A Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Interactions Between Alcohol and Sunobinop in Healthy Participants

BACKGROUND: Sunobinop is a potent, selective partial agonist at nociception/orphanin-FQ receptors with therapeutic potential in a variety of clinical disorders. This study assessed safety, tolerability, pharmacodynamics, and pharmacokinetic interactions of sunobinop and alcohol in healthy adults. METHODS: This was a single-center, randomized, blinded, crossover study in 48 participants. Single doses of placebo, sunobinop 2 mg (therapeutic), and 6 mg (supratherapeutic), were administered in the morning with alcohol or placebo. Pharmacokinetic and pharmacodynamic profiles were compared. RESULTS: Coadministration with alcohol did not alter the pharmacokinetics of alcohol or of sunobinop at either dose. A dose-effect relationship in the magnitude/duration of impairment in psychomotor/cognitive parameters was observed, with transient additive effects at 2 mg and greater-than-additive effects at 6 mg that resolved by 5 hours post administration. The most common treatment-emergent adverse event was somnolence, which was mild to moderate. CONCLUSIONS: A single oral dose of sunobinop was safe and tolerated alone and in combination with alcohol. No pharmacokinetic interaction between sunobinop and alcohol was observed. An additive or greater-than-additive effect was observed for psychomotor/cognitive measures consistent with sunobinop's sleep-promoting effect, and would peak and resolve during a typical night's sleep.