Subjective ratings of medication strength of lemborexant over 6 months in subjects with moderate or severe insomnia
Recommended Citation
Drake C, Yardley J, Pinner K, Moline M. Subjective ratings of medication strength of lemborexant over 6 months in subjects with moderate or severe insomnia. J Sleep Res 2022; 31.
Document Type
Conference Proceeding
Publication Date
10-20-2022
Publication Title
J Sleep Res
Abstract
Objectives/Introduction: A concern with sedative-hypnotic medication to treat insomnia is 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, and were incorporated into the lemborexant (LEM) clinical program. LEM is a dual orexin receptor antagonist approved in multiple countries for the treatment of adults with insomnia. In Study E2006-G000-303 (Study 303; NCT02952820), significantly more subjects reported a positive effect of LEM versus placebo (PBO) at 1, 3 and 6 months, as assessed by PGI-I items 1-3. LEM-treated subjects also reported larger and statistically significant decreases in ISI versus PBO. In these post hoc analyses, potential tolerance to LEM was evaluated based on PGI-I item 4 (appropriateness of medication strength [responses: 1 = too strong, 2 = just right, 3 = too weak]) in subjects with moderate (ISI total score [ISI-TS] 15-21) or severe (ISI-TS 22-28) insomnia at baseline. Methods: Study 303 was a 12 months, double-blind, PBO-controlled (first 6 months), phase 3 study in subjects age ≥18 y with insomnia disorder and baseline ISI-TS ≥15. Subjects were randomized to PBO (n = 318), LEM 5 mg (LEM5; n = 316), or LEM 10 mg (LEM10; n = 315). PGI-I and ISI were administered at 1, 3, and 6 months. Results: Overall, 692 and 223 subjects had moderate or severe insomnia at baseline, respectively. The percentages of LEM-treated subjects (moderate/severe) who rated their medication strength as “just right” increased from 1mo (LEM5 = 46.4%/35.8%; LEM10 = 43.3%/40.6%; PBO = 31.3%/15.0%) to 6mo (LEM5 = 56.5%/54.8%; LEM10 = 53.9%/55.4%; PBO = 39.7%/21.6%). The majority of LEMtreated subjects who rated their medication strength as “just right” had ISI-TS ≤14 (subthreshold insomnia) at each of the time points. Ratings of “too weak” decreased from 1mo to 6mo (1, 6 months, LEM5: 47.9%/59.3%, 39.8%/41.9%; LEM10: 47.1%/50.7%, 37.7%/41.1%; PBO: 67.9%/83.3%, 58.8%/76.5%); percentages remained higher for PBO- than LEM-treated subjects. Ratings of “too strong” for LEM-treated subjects (moderate/severe) were low and stable over time (1mo, LEM5 = 5.7%/4.9%: LEM10 = 9.5%/8.7% and 6mo, LEM5 = 3.8%/3.2%: LEM10 = 8.4%/3.6%). Most adverse events were mild/moderate in severity. Conclusions: Findings from these analyses suggest that LEM tolerance does not develop over 6mo with either LEM dose in subjects with moderate or severe insomnia since the ratings of “too weak” did not increase over time.
Volume
31
