Safety and Efficacy Study of A0001 in Subjects With Friedreich's Ataxia

Study Overview
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Brief Summary
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This is a Phase 2a double-blind, placebo-controlled study with two dose levels of A0001 given twice daily for 28 days. Potential subjects will be screened first to determine eligibility, after which they will be randomized to receive either a high dose of A0001, a low dose of A0001 or placebo for 28 days. Eligible subjects will return within 21 days of screening for the baseline visit and randomization to one of three potential treatments. The subjects will be required to take 3 capsules of study medication in the morning with a morning meal and 3 capsules of study medication at night with an evening meal for 28 days. Additional visits to the clinic are planned for Day 14 and Day 28, at which time a number of clinical and biochemical assessments will be done.

Official Title
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A Phase 2a, Double-Blind, Randomized, Placebo-Controlled, 28 Day, Three-arm, Parallel Group Study of A0001 in the Treatment of Subjects With Friedreich's Ataxia

Conditions
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Friedreich's Ataxia

Intervention / Treatment
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* Drug: alpha-tocopherolquinone (A0001)
* Drug: alpha-tocopherolquinone (A0001)
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals with genetically confirmed Friedreich's Ataxia (GAA or point mutation) Impaired Glucose Tolerance, measured by Oral GTT Exclusion Criteria: Overt Diabetes Mellitus Presence of clinically significant cardiovascular disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose<br>A0001 (0.5 g BID) | Drug: alpha-tocopherolquinone (A0001)<br>* 28 days of low dose (1.0 g total daily dose) oral A0001 capsules. Treatment taken twice daily with meals.<br>|
| Experimental: High Dose<br>A0001 (0.75 g BID) | Drug: alpha-tocopherolquinone (A0001)<br>* 28 days of high dose (1.5 g total daily dose) oral A0001 capsules. Treatment taken twice daily with meals.<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: placebo<br>* 28 days of placebo oral capsules. Treatment taken twice daily with meals.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Disposition Index of Glucose Regulation, determined by Frequent Sampling IV Glucose Tolerance Test |  | Baseline, Day 14 and Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity index (SI) calculated from IVGTT |  | Baseline, Day 14 and Day 28 | 
| Glucose effectiveness (SG) calculated from IVGTT |  | Baseline, Day 14 and Day 28 | 
| AIRg for glucose and insulin during IVGTT |  | Baseline, Day 14 and Day 28 | 
| Fasting Glucose, Insulin and Lactate |  | Baseline, Day 14 and Day 28 | 
| HbA1C |  | Baseline, Day 14 and Day 28 | 
| Plasma 1,5-anhydroglucitol (1,5-AG) (Glycomark) |  | Baseline, Day 14 and Day28 | 
| Specific Activity of Complex 1 in whole blood |  | Baseline, Day 14 and Day 28 | 
| Timed 25 Foot Walk Test |  | Baseline and Day 28 | 
| FARS/neurological exam |  | Baseline and Day 28 | 
| 9-Hole Peg Test |  | Baseline, Day 14 and Day 28 | 
| Vision Low Contrast Letter Acuity Test |  | Baseline and Day 28 | 
| Global Impression of Clinical Severity |  | Baseline, Day 14 and Day 28 | 
| Modified Fatigue Impact Scale |  | Baseline and Day 28 | 
| Activities of Daily Living |  | Baseline and Day 28 | 
| SF-36® |  | Baseline and Day 28 |