Friedreich's ataxia (FRDA) is a progressive, autosomal recessive, multisystem degenerative disease for which there is currently no effective treatment. Recent studies suggest that lipid-soluble antioxidants may prevent the progression of neurodegeneration and lead to some reversal of cardiomyopathy.

This will be a phase Ia, unblinded, dose-escalation trial examining the toxicity and tolerability of the antioxidant idebenone in patients with FRDA. Our primary objective is to determine the maximum tolerated single dose of idebenone in patients with FRDA. Our secondary objective is to document the pharmacokinetics of single-dose idebenone in this population. We aim to enroll 48 patients divided evenly among three age cohorts: children (ages 5-11), adolescents (ages 12-17), and adults (age greater than or equal to 18). Each age cohort will be studied independently. Three patients from each cohort will receive one day of oral idebenone followed by inpatient monitoring for 72 hours. If dose-limiting toxicity (DLT) is not observed during the 72-hour study period, three new patients will receive the next highest dose. If one of three patients experiences DLT, three new patients will receive the same dose. Within each cohort, the dose will be escalated until the maximum tolerated dose (MTD) is established. The MTD will be defined as one dose below that which resulted in DLT in any two patients within a cohort.

Subsequent to the completion of this phase Ia trial, we plan to further refine the MTD for each age group in a phase Ib trial in which we will examine multiple-dose regimens over a longer study period. We hope to follow these phase I studies with a double-blinded, placebo-controlled phase II trial to further evaluate safety and to estimate the efficacy of idebenone using cardiac parameters as our primary endpoints. In addition, we are currently in the process of validating a clinical evaluation scale for FRDA that we hope to employ in measuring neurological parameters as a secondary endpoint in the phase II trial.