In phase 3 Study E2006-G000-304 (Study 304; NCT02783729), LEM improved polysomnographic (PSG) endpoints and sleep diary-based outcomes over 1mo in subjects with insomnia disorder. The study included the ISI to ensure sufficient insomnia severity at baseline (ISI total score [ISI-TS] ≥13). Since subjects with insomnia with I-SSD (<6 hours total sleep time [TST] per night) may respond less well to therapeutic approaches such as cognitive behavioral therapy for insomnia (CBT-I), we examined rates of response and remission in this subgroup.

In Study 304, subjects (females ≥55 years; males ≥65 years) were randomized to LEM 5 mg (LEM5) or 10 mg (LEM10), placebo (PBO), or zolpidem extended release (not reported) for 1mo. Paired baseline PSGs were obtained during a single-blind PBO run-in, followed by paired PSGs on Nights 1/2 and Nights 29/30. Responders were defined as subjects with ISI-TS ≥7 points decrease from baseline to end of treatment, while remitters achieved ISI-TS <8 points.

525/743 (70.7%) subjects in the PBO/LEM groups were in the I-SSD subgroup. For LEM5, 100/178 (56.2%) were responders, and 50/178 (28.1%) were remitters. For LEM10, 97/180 (53.9%) were responders, and 50/180 (27.8%) were remitters. For PBO, 58/138 (42.0%) were responders and 20/138 (14.5%) were remitters. The responder and remitter rates for LEM5 and LEM10 were significantly greater than those for PBO (all P<0.05). LEM was well tolerated with most treatment-emergent adverse events mild/moderate in severity.

Older adults with I-SSD achieved clinically meaningful improvement with LEM at the end of 1mo of treatment, with nearly 30% considered remitters and >50% considered treatment responders. LEM is a potential therapy for patients with I-SSD, including those with limited response to CBT-I.