search
Back to results

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

Primary Purpose

Neuromuscular Disease

Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
A0001 (alpha-tocopherolquinone)
Placebo
Sponsored by
Penwest Pharmaceuticals Co.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuromuscular Disease focused on measuring A3243G Mitochondrial DNA Point Mutation

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Newcastle upon Tyne

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

A0001

Placebo

Arm Description

A0001 (0.75 g BID)

Placebo

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Improvement in cardiac structure and function as measured by Magnetic Resonance Imaging (MRI)
Exercise tolerance as measured by a 6 minute walk test
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
Fasting blood lactate, fasting blood glucose, fasting blood insulin , fasting blood HbA1c levels
Mitochondrial disease severity (NMDAS)
Quality of life (SF-36® Health Survey Questionnaire)
Global impression of clinical severity
Modified fatigue impact scale

Full Information

First Posted
February 22, 2010
Last Updated
April 21, 2011
Sponsor
Penwest Pharmaceuticals Co.
search

1. Study Identification

Unique Protocol Identification Number
NCT01074359
Brief Title
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

2. Study Status

Record Verification Date
April 2011
Overall Recruitment Status
Terminated
Why Stopped
Terminated for Commercial Reasons. There were no safety issues involved in the decision to terminate the study.
Study Start Date
February 2010 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Penwest Pharmaceuticals Co.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuromuscular Disease
Keywords
A3243G Mitochondrial DNA Point Mutation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A0001
Arm Type
Experimental
Arm Description
A0001 (0.75 g BID)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
A0001 (alpha-tocopherolquinone)
Intervention Description
28 days (1.5 g total daily dose) oral A0001 capsules. Treatment taken twice daily with meals.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
28 days of placebo oral capsules. Treatment taken twice daily with meals.
Primary Outcome Measure Information:
Title
Improvement in the rate of ATP recovery ("Vmax") in cardiac muscle as measured by 31Phosphorous Magnetic Resonance Spectroscopy (31P-MRS)
Time Frame
Baseline and Day 28
Secondary Outcome Measure Information:
Title
Improvement in cardiac structure and function as measured by Magnetic Resonance Imaging (MRI)
Time Frame
Baseline and Day 28
Title
Exercise tolerance as measured by a 6 minute walk test
Time Frame
Baseline, Day 14 and Day 28
Title
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
Time Frame
Baseline and Day 28
Title
Fasting blood lactate, fasting blood glucose, fasting blood insulin , fasting blood HbA1c levels
Time Frame
Baseline, Day 14 and Day 28
Title
Mitochondrial disease severity (NMDAS)
Time Frame
Baseline and Day 28
Title
Quality of life (SF-36® Health Survey Questionnaire)
Time Frame
Baseline and Day 28
Title
Global impression of clinical severity
Time Frame
Baseline, Day 14 and Day 28
Title
Modified fatigue impact scale
Time Frame
Baseline, Day 14 and Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick F Chinnery
Organizational Affiliation
University of Newcastle Upon-Tyne
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Newcastle upon Tyne
City
Newcastle
State/Province
Framlington Place
ZIP/Postal Code
NE2 4HH
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs