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

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

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.

Study Overview

• Status: Terminated
• Conditions: Neuromuscular Disease
• Intervention / Treatment: Drug: A0001 (alpha-tocopherolquinone); Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Framlington Place
    • Newcastle, Framlington Place, United Kingdom, NE2 4HH
      • University of Newcastle upon Tyne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 28 days of placebo oral capsules. Treatment taken twice daily with meals.
Experimental: A0001; A0001 (0.75 g BID)	Drug: A0001 (alpha-tocopherolquinone); 28 days (1.5 g total daily dose) oral A0001 capsules. Treatment taken twice daily with meals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Quality of life (SF-36® Health Survey Questionnaire)	Baseline and Day 28
Global impression of clinical severity	Baseline, Day 14 and Day 28
Modified fatigue impact scale	Baseline, Day 14 and Day 28

Collaborators and Investigators

• Sponsor: Penwest Pharmaceuticals Co.
• Investigators: Principal Investigator: Patrick F Chinnery, University of Newcastle Upon-Tyne

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: February 22, 2010
• First Submitted That Met QC Criteria: February 23, 2010
• First Posted (Estimate): February 24, 2010

Study Record Updates

• Last Update Posted (Estimate): April 22, 2011
• Last Update Submitted That Met QC Criteria: April 21, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: A3243G Mitochondrial DNA Point Mutation
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Protective Agents; Anticoagulants; Antioxidants; Tocopherylquinone
• Other Study ID Numbers: MEL01