Understanding daytime functioning in insomnia: responder and correlation analyses in patients treated with daridorexant

Abstract

Abstract Background Improving daytime functioning is a key treatment goal for patients with insomnia disorder. In a phase 3 study, using the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), daridorexant 50 mg significantly improved daytime functioning in adults with insomnia, as well as sleep parameters. These data are further analyzed to evaluate the clinically meaningful changes in IDSIQ scores at weekly intervals and investigate the correlation between the effects of daridorexant on daytime functioning and on sleep quality and quantity. Methods Nine hundred thirty patients with insomnia randomized to daridorexant 25 mg (n = 310), 50 mg (n = 310) or placebo (n = 310) for 12 weeks were analyzed, with focus on daridorexant 50 mg and placebo. Patients recorded daily their daytime functioning using the IDSIQ and their self-reported total sleep time (sTST) and sleep quality using a sleep diary questionnaire; weekly mean changes from baseline were calculated. A clinically meaningful improvement (‘response’) at a given week was defined as a ≥ 20-point decrease in IDSIQ total score from baseline. Results Weekly responder rates increased over time in both groups but were consistently higher each week with daridorexant. Overall, 53% (n = 165/310) of patients in the daridorexant 50 mg group perceived a response for ≥ 1 week versus 41% in the placebo group (n = 126/310). This response, which could be achieved at any time during the 12 weeks of the study, was more often continuous on daridorexant and more often intermittent on placebo. Time-to-first response was significantly different between daridorexant and placebo (hazard ratio 1.55; 95% confidence intervals [CI] 1.22, 1.97; p = 0.0003) with shorter time observed in daridorexant. Patient perception of the response also lasted longer on daridorexant than placebo (mean number of continuous responder weeks; 9.2 vs. 7.9 respectively). A decrease in IDSIQ total score was correlated with an increase in sTST and sleep quality and a decrease in morning sleepiness, from Week 1 onwards. Conclusion Patients with insomnia are more likely to perceive a clinically meaningful improvement in their daytime functioning each week with daridorexant 50 mg than placebo. The response, which can fluctuate over time, is also perceived earlier and sustained for longer than placebo. The correlations between improved daytime functioning and improved sleep quantity and quality support the benefits of daridorexant on both the night and daytime symptoms in patients with insomnia disorder. Trial registration ClinicalTrials.gov: NCT03545191.