Phase 1b/2a safety study of lemborexant as an adjunctive treatment for insomnia to buprenorphine-naloxone for opioid use disorder: A randomized controlled trial

Abstract

Background

Evidence supports the common incidence of sleep disturbance in opioid use disorder (OUD) as a potential marker of disrupted orexin system functioning. This study evaluated the initial safety and tolerability of a challenge dose of lemborexant, a dual orexin antagonist, as an adjunct to buprenorphine/naloxone.

Methods

Patients (18–65 years old) with OUD receiving sublingual buprenorphine/naloxone, with a Pittsburgh Sleep Quality Index total score of 6 or higher, were recruited from outpatient clinics. After randomization, while being monitored on an inpatient research unit over two 10-hour daytime periods, participants received a placebo or lemborexant (5 mg on day one and 10 mg on day two) along with buprenorphine/naloxone. Primary outcomes included safety and tolerability: adverse events, physiologic measures, sedation level assessments. Generalized linear mixed model analysis assessed the effect of study drug and time on outcomes.

Results

N=18 (14=male, 4=female) were randomized to lemborexant (n=12) or placebo (n=6). No unanticipated problems occurred; five adverse events occurred in the lemborexant group and two in the placebo group with no serious adverse events. None of the physiologic measures showed a significant interaction of time and placebo vs. lemborexant (5 or 10 mg): Pulse oximetry (F=0.6; p=0.84), End-tidal CO2 (F=0.5; p=0.91), Heart rate (F=0.6; p=0.82), Systolic blood pressure (F=0.7; p=0.73), Diastolic blood pressure (F=2.0; p=0.06). At 9 hours after study drug administration, all participants returned to baseline sedation levels and were discharged.

Conclusions

Findings support the initial safety and tolerability of lemborexant as an adjunctive treatment for insomnia in humans receiving buprenorphine for OUD. Future longitudinal work is warranted with larger samples.