery

  University of Newcastle Upon-Tyne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 22, 2010
• First Posted: February 24, 2010
• Study Start: February 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: April 22, 2011

Record last verified: 2011-04

Locations

GB (1)