0364 The Effect of Lemborexant on Polysomnographic Sleep Parameters in Adults with Mild, Moderate, or Severe Obstructive Sleep Apnea

Abstract

Abstract Introduction Several commonly prescribed hypnotics may worsen respiratory function, especially in the elderly. Lemborexant (LEM) is a dual-orexin-receptor-antagonist approved to treat adults with insomnia. In Studies 102 (NCT03471871) and 113 (NCT04647383), LEM demonstrated respiratory safety in subjects with mild, moderate, or severe obstructive sleep apnea (OSA) who did not report insomnia. The current analyses evaluated sleep variables from these studies. Methods Studies 102 and 113 were double-blind, placebo (PBO)-controlled, crossover studies in adults with untreated mild (apnea-hypopnea-index [AHI] ≥5 to < 15), moderate (AHI≥15 to < 30), or severe (AHI≥30) OSA, without insomnia. Subjects were randomized to two 8-night periods (separated by ≥14 days) treated with LEM 10mg (LEM10) or PBO. Latency to persistent sleep (LPS), sleep efficiency (SE), and wake after sleep onset (WASO) were assessed using polysomnography on Days 1 (D1) and 8 (D8). Results The analysis set comprised 39, 13, and 20 subjects with mild, moderate, or severe OSA, respectively. On both days, LPS was not statistically different from PBO in any group. Compared with PBO, SE was significantly greater on D1 in subjects with mild (LEM10, 90.43; PBO, 80.31; P< 0.0001), moderate (LEM10, 88.83; PBO, 84.02; P=0.016), and severe (LEM10, 87.76; PBO, 77.84; P< 0.0001) OSA. On D8, SE was significantly greater in subjects with mild (LEM10, 86.65; PBO, 80.59; P=0.003) and moderate (LEM10, 88.45; PBO, 80.70; P=0.004) OSA, with a trend towards significance in subjects with severe (LEM10, 85.60; PBO, 80.63; P=0.055) OSA. WASO was significantly lower (improved) on D1 in subjects with mild (LEM10, 33.30; PBO, 76.76; P< 0.0001), moderate (LEM10, 44.26; PBO, 64.71; P=0.008), and severe (LEM10, 42.03; PBO, 91.49; P< 0.0001) OSA. On D8, WASO was significantly lower in subjects with mild (LEM10, 51.74; PBO, 70.52; P=0.015) and moderate (LEM10, 49.16; PBO, 75.15; P=0.008) but not severe (LEM10, 59.85; PBO, 74.46; P=0.161) OSA. LEM was well-tolerated. Conclusion In untreated OSA subjects without insomnia, irrespective of OSA severity, LEM improved sleep maintenance versus PBO. LPS did not differ between treatments since such patients may not report sleep onset difficulties. These findings support the use of LEM for patients with comorbid insomnia and sleep apnea (COMISA). Support (if any) Eisai, Inc.