Omaveloxolone is approved for the treatment of Friedreich ataxia (FA) in patients aged ≥ 16 years at a dose of 150 mg once daily. This double-blind, randomized, placebo- and active-controlled, three-way crossover, thorough corrected QT interval (QTc) study (NCT05927649) evaluated the effect of supratherapeutic omaveloxolone exposure on QTc to exclude a clinically significant prolongation (defined as >
10 ms). Healthy adults were randomized to one of six sequences of three single oral doses (omaveloxolone 450 mg, placebo, or moxifloxacin 400 mg [open-label positive control]) administered with an FDA high-fat meal. Serial pharmacokinetic blood sampling and time-matched electrocardiogram assessments were performed. The primary endpoint was placebo-corrected change from baseline in QTcF (ΔΔQTcF) following omaveloxolone administration. Secondary endpoints included pharmacokinetic parameters of omaveloxolone and its major plasma metabolites (M17 and M22) and safety. All 30 enrolled participants completed the study. The mean omaveloxolone C