Subjective Ratings of Medication Strength of Lemborexant Over 6 Months in Subjects With Moderate or Severe Insomnia

Abstract: Introduction: A concern with sedative-hypnotic medication for the treatment of insomnia is the development of tolerance. The Patient Global Impression–Insomnia (PGI-I) and Insomnia Severity Index (ISI) assess patients’ perceptions of medication effectiveness/strength and insomnia severity, respectively. Lemborexant (LEM) is a dual orexin receptor antagonist approved for the treatment of adults with insomnia. In post-hoc analyses of Study E2006-G000-303 (Study 303; NCT02952820), potential tolerance to LEM 5-mg (LEM5) or 10-mg (LEM10) was evaluated based on PGI-I item 4 (appropriateness of medication strength) in subjects with moderate/severe insomnia at baseline. Methods: Study 303 was a 12-month, double-blind, randomized, placebo (PBO)-controlled (first 6-months) phase 3 study in subjects age ≥18 years with insomnia disorder and baseline ISI total score (ISI-TS) ≥15. Subjects received PBO (n=318), LEM5 (n=316), or LEM10 (n=315). PGI-I and ISI were administered at 1, 3, and 6-months. Results: Overall, 692 and 223 subjects had moderate and severe insomnia at baseline, respectively. Percentages of LEM-treated subjects (moderate/severe) who rated their medication strength as “just right” increased from 1-month (LEM5=46.4%/35.8%; LEM10=43.3%/40.6%; PBO=31.3%/15.0%) to 6-months (LEM5=56.5%/54.8%; LEM10=53.9%/55.4%; PBO=39.7%/21.6%); most subjects had ISI-TS ≤14 (subthreshold insomnia) at each time point. Ratings of “too weak” decreased from 1-month to 6-months; percentages remained higher for PBO than LEM-treated subjects. For LEM-treated subjects, ratings of “too strong” were low and stable over time. Most adverse events were mild/moderate in severity. Discussion: Tolerance to LEM apparently does not develop over 6-months in subjects with moderate/severe insomnia since the ratings of “too weak” did not increase over time.Short Description: The Patient Global Impression–Insomnia (PGI-I) and Insomnia Severity Index (ISI) assess patients’ perceptions of medication effectiveness and insomnia severity, respectively. Post-hoc analyses of Study 303 (NCT02952820) in subjects with moderate or severe insomnia evaluated the potential for tolerance to lemborexant (LEM) using both PGI-I and ISI. Findings suggest that tolerance to LEM did not develop over 6 months since medication-strength ratings of “too weak” did not increase over time.Name of Sponsoring Organization(s): Eisai Inc.