Efficacy and safety of a selective partial agonist for nociception/orphanin-FQ peptide (NOP) receptors in patients with insomnia disorder

Abstract

Aims: Insomnia is a common sleep disorder, affecting up to 20% of the world population and adversely impacting productivity, health, and overall well-being. Although pharmacologic options exist to treat insomnia, the health-related quality of life for patients who are prescribed hypnotics is no higher than for those who are not, revealing a significant treatment gap. Sunobinop, an oral, selective, potent, partial agonist of the nociceptin receptor (NOP), was evaluated for efficacy and safety in the treatment of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) insomnia disorder. Methods: In this randomized, double-blind, repeat-dose, crossover, Phase 1 study, 30 patients were assigned to treatment with sunobinop 0.5 mg, 1.0 mg, 3.0 mg and 6.0 mg and placebo; changes in sleep parameters, measured by polysomnography (PSG), in addition to subjective sleep measures and safety-related measures were assessed. Twenty-nine patients completed the study. Results: Sunobinop demonstrated a dose-dependent and significant increase in sleep efficiency compared with placebo. Sleep efficiency was statistically significantly increased by 12.1%, 14.7%, 17.6% and 19.0% over baseline at 0.5 mg, 1.0 mg, 3.0 mg and 6.0 mg, respectively (P ≤ 0.001) compared to placebo. Sunobinop improved sleep maintenance, measured by wakefulness after sleep onset, at all doses compared with placebo. Sunobinop resulted in a significant dose-dependent change in time spent in N1 and N2 sleep with no effect on rapid eye movement (REM) latency, differentiating sunobinop from other hypnotics. Results from PSG measures correlated well with those from subjective assessments. Adverse events (AEs) that occurred in this study were rated by investigators as largely mild. Conclusions: In this Phase 1 study of 30 patients, sunobinop was well tolerated by patients, with no study discontinuation due to AEs. Doses were identified that had a beneficial effect on sleep measures without eliciting next-day residual effects (<3 mg). These data suggest that sunobinop has the potential to be developed as a therapeutic option for the treatment of sleep disturbances, including DSM-5 insomnia; however, larger confirmatory studies are warranted.