Recent Findings on Daridorexant for Menopausal Women with Insomnia
A recent subgroup analysis from a large-scale phase 3 clinical trial (NCT03545191) has provided new insights into the efficacy of daridorexant (Quivivq; Idorsia) for treating insomnia in women undergoing menopausal transition. Specifically, the study indicated that the 50 mg dosage of daridorexant may effectively enhance sleep onset, sleep maintenance, and overall daytime functioning in this demographic.
Key Study Insights
Presented at the World Sleep Congress, held in Singapore from September 5-10, these findings represent the inaugural evaluation of daridorexant in women grappling with insomnia related to menopause. Daridorexant, which received FDA approval in 2022, belongs to the dual orexin receptor antagonist (DORA) class of medications, functioning by obstructing the action of orexin-A and orexin-B neuropeptides.
Study Design and Results
The post-hoc analysis evaluated women aged 47 to 55 years participating in the larger phase 3 trial. Participants were assigned to receive either daridorexant at 50 mg (n = 35), 25 mg (n = 43), or a placebo (n = 39). The results indicated significant reductions in wake after sleep onset (WASO) at months 1 and 3. Notably, the higher 50 mg dosage exhibited the most substantial effects:
- Month 1: 50 mg group: least square mean (LSM) change of –42.4 minutes (95% CI, –52.5 to –32.3); placebo: –12.7 minutes (95% CI, –22.4 to –3.0)
- Month 3: 50 mg group: –42.9 minutes (95% CI, –53.5 to –32.3); placebo: –29.1 minutes (95% CI, –40.0 to –18.3)
Continued analysis revealed further improvements in latency to persistent sleep (LPS) and self-reported total sleep time (sTST). At month 3, the changes in LPS and sTST for the 50 mg group were both greater than those observed in the placebo and 25 mg groups:
- LPS: –34.2 minutes (50 mg) vs. –23.3 minutes (placebo)
- sTST: 75.3 minutes (50 mg) vs. 53.5 minutes (placebo)
Daytime Functionality and Safety Assessment
Led by menopause specialist Zoe Schaedel, MRCGP, DRCOG, the study also analyzed effects on insomnia-related daytime impairment using the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Here, the 50 mg dosage showed notable improvements:
- Month 1: LSM change of –14.7 (95% CI, –20.4 to –8.9)
- Month 3: LSM change of –21.9 (95% CI, –29.3 to –14.5)
Regarding safety, treatment-emergent adverse events (TEAEs) were recorded in 46% of patients receiving the 50 mg dose, 35% in the 25 mg group, and 38% in the placebo group. A total of two serious adverse events (AEs) and two TEAEs leading to discontinuation occurred, all within the placebo cohort. The most common TEAE was nasopharyngitis, with occurrences in:
- 11% of the 50 mg group
- 5% of the 25 mg group
- 13% of the placebo group
Other reported AEs included headache, gastroenteritis, back pain, influenza, and somnolence, though these were relatively infrequent across all groups.
Morning Sleepiness Improvements
The Visual Analogue Scale (VAS), used to assess morning sleepiness, displayed improvements from baseline to both months 1 and 3 for all groups. Specifically, the three-month mean changes were as follows:
- 50 mg group: 14.1 (SD 18.5)
- 25 mg group: 14.8 (SD 19.3)
- Placebo group: 15.7 (SD 20.6)
In this context, higher VAS scores indicated reduced morning sleepiness.
Conclusion
The findings from this analysis contribute valuable knowledge regarding the potential benefits of daridorexant for managing insomnia in menopausal women, highlighting its efficacy in enhancing sleep quality and daytime functioning while providing a safety profile consistent with existing treatments.
For further details, refer to the study by Schaedel et al. presented at the World Sleep Congress.
