A Randomized, Double-Blind, Placebo- and Positive-Controlled, 4-Period Crossover Study of the Effects of Solriamfetol on QTcF Intervals in Healthy Participants.

ABSTRACT

Solriamfetol, a dopamine and norepinephrine reuptake inhibitor, is approved (United States and European Union; Sunosi) to treat excessive daytime sleepiness associated with narcolepsy (75-150 mg/day) or obstructive sleep apnea (37.5-150 mg/day). A thorough QT/QTc study assessed solriamfetol effects on QT interval (Fridericia correction for heart rate; QTcF). This randomized, double-blind, placebo- and positive-controlled, 4-period crossover study compared single doses of 300 and 900 mg solriamfetol, 400 mg moxifloxacin, and placebo in healthy adults. Placebo- and predose-adjusted mean differences in QTcF (ddQTcF; primary end point) were analyzed, and solriamfetol pharmacokinetics were characterized. Fifty-five participants completed all periods. Upper bounds of 2-sided 90% confidence intervals (CIs) for ddQTcF for both solriamfetol doses were <10 milliseconds at all postdose time points. Assay sensitivity was demonstrated with moxifloxacin; lower bounds of 2-sided 90%CIs for ddQTcF > 5 milliseconds at 1, 2, and 3 hours postdose. There were no QTcF increases > 60 milliseconds or QTcF values > 480 milliseconds at either solriamfetol dose. Solriamfetol median tmax was 2-3 hours; exposure was dose-proportional. More participants experienced adverse events (AEs) after solriamfetol 900 versus 300 mg (70% vs 29%); none were serious (all mild/moderate), and there were no deaths. Common AEs were nausea, dizziness, and palpitations. Neither solriamfetol dose resulted in QTcF prolongation > 10 milliseconds.