Clinical trial NCT01035671: Safety and Efficacy Study of A0001 in Subjects With Friedreich's Ataxia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Friedreich's Ataxia
Lead sponsor: Penwest Pharmaceuticals Co.
Sponsor class: INDUSTRY
First posted: 2009-12-21
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Disposition Index of Glucose Regulation, determined by Frequent Sampling IV Glucose Tolerance Test
timeFrame: Baseline, Day 14 and Day 28
Secondary outcomes:
measure: Sensitivity index (SI) calculated from IVGTT
timeFrame: Baseline, Day 14 and Day 28
measure: Glucose effectiveness (SG) calculated from IVGTT
timeFrame: Baseline, Day 14 and Day 28
measure: AIRg for glucose and insulin during IVGTT
timeFrame: Baseline, Day 14 and Day 28
measure: Fasting Glucose, Insulin and Lactate
timeFrame: Baseline, Day 14 and Day 28
measure: HbA1C
timeFrame: Baseline, Day 14 and Day 28
measure: Plasma 1,5-anhydroglucitol (1,5-AG) (Glycomark)
timeFrame: Baseline, Day 14 and Day28
measure: Specific Activity of Complex 1 in whole blood
timeFrame: Baseline, Day 14 and Day 28
measure: Timed 25 Foot Walk Test
timeFrame: Baseline and Day 28
measure: FARS/neurological exam
timeFrame: Baseline and Day 28
measure: 9-Hole Peg Test
timeFrame: Baseline, Day 14 and Day 28
measure: Vision Low Contrast Letter Acuity Test
timeFrame: Baseline and Day 28
measure: Global Impression of Clinical Severity
timeFrame: Baseline, Day 14 and Day 28
measure: Modified Fatigue Impact Scale
timeFrame: Baseline and Day 28
measure: Activities of Daily Living
timeFrame: Baseline and Day 28
measure: SF-36®
timeFrame: Baseline and Day 28
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: David Lynch, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lynch DR, Willi SM, Wilson RB, Cotticelli MG, Brigatti KW, Deutsch EC, Kucheruk O, Shrader W, Rioux P, Miller G, Hawi A, Sciascia T. A0001 in Friedreich ataxia: biochemical characterization and effects in a clinical trial. Mov Disord. 2012 Jul;27(8):1026-33. doi: 10.1002/mds.25058. Epub 2012 Jun 28.
citation: Friedman LS, Schadt KA, Regner SR, Mark GE, Lin KY, Sciascia T, St John Sutton M, Willi S, Lynch DR. Elevation of serum cardiac troponin I in a cross-sectional cohort of asymptomatic subjects with Friedreich ataxia. Int J Cardiol. 2013 Aug 20;167(4):1622-4. doi: 10.1016/j.ijcard.2012.04.159. Epub 2012 May 26.