No Daytime Grogginess Observed With Menopause Hot Flash Drug

— Post-hoc analysis suggests that sleep benefits don't come at expense of next-day sleepiness

Taking the nonhormonal dual neurokinin (NK) receptor antagonist elinzanetant (Lynkuet) at bedtime did not result in residual daytime sleepiness and actually improved sleepiness scores in postmenopausal women, according to a pooled post-hoc exploratory analysis of two phase III trials.

Participants taking elinzanetant had greater reductions in sleepiness scores across 12 weeks, particularly morning scores, reported Claudio Soares, MD, PhD, of Queen's University School of Medicine in Kingston, Ontario, Canada, during a presentation at the Menopause Societyopens in a new tab or window annual meeting, with mean changes from baseline to 12 weeks for elinzanetant versus placebo of:

• Total scores: -0.61 vs -0.46 (mean difference -0.15, unadjusted 95% CI -0.27 to -0.02)
• Morning scores: -0.66 vs -0.39 (mean difference -0.27, unadjusted 95% CI -0.42 to -0.13)
• Afternoon scores: -0.60 vs -0.45 (mean difference -0.15, unadjusted 95% CI -0.29 to -0.01)
• Evening scores: -0.56 vs -0.54 (mean difference -0.02, unadjusted 95% CI -0.16 to 0.12)

"Patients treated with this medication, hoping to improve their vasomotor symptoms and sleep problems, can be reassured that they are unlikely to experience sleepiness the next day as an undesired, residual effect," Soares told MedPage Today.

He and his colleagues noted in their presentation slides that "taken together, the findings suggest that elinzanetant does not induce next-day sleepiness and is therefore not expected to negatively impact next-day daytime functioning."

A previous phase I studyopens in a new tab or window also suggested that elinzanetant had no clinically relevant next-morning residual effect on simulated driving performance.

Of note, drugs that target sleep disturbance are taken in the evening, which runs the risk of increasing sleepiness and affecting functioning the following day. While elinzanetant is not indicated for sleep disturbance, it is recommended to be taken at bedtime.

In the OASIS I and OASIS IIopens in a new tab or window trials, elinzanetant, an NK1 and NK3 receptor antagonist, relieved the frequency and severity of hot flashes in postmenopausal women, and reduced sleep disturbance and improved menopause-related quality of life.

Based on these results, the FDA approvedopens in a new tab or window elinzanetant for the treatment of moderate to severe vasomotor symptoms due to menopause.

For this analysis, Soares and team used data from the OASIS I and II studies to assess the effects of elinzanetant on daytime sleepiness and evaluate whether bedtime dosing would have residual effects (i.e., sleepiness) the following day.

The researchers derived 7-day averages and calculated the mean change in the average total, morning, afternoon, and evening Sleepiness Scale scores (0 = not sleepy to 4 = very sleepy) from baseline to week 12. Mean baseline scores were 2.04 in the elinzanetant group and 1.94 in the placebo group.

The baseline mean T-score on the Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b (PROMIS SD-SF-8b) was 61.4 in the elinzanetant group and 60.5 in the placebo group, indicating moderate sleep disturbance. At the end of the placebo-controlled phase at week 12, the elinzanetant group had a reduction in score of 10.7 compared with a reduction of 5.3 in the placebo group (P<0.0001).

Data from the long-term OASIS-III trialopens in a new tab or window, showing similar trends of improved sleepiness, will be presented at a later date, Soares and colleagues said.