Effectiveness and Safety of Lemborexant in Subjects Previously Treated with Placebo for 6 Months in SUNRISE-2

 Introduction: In Study 303 (SUNRISE-2; NCT02952820), while lemborexant (LEM) provided significant benefit versus placebo (PBO) on sleep-diary measurements over 6mo, some improvement was noted in PBO subjects. We report outcomes from PBO subjects rerandomized to LEM during the last 6mo. 

Methods: Study 303 was a randomized, double-blind, global phase 3 study in adults (≥18y) with insomnia disorder. Subjects received PBO or LEM (5mg [LEM5]; 10mg [LEM10]) for 6mo (Treatment Period 1). PBO subjects were rerandomized to LEM for another 6mo; LEM subjects continued assigned treatment (Treatment Period 2). Changes from the 6mo baseline were calculated after PBO completion.

Results: At study baseline, median sSOL(min) was 55.9 and mean[SD] sSE(%) and sWASO(min) were 61.3[17.8] and 132.5(80.2), respectively, for PBO subjects (n=318). The 6mo baseline values for rerandomized PBO-LEM5 (n=133) and PBO-LEM10 (n=125) subjects, respectively, were: median sSOL, 31.2, 34.3; mean[SD] sSE, 70.5[20.2], 71.1[18.0]; mean[SD] sWASO, 105.1[80.6], 100.1[84.6]. Median sSOL further decreased from the 6mo baseline after 1mo (PBO-LEM5, −3.2; PBO-LEM10, −2.9) and 6mo (PBO-LEM5, −2.7; PBO-LEM10, −5.0). Mean[SD] sSE further increased from the 6mo baseline after 1mo (PBO-LEM5, 3.9[12.1]; PBO-LEM10, 3.5[8.1]) and 6mo (PBO-LEM5, 3.9[13.6]; PBO-LEM10, 4.5[13.0]). Mean[SD] sWASO further decreased after 1mo (PBO-LEM5, −8.5[49.4]; PBO-LEM10, −5.7[36.1]) and 6mo (PBO-LEM5, −8.2[49.0]; PBO-LEM10, −10.0[58.8]). Treatment-emergent adverse events incidence was similar during PBO (62.7%) and LEM treatment (PBO-LEM5, 54.9%; PBO-LEM10, 57.7%) and consistent with those observed in subjects originally randomized to LEM.

Conclusions: Rerandomization to LEM was associated with additional and sustained improvement in sleep outcomes following the PBO-related response.