Safety and Efficacy Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation - Full Text View

Sponsor:	Penwest Pharmaceuticals Co.
Information provided by:	Penwest Pharmaceuticals Co.
ClinicalTrials.gov Identifier:	NCT01074359

Purpose

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.

Condition	Intervention	Phase
Neuromuscular Disease	Drug: A0001 (alpha-tocopherolquinone) Drug: Placebo	Phase II

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

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Neuromuscular Disorders

U.S. FDA Resources

Further study details as provided by Penwest Pharmaceuticals Co.:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Improvement in cardiac structure and function as measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline and Day 28 ] [ Designated as safety issue: No ]
Exercise tolerance as measured by a 6 minute walk test [ Time Frame: Baseline, Day 14 and Day 28 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Fasting blood lactate, fasting blood glucose, fasting blood insulin , fasting blood HbA1c levels [ Time Frame: Baseline, Day 14 and Day 28 ] [ Designated as safety issue: No ]
Mitochondrial disease severity (NMDAS) [ Time Frame: Baseline and Day 28 ] [ Designated as safety issue: No ]
Quality of life (SF-36® Health Survey Questionnaire) [ Time Frame: Baseline and Day 28 ] [ Designated as safety issue: No ]
Global impression of clinical severity [ Time Frame: Baseline, Day 14 and Day 28 ] [ Designated as safety issue: No ]
Modified fatigue impact scale [ Time Frame: Baseline, Day 14 and Day 28 ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	February 2010
Study Completion Date:	November 2010
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.
Placebo Comparator: Placebo Placebo	Drug: Placebo 28 days of placebo oral capsules. Treatment taken twice daily with meals.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01074359

Locations

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

Sponsors and Collaborators

Penwest Pharmaceuticals Co.

Investigators

Principal Investigator:

Patrick F Chinnery

University of Newcastle Upon-Tyne

More Information

No publications provided

Responsible Party:	Thomas Sciascia, MD/Chief Medical Officer and VP Clinical Operations and Regulatory Affairs, Penwest Pharmaceuticals Co.
ClinicalTrials.gov Identifier:	NCT01074359 History of Changes
Other Study ID Numbers:	MEL01
Study First Received:	February 22, 2010
Last Updated:	April 21, 2011
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Penwest Pharmaceuticals Co.:

A3243G Mitochondrial DNA Point Mutation

Additional relevant MeSH terms:

Neuromuscular Diseases
Nervous System Diseases
Tocopherylquinone
Vitamin E
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents

Cardiovascular Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on February 08, 2012