Subject-reported perception of long-term effectiveness of lemborexant versus placebo in nonelderly and elderly subgroups

Introduction: Demonstrating improvement from the patient\u27s perspective is an important objective for an insomnia treatment regimen to be regarded as successful. Clinical trials for insomnia therapies generally include outpatient data using daily sleep diaries to assess the magnitude of change in sleep onset and, in some cases, sleep maintenance outcomes. Instruments that assess patient perception of disease severity and symptom improvement can provide additional information on treatment effectiveness. Change in severity of insomnia symptoms is often assessed using the Insomnia Severity Index. The Patient Global Impression – Insomnia version (PGI‑I) is another self‑report questionnaire that evaluates subjects’ perception of the effects of a study medication on their sleep. The PGI-I does not have a baseline; therefore, the outcome is the global impression of the study medication\u27s effects during or at the end of treatment relative to their sleep prior to study enrollment. The PGI‑I contains 3 items related to study medication effects (helped/worsened sleep; decreased/increased time to fall asleep; and increased/decreased total sleep), rated on a 3‑point scale (1=positive, 2=neutral, 3=negative), and 1 item related to perceived appropriateness of study medication strength, rated on a different 3-point scale (1=too strong, 2=just right, 3=too weak). SUNRISE-2 (NCT02952820; E2006-G000-303) examined the efficacy and safety of lemborexant (LEM), a dual orexin receptor antagonist under development for the treatment of insomnia, vs placebo (PBO) in adult subjects with insomnia disorder. Here we present the results of the PGI-I at the end of 6 months of treatment based on age of subjects (\u3c65y [nonelderly] and ≥65y [elderly]). Methods: SUNRISE-2 was a Phase 3, 12-month, double-blind, global study in female and male adults aged ≥18y with insomnia disorder that included a 6-month PBO-controlled treatment period (after a PBO run-in) followed by a 6-month active-only treatment period. Subjects received PBO, LEM 5mg (LEM5) or LEM 10mg (LEM10) for the first 6 months. Titration to higher or lower doses was not possible. The PGI-I was administered at Months 1, 3, 6, 9, and 12; results from the end of PBO-controlled treatment are reported. Chi-square tests were used to compare the percentage of “positive” (or “just right”) responses with the combined “neutral” and “negative” (or combined “too strong” and “too weak”) response categories for LEM vs PBO subjects. Results: The full analysis set of SUNRISE-2 included 949 subjects. The subgroup of subjects \u3c65y included 687 (72.4%) subjects, with n=229 in each treatment group. The subgroup of subjects age ≥65y included 262 (27.6%) subjects, with 89, 87, and 86 subjects in the PBO, LEM5 and LEM10 groups, respectively. In the \u3c65y subgroup, significantly more subjects who received LEM5 or LEM10 versus subjects who received PBO reported that their study medication “helped” sleep (PBO, 49.4%; LEM5, 68.6% [P\u3c0.001]; LEM10, 70.7% [P\u3c0.0001]) and reduced time to fall asleep (PBO, 48.9%; LEM5, 71.9% [P\u3c0.0001]; LEM10, 72.5% [P\u3c0.0001]) at Month 6. Similarly, in the ≥65y subgroup, significantly more subjects who received LEM5 or LEM10, vs subjects who received PBO, reported that their study medication “helped” sleep (PBO, 35.0%; LEM5, 63.9% [P\u3c0.001]; LEM10, 64.2% [P\u3c0.001]) and reduced time to fall asleep (PBO, 40.0%; LEM5, 75.0% [P\u3c0.0001]; LEM10, 74.6% [P\u3c0.0001]) at Month 6. For both subgroups, significantly more LEM subjects reported an increase in total sleep time vs PBO subjects at Month 6 (\u3c65y subgroup: PBO, 43.3%, LEM5, 57.3% [P\u3c0.01], LEM10, 61.7% [P\u3c0.001]; ≥65y subgroup: PBO, 32.5%, LEM5, 59.7%, LEM10, 62.7% [P\u3c0.001, both comparisons]). Additionally, in the \u3c65y subgroup, a significantly greater percentage of subjects in the LEM5 and LEM10 groups selected that the treatment strength was “just right” vs PBO at Month 6 (PBO, 37.6%; LEM5, 53.0% [P\u3c0.01]; LEM10, 53.3% [P\u3c0.01]). Similarly, in the ≥65y subgroup, a significantly g eater percentage of subjects in the LEM5 and LEM10 groups selected that the treatment strength was “just right” vs PBO at Month 6 (PBO, 32.5%; LEM5, 62.5% [P\u3c0.001]; LEM10, 53.7% [P\u3c0.01]). LEM was well tolerated in both subgroups. The majority of treatment-emergent adverse events were mild or moderate. Conclusions: Overall, in both the \u3c65y and ≥65y subgroups, a greater number of LEM vs PBO subjects reported positive effects of their study treatment with regards to helping them sleep, reducing time to fall asleep, and total sleep time at Month 6. Thus, the positive subject perception of LEM effectiveness was consistent across age subgroups. The results of the PGI-I are also consistent with the benefits of LEM observed on sleep onset and maintenance outcomes as assessed by sleep diary data in SUNRISE-2. This research was funded by: Eisai, Inc