0388 Lemborexant Effect on Sleep Parameters in Adults with Moderate or Severe Chronic Obstructive Pulmonary Disease

Abstract Introduction Several commonly prescribed hypnotics may worsen respiratory function, especially in the elderly. Lemborexant (LEM) is a competitive dual-orexin-receptor-antagonist approved to treat adults with insomnia. In Study E2006-A001-113 (NCT04647383), LEM demonstrated respiratory safety in participants with untreated moderate-to-severe chronic obstructive pulmonary disease (COPD). This post hoc analysis evaluated sleep variables from this study. Methods This double-blind, placebo (PBO)-controlled, crossover study enrolled adults (45–90y) with untreated moderate or severe COPD, assessed by Global Initiative for Obstructive Lung Disease spirometry recommendations (apnea hypopnea index 15 was allowed). Participants were randomized to LEM 10mg (LEM10) or PBO in two 8-night treatment periods (separated by ≥14d). Latency to persistent sleep (LPS), sleep efficiency, wake after sleep onset (WASO), and total-sleep-time (TST) were assessed using in-laboratory polysomnography on Days 1 (D1) and 8 (D8). Results The analysis set comprised 30 adults with moderate (n=25) or severe (n=5) COPD (mean SD age, 69.2 6.3y; 70.0% female). Six (20%) participants had a medical history of insomnia. Least squares mean (LSM; standard error SE) LPS was significantly shorter (improved) with LEM10 compared with PBO on D1 (LEM10, 30.9 9.0 min; PBO, 51.5 9.0 min; P 0.01) and D8 (LEM10, 27.0 7.0 min; PBO, 46.6 7.0 min; P 0.001). LSM (SE) sleep efficiency was significantly higher (improved) with LEM10 compared with PBO on D1 (LEM10, 81.0% 2.6%; PBO, 66.6% 2.6%; P 0.0001) and D8 (LEM10, 77.1% 2.9%; PBO, 69.4% 2.9%; P 0.0001). LSM (SE) WASO was significantly lower (improved) with LEM10 compared with PBO on D1 (LEM10, 68.2 9.6 min; PBO, 114.6 9.6 min; P 0.0001) and D8 (LEM10, 90.4 9.9 min; PBO, 106.1 9.9 min; P 0.0001). LSM (SE) TST was significantly longer (improved) with LEM10 compared with PBO on D1 (LEM10, 388.9 12.4 min; PBO, 319.5 12.4 min; P 0.0001) and D8 (LEM10, 370.1 13.7 min; PBO, 332.9 13.7 min; P 0.0001). LEM was well-tolerated. Conclusion In participants with untreated moderate-to-severe COPD, most of whom did not have a medical history of insomnia, LEM improved sleep onset, sleep maintenance, and TST compared with PBO, suggesting LEM may be a potential treatment option for patients with COPD and insomnia. Support (if any) Eisai, Inc.