0353 Effect of Lemborexant on Sleep Architecture in Adult and Elderly Subjects with Mild to Severe Obstructive Sleep Apnea

Abstract

Abstract Introduction Lemborexant (LEM) is a dual-orexin-receptor antagonist approved to treat adults with insomnia. In such patients, LEM increased total sleep, with prominent increases in rapid eye movement (REM). Since patients with obstructive sleep apnea (OSA) may report sleep difficulties and show decreased REM sleep, sleep architecture was analyzed after treatment with LEM. Methods Studies 102 and 113 were double-blind, placebo (PBO)-controlled crossover studies in adult and elderly subjects with mild (apnea-hypopnea index [AHI] ≥5 to < 15) or moderate (AHI ≥15 to < 30)/severe (AHI ≥30) OSA, respectively, without insomnia. Subjects were randomized to LEM 10mg (LEM10) or PBO in two 8-night treatment periods (separated by ≥14 days). Least-squares-mean (LSM) for each sleep stage (minutes) was compared across conditions on Days 1 (D1) and 8 (D8). Treatment-emergent adverse events (TEAEs) were recorded. Results The analysis set comprised 39 subjects with mild OSA and 33 with moderate/severe OSA. On both days, total sleep time was significantly higher in the LEM condition in subjects with mild (D1: LEM10, 434.08; PBO, 385.46; P< 0.0001; D8: LEM10, 415.90; PBO, 386.85; P=0.003) and moderate/severe (D1: LEM10, 423.10; PBO, 385.48; P< 0.0001; D8: LEM10, 416.96; PBO, 385.57; P=0.001) OSA. Compared with PBO, total non-REM sleep significantly increased only on D1 in subjects with mild OSA (D1: LEM10, 330.57; PBO, 308.55; P=0.001; D8: LEM10, 323.77; PBO, 308.97; P=0.060) but on both days in subjects with moderate/severe OSA (D1: LEM10, 343.23; PBO, 327.45; P=0.006; D8: LEM10, 341.83; PBO, 322.48; P=0.018). Total REM sleep significantly increased in subjects with mild (D1: LEM10, 103.59; PBO, 76.91; P< 0.0001; D8: LEM10, 92.13; PBO, 77.93; P=0.004) and moderate/severe (D1: LEM10, 79.87; PBO, 58.03; P< 0.0001; D8: LEM10, 75.13; PBO, 62.69; P=0.006) OSA. REM latency was significantly decreased on both days in subjects with mild OSA (D1: LEM10, 51.96; PBO, 83.36; P< 0.0001; Day 8: LEM10, 67.52; PBO, 102.34; P=0.005) and only on D1 in subjects with moderate/severe OSA (D1: LEM10, 72.13; PBO, 98.90; P=0.029; D8: LEM10, 90.42; PBO, 106.63; P=0.242). LEM was well-tolerated; most TEAEs were mild. Conclusion In OSA subjects without insomnia, LEM nevertheless increased total sleep, non-REM, and REM sleep versus PBO. Support (if any) Eisai Inc.