A randomized, double-blind, placebo-controlled, crossover study of respiratory safety of lemborexant in moderate to severe obstructive sleep apnea

Study Objectives: To evaluate the respiratory safety of lemborexant among adults and older adults with moderate to severe obstructive sleep apnea (OSA). Methods: E2006-A001-113 (Study 113; NCT04647383) was a double-blind, two-period crossover, placebo-controlled study in adults (ages >= 45 to <= 90 years, n = 33) with moderate (apnea-hypopnea index [AHI] score >= 15 to < 30 events/h, n = 13) or severe (AHI >= 30 events/h, n = 20) OSA. Participants were randomized to lemborexant 10 mg (LEM10) or placebo (PBO) for two treatment periods of 8 nights with a >= 14-day washout period. AHI and peripheral oxygen saturation were evaluated after treatment on Day 1 (after a single dose) and Day 8 (after multiple doses). Results: No significant differences in AHI were observed after single and multiple doses of LEM10 compared with PBO in participants with moderate to severe OSA (least-squares mean: single-dose LEM10, 41.7; PBO, 44.8; multiple-dose LEM10, 44.9; PBO, 45.7). In addition, there were no significant differences between treatments in peripheral oxygen saturation (least-squares mean: single-dose LEM10, 93.0; PBO, 93.1; multiple-dose LEM10, 93.1; PBO, 93.4). Further, there were no significant differences between treatments in percentage of total sleep time with peripheral oxygen saturation < 90%, < 85%, or < 80%. No significant differences were observed between treatments when AHI and peripheral oxygen saturation outcomes were analyzed by OSA severity. Altogether, 6/33 (18.2%) participants receiving LEM10, vs 3/33 (9.1%) PBO, reported treatment-emergent adverse events, mostly mild in severity. Conclusions: LEM10 demonstrated respiratory safety and was well tolerated with single-dose and multiple-dose administration in participants with moderate to severe OSA. This suggests that LEM may be a treatment option for patients with OSA and comorbid insomnia.