0449 Correlations Between Sleep Parameters and ISI Total Score in Subjects with Moderate to Severe Insomnia Treated with Lemborexant

Abstract

Abstract Introduction Lemborexant (LEM) is a dual orexin receptor antagonist (DORA) approved in multiple countries for the treatment of adults with insomnia. In Study 303 (NCT02952820), LEM provided significant benefit on subject-reported sleep measures versus placebo (PBO). This post hoc analysis investigated whether changes from baseline in sleep parameters with LEM are correlated with insomnia disorder severity. Methods Study 303 was a randomized, double-blind, PBO-controlled (first 6mo [Period 1]), phase 3 study. During Period 1, subjects received LEM 5mg (LEM5), LEM 10mg (LEM10), or PBO. During Period 2 (second 6mo), LEM subjects continued their assigned dose and PBO subjects were rerandomized to LEM5 or LEM10 (rerandomized subjects not reported here). The correlation between changes in subject-reported sleep parameters (sleep onset latency [sSOL], wake after sleep onset [sWASO], sleep efficiency [sSE], total sleep time [sTST]) and insomnia disorder severity, as assessed by the Insomnia Severity Index total score (ISI-TS) were evaluated in the Full Analysis Set (FAS; ISI-TS ≥15) and in a subgroup of subjects with severe (ISI-TS ≥22 at baseline) insomnia over 12mo for LEM and over 6mo for PBO. Results Among 949 (PBO=318; LEM5=316; LEM10=315) subjects, 223 (PBO=65; LEM5=84; LEM10=74) had severe insomnia at baseline. Within each sleep parameter and severity group, baseline values were similar across treatments. Overall, strong to very strong correlations were observed between changes from baseline in sleep parameters and decrease in ISI-TS, regardless of treatment, as determined by correlation coefficients for sSOL (LEM5=0.973 [P=0.0053]; LEM10=0.997 [P=0.0002]; PBO=0.844 [P=0.361]), sSE (LEM5=–0.937 [P=0.0188]; LEM10=–0.992 [P=0.0008]; PBO=–0.950 [P=0.2018]), sWASO (LEM5=0.937 [P=0.0187]; LEM10=0.996 [P=0.0003]; PBO=0.979 [P=0.1299]), and sTST (LEM5=–0.876 [P=0.0515]; LEM10=–0.974 [P=0.0050]; PBO=–0.933 [P=0.2346]). Strong to very strong correlations were also observed in subjects with severe insomnia: sSOL (LEM5=0.818 [P=0.0904]; LEM10=0.823 [P=0.0868]; PBO=0.828 [P=0.3788]), sSE (LEM5=–0.860 [P=0.0616]; LEM10=–0.975 [P=0.0048]; PBO=–0.961 [P=0.1792]), sWASO (LEM5=0.871 [P=0.0544]; LEM10=0.936 [P=0.0194]; PBO=0.875 [P=0.3213]), and sTST (LEM5=–0.843 [P=0.0729]; LEM10=–0.969 [P=0.0095]; PBO=–0.974 [P=0.1449]). Conclusion Across the study period, changes from baseline in reported nocturnal sleep parameters correlated with reductions in severity of insomnia disorder regardless of insomnia severity at baseline. Support (If Any) Eisai Inc.