A3243G mitochondrial DNA point mutation and evidence of impaired mitochondrial function
Conditions
Interventions
Product Name: alpha-tocopherolquinone
Product Code: A0001
Pharmaceutical Form: Capsule, hard
Current Sponsor code: A0001
Other descriptive name: alpha-tocopherolquinone
Concentration unit: mg milligra
Sponsors
Penwest Pharmaceuticals Co.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient has been diagnosed as having neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation. 2. Male or female patients of any race within the age range of 18 to 70 years. 3. Sexually active participants and their partners must agree to use two forms of highly effective method of contraception or sterilisation from the time specified prior to screening through 30 days following the last dose of study drug: - Intra-uterine device (IUD) in place for at least 2 months prior to screening; - Barrier method (condom or diaphragm) with spermicide for at least 14 days prior to screening; - Stable hormonal contraceptive for at least 3 months prior to screening; - Sexually active male patients, including sterilized men, must use a condom for the duration of the trial. 4. Patient must have =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. 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. 2. Use of any investigational product within the past 30 days. 3. Patients with Dementia as defined by Mini Mental State Exam (MMSE) 2.0 x ULN), or prior evidence of a coagulation disorder. 5. History of or current gastro-intestinal diseases influencing drug absorption. 6. Patient is pregnant or lactating. 7. History, within 3 years, of drug abuse (including Benzodiazepines, opioids, amphetamine, cocaine, and THC). 8. History of alcoholism (within two years). 9. Patients taking warfarin or other anticoagulants. 10. Any currently known or expected increased risk of bleeding. 11. Uncontrolled diabetes. 12. Diagnosis of a coagulation disorder or a clinically significant abnormality in INR (>1.25x ULN). 13. Any subject considering or having scheduled any surgical procedure during the study or within a month after administration of the last dose of study. 14. Use of any new prescription drug therapy, or change in dose of existing therapy, within two weeks prior to receiving the first dose of study medication. 15. Known hypersensitivity or allergy to A0001, vitamin E, beta-carotene, or vehicle components or known allergies to drugs of the similar class which, in the opinion of the Investigator, suggests an increased potential for an adverse hypersensitivity to A0001. 16. Any patient judged by the Investigator or Sponsor (or designee) to be inappropriate for the study. 17. Presence of ACC/AHA Stage D cardiac failure at Screening defined as refractory heart failure requiring specialized interventions 18. Abnormal Troponin I level at Screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish proof-of-concept of the efficacy of A0001 in the treatment of patients with an established mitochondrial disorder using metabolic imaging, a number of functional assessments, biochemical measures and patient/clinician-rated scales.;Secondary Objective: To evaluate the tolerability and safety of A0001 in this patient population. To establish pharmacokinetics of A0001 in this patient population.;Primary end point(s): Improvement in the rate of ATP recovery (“Vmax”) in cardiac muscle as measured by 31-Phosphorous Magnetic Resonance Spectroscopy (31P-MRS) is the primary measure under investigation. Cardiac function will be assessed by several measures. The primary endpoint is the change in rate of ATP recovery (Vmax) and will be calculated as Day 28 - Baseline such that a positive value for the difference represents an improvement for the patient, i.e., a higher rate is desirable. The difference from baseline for A0001 will be compared against the change from baseline in the placebo group. The same analysis approach proposed for the change in rate of ATP recovery will be used for the analysis of the cardiac function on MRI. Although formally listed as a secondary endpoint, changes in LV volume and LV mass will be calculated as Day 28 - Baseline values such that a positive value for the difference represents an improvement for the patient, i.e., increased cardiac function. If a patient discontinues the study prior to obtaining the Day 28 observation, a last observation carried forward approach (LOCF) will be used to impute a Day 28 value for the change from baseline calculation. Assuming a normal distribution for the change from baseline data, an analysis of covariance (ANCOVA) will be used to evaluate the the overall effect of treatment, using the baseline disposition index as the covariate. If the distribution represents a severe departure from normality, a non-parametric approach using ranks will be considered. | — |
Countries
United Kingdom
Outcome results
None listed