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

Neuromuscular Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01074359
• Other study ID #: MEL01
• Status: Terminated
• Phase: Phase 2
• First received: February 22, 2010
• Last updated: April 21, 2011
• Start date: February 2010
• Est. completion date: November 2010

Study information

• Verified date: April 2011
• Source: Penwest Pharmaceuticals Co.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuromuscular Disease
• Neuromuscular Diseases

Intervention

Drug:
• A0001 (alpha-tocopherolquinone)
28 days (1.5 g total daily dose) oral A0001 capsules. Treatment taken twice daily with meals.
• Placebo
28 days of placebo oral capsules. Treatment taken twice daily with meals.

Locations

Country	Name	City	State
United Kingdom	University of Newcastle upon Tyne	Newcastle	Framlington Place

Sponsors (1)

Lead Sponsor	Collaborator
Penwest Pharmaceuticals Co.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in the rate of ATP recovery ("Vmax") in cardiac muscle as measured by 31Phosphorous Magnetic Resonance Spectroscopy (31P-MRS)		Baseline and Day 28	No
Secondary	Improvement in cardiac structure and function as measured by Magnetic Resonance Imaging (MRI)		Baseline and Day 28	No
Secondary	Exercise tolerance as measured by a 6 minute walk test		Baseline, Day 14 and Day 28	No
Secondary	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	No
Secondary	Fasting blood lactate, fasting blood glucose, fasting blood insulin , fasting blood HbA1c levels		Baseline, Day 14 and Day 28	No
Secondary	Mitochondrial disease severity (NMDAS)		Baseline and Day 28	No
Secondary	Quality of life (SF-36® Health Survey Questionnaire)		Baseline and Day 28	No
Secondary	Global impression of clinical severity		Baseline, Day 14 and Day 28	No
Secondary	Modified fatigue impact scale		Baseline, Day 14 and Day 28	No