The Incidence of Abnormal Dreams and Nightmares in Adults With Insomnia Treated With Lemborexant: Results From Two Phase 3 Studies

Abstract: Introduction: Abnormal dreams and nightmares are reported by patients with insomnia both before and after treatment with hypnotics. Dual orexin receptor antagonists such as lemborexant (LEM) increase rapid eye movement sleep, during which dream content recall is more likely. We assessed the frequency of nightmares/abnormal dreams in subjects treated with LEM during two phase 3 studies. Methods: Study 303 (SUNRISE-2; NCT02952820) was a 12-month, randomized, double-blind, placebo (PBO)-controlled (first 6 months; Treatment Period [TP] 1), phase 3 study in subjects age ≥18 years with insomnia disorder and Insomnia Severity Index score ≥15. During TP1, the Safety Analysis Set (SAS) included: PBO, n=319; LEM 5 mg (LEM5), n=314; LEM 10 mg (LEM10), n=314 (%Female: 68.0%/66.2%/69.4%). Study 304 (SUNRISE-1; NCT02783729) was a 1-month, randomized, double-blind, PBO- and active-controlled (zolpidem tartrate extended-release 6.25 mg [ZOL]) study of LEM5 and LEM10. The SAS included: PBO, n=209; ZOL, n=263; LEM5, n=266; LEM10, n=268 (%Female: 89.0%/85.9%/85.7%/85.4%). Results: In Study 303 TP1, 28/947 subjects (3.0%) reported nightmares (n=12; PBO, n=1; LEM5, n=4; LEM10, n=7) or abnormal dreams (n=17; PBO, n=6; LEM5, n=7; LEM10, n=4) as treatment-emergent adverse events. In Study 304, 12/1006 subjects (1.2%) reported nightmares (n=4; PBO, n=1; ZOL, n=0; LEM5, n=2; LEM10, n=1) or abnormal dreams (n=8; PBO, n=1; ZOL, n=3; LEM5, n=0; LEM10, n=4); 32/40 (80.0%) of these subjects were female. Discussion: Abnormal dreams/nightmares were not common events in either study. Incidence was slightly higher with LEM10 and in females, consistent with a greater proportion of females being enrolled in both studies.Short Description: Abnormal dreams and nightmares are reported by patients with insomnia and those treated with hypnotics. We assessed the frequency of reports of nightmares/abnormal dreams in subjects treated with the dual orexin receptor antagonist lemborexant (LEM) during two Phase 3 studies. Abnormal dreams/nightmares were not common events. Incidence was slightly higher with LEM 10mg (vs LEM 5mg, placebo, and active control), and in females, consistent with a greater proportion of females being enrolled in both studies.Name of Sponsoring Organization(s): Eisai Inc.