This study examined the effects of lemborexant (LEM) compared with placebo (PBO) on subject-reported insomnia disease severity, assessed by the Insomnia Severity Index (ISI), and fatigue, assessed by the Fatigue Severity Score (FSS), from the 6-month PBO-controlled period of SUNRISE-2.
SUNRISE-2 (NCT02952820; E2006-G000-303) was a 12-month randomized, double-blind, PBO-controlled (first 6-months) Phase 3 study. After an ~2-week PBO run-in, subjects were randomized to PBO, LEM 5mg (LEM5) or LEM 10mg (LEM10) for 6 months. The ISI and the FSS were administered at baseline [BL] and at the end of Months 1, 3, and 6. The ISI daytime functioning score (DFS), based on the ISI items that assess the impact of insomnia symptoms specific to daily functioning (items 4-7), was also evaluated. Mean changes from BL in ISI total score (ISI TS), ISI DFS, and FSS total score (FSS TS) were analyzed using a mixed-effect model repeated measurement analysis, adjusted for relevant factors and BL score (ISI TS, ISI DFS, or FSS TS) as a covariate.
949 subjects (PBO, n=318; LEM5, n=316; LEM10, n=315) were included in the full analysis set. Median age was 55y (range 18-88y). Mean ISI TS at BL for PBO, LEM5, and LEM10 was 19.0, 19.6 and 19.1, respectively. While mean ISI TS decreased (improved) from BL for all groups, decreases were significantly larger for both LEM5 and LEM10 vs PBO at Month 1 (least squares mean treatment difference [LSM TD]: LEM5, −1.5 [P=0.001]; LEM10, −1.9 [P<0.0001]), Month 3 (LSM TD: LEM5, −2.0; LEM10, −2.6 [both P<0.0001]), and Month 6 (LSM TD: LEM5, −2.1; LEM10, −2.4 [both P<0.0001]). Decreases from BL in mean ISI DFS were also significantly larger for LEM5 and LEM10 vs PBO at Month 1 (LSM TD: LEM5, −0.7 [P=0.014]; LEM10, −0.9 [P=0.001]), Month 3 (LSM TD: LEM5, −1.2 [P=0.0001]; LEM10, −1.4 [P<0.0001]), and Month 6 (LSM TD: LEM5, −1.3; LEM10, −1.3 [both P<0.0001]).
Mean FSS TS at BL was 35.2, 37.4, and 36.0 for PBO, LEM5, and LEM10, respectively. Mean FSS TS decreased (improved) from BL in all groups at the end of Month 1 (decreases were larger and significant for LEM10 vs PBO [LSM TD: –2.0 (P=0.026)]), and Month 3 (decreases were larger and significant for LEM5 [LSM TD: –2.2 (P=0.021)] and LEM10 [LSM TD: –3.0; (P=0.001)] vs PBO). At Month 6, mean FSS TS remained improved from BL in all treatment groups (PBO, –6.3; LEM5, –10.1; and LEM10, –8.9). These decreases were larger and significant for LEM5 (LSM TD: –2.5 [P=0.013]) and LEM10 (LSM TD: –2.6 [P=0.013]) vs PBO. LEM was well tolerated with most adverse events mild to moderate in severity.
In SUNRISE-2, LEM5 and LEM10 significantly reduced subject-reported disease severity and fatigue vs PBO after 6 months of treatment. Reduced severity in insomnia symptoms with LEM5 and LEM10 also translated to improved daytime functioning.