Evaluation of sunobinop for next-day residual effects in healthy participants

Abstract

Sunobinop is a novel, potent, selective partial agonist at nociceptin/orphanin FQ peptide (NOP) receptors. The primary objective of this randomized, double-blind, placebo-controlled study was to assess the next-day residual effects of an evening dose of sunobinop in healthy participants. Participants were randomized into 1 of 5 treatment sequences. Treatment consisted of 1 dose each of sunobinop 0.2, 0.6, 2, and 6 mg suspension and placebo suspension. Key pharmacodynamic (PD) measures included the digit symbol substitution test (DSST), Karolinska sleepiness scale (KSS), and body sway. The randomized safety population consisted of 25 participants. The DSST, KSS, and body sway showed dose-dependent effects following the administration of sunobinop, with no significant differences versus placebo at sunobinop doses <2 mg. At sunobinop 2 mg, PD effects were relatively small in magnitude and inconsistent. The last timepoint where significant differences between sunobinop 2 mg and placebo on the DSST, KSS, and body sway were observed was at 12 h, 16.5 h, and 13.5 h postdose, respectively. Sunobinop 6 mg resulted in larger and consistent PD effects, with significant differences from placebo at all timepoints up to 16.5-18 h postdose. Somnolence was the most frequently reported adverse event (AE), and all AEs were mild-to-moderate. No deaths occurred during the study or discontinuations due to an AE. Overall, a nighttime oral dose of sunobinop up to 2 mg was safe and generally well tolerated in healthy participants with limited next-day residual effects that were consistent with other sedative/hypnotic drugs.

Keywords: healthy participants; insomnia; next-day residual effects; nociceptin/orphanin FQ; sunobinop.

FIGURE 1

Study design. EOS, end of study; SD, study drug; TC, telephone call. During the 5 treatment periods, all participants were administered a placebo on day 1 for acclimatization to the overnight laboratory environment and active treatment on day 2, per the randomized schedule. There was a minimum washout of approximately 5 days between successive treatment periods. Subjects were confined to the study unit from check-in of each period to the morning of day 4 in each period. EOS procedures were performed before discharge for all participants, including those who discontinued the study. A follow-up telephone call was conducted after EOS or after early withdrawal. The total study duration was up to approximately 64 days.

FIGURE 2

DSST scores vs. time by treatment. ^* p < .05 compared with placebo. CI, confidence interval; DSST, digit symbol substitution test; LSM, least squares mean. The DSST showed a dose-dependent decrease in correct responses with active treatment, indicating an effect on attention and psychomotor speed.

FIGURE 3

KSS vs. time by treatment. ^* p < .05 compared with placebo. CI, confidence interval; KSS, Karolinska sleepiness scale, LSM, least squares mean. The KSS scores showed a dose-dependent increase in feelings of sleepiness with active treatment.

FIGURE 4

Body sway vs. time by treatment. ^* p < .05 compared with placebo. CI, confidence interval; LSM, least squares mean. The body sway test showed a dose-dependent increase in instability with active treatment, indicating worse postural stability.