Objective:

To evaluate sleep parameters with lemborexant (LEM) versus zolpidem tartrate extended-release 6.25mg (ZOL) in subjects with insomnia and objective short-sleep duration (I-SSD), defined as total sleep time (TST) <6h.

Background:

There is evidence that patients with I-SSD may be less responsive to behavioral therapy for insomnia compared with insomnia patients with objectively longer, more normal sleep duration (TST ≥6h).

Design/Methods:

In Study E2006-G000-304 (NCT02783729), subjects (females age≥55y; males age≥65y) were randomized to LEM 5mg (LEM5) or 10mg (LEM10), placebo (PBO), or ZOL. Latency to persistent sleep (LPS) and wake after sleep onset (WASO) were assessed using polysomnograms and averaged. Change from baseline (paired polysomnograms during single-blind PBO run-in) was analyzed using mixed-effect model repeated measurement analysis for pooled Nights (NT)1/2 and NT29/30.

Results:

The I-SSD subgroup comprised 710/1006 (70.6%) subjects. Mean(SD) baseline LPS was similar across treatments in this subgroup: LEM5=54.28(39.30), LEM10=53.31(34.45), PBO=52.80(35.73), ZOL=54.77(40.93). At NT1/2, LEM5/LEM10 led to significant (P<0.05) decreases from baseline (LEM5=−22.02[31.62], LEM10=−25.42[34.73], PBO=−9.65[36.52], ZOL=−17.78[36.34]) versus PBO and ZOL. At NT29/30, LEM5/LEM10 led to significant (P<0.0005) decreases from baseline (LEM5=−25.37[37.06], LEM10=−28.20[34.75], PBO=−11.88[35.09], ZOL=−12.57[38.50]) versus PBO and ZOL, and LPS with ZOL was not different than PBO. Mean(SD) baseline WASO was similar across treatments: LEM5=128.14(37.52), LEM10=129.07(37.98), PBO=123.79(37.21), ZOL=128.37(38.94). At NT1/2, LEM5/LEM10 led to significant (P<0.0001) decreases from baseline (least squares mean[SE]: LEM5=−60.58[2.45]; LEM10=−69.35[2.41], PBO=−23.52[2.74], ZOL=−54.74[2.47]) versus PBO, and LEM10 was significantly different versus ZOL (P<0.0001). At NT29/30, LEM5/LEM10 led to significant (P<0.0001) decreases from baseline (LEM5=−52.67[2.74], LEM10=−55.37[2.70], PBO=−29.62[3.09], ZOL=−46.86[2.80]) versus PBO, and LEM10 decreases were significantly different versus ZOL (P<0.05).

Conclusions:

These results support LEM as an effective therapy for older patients with I-SSD and suggest LEM may be more beneficial than ZOL in these patients. Thus, LEM may be reasonably considered for treating older patients with I-SSD where behavioral therapy may have relatively limited efficacy.