No Daytime Grogginess Observed With Menopause Hot Flash Drug

TL;DR

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A pooled post-hoc analysis of two phase III trials found that postmenopausal women taking bedtime elinzanetant had slightly greater reductions in reported daytime sleepiness than those taking placebo over 12 weeks. The exploratory findings do not establish that the drug improves alertness or rule out sleepiness in every patient.

A pooled, post-hoc analysis of two phase III trials found no increase in reported daytime sleepiness among postmenopausal women taking bedtime elinzanetant, compared with placebo, over 12 weeks. The analysis, presented by Claudio Soares of Queen’s University School of Medicine at the Menopause Society annual meeting, addresses a potential concern for patients taking an evening medication for menopause-related symptoms.

Researchers analyzed data from the OASIS I and OASIS II trials to examine whether taking elinzanetant at bedtime was followed by sleepiness during the next day. The drug is a nonhormonal neurokinin receptor antagonist approved by the FDA to treat moderate to severe vasomotor symptoms associated with menopause. Although it is taken at bedtime, it is not indicated as a treatment for sleep disturbance.

Participants’ sleepiness was assessed using a scale from 0, “not sleepy,” to 4, “very sleepy.” Researchers calculated average total and time-of-day scores from seven days of reports, comparing changes from baseline to week 12. Mean total scores fell by 0.61 points with elinzanetant and 0.46 with placebo, a mean difference of 0.15 points in favor of elinzanetant (unadjusted 95% confidence interval, 0.27 to 0.02 points lower).

The largest difference was in morning scores: they fell by 0.66 points in the elinzanetant group and 0.39 points in the placebo group, a mean difference of 0.27 points lower. Afternoon scores fell by 0.60 and 0.45 points, respectively. Evening scores changed by 0.56 points with elinzanetant and 0.54 with placebo, a difference of 0.02 points. The researchers described the analysis as exploratory; the reported confidence intervals were unadjusted.

What the Sleepiness Findings Mean

Sleep-related benefits can be a consideration when treating menopause symptoms, but a medicine taken at night may raise questions about alertness the following day. These results offer some reassurance that, on average, participants in the two trials did not report greater daytime sleepiness with elinzanetant than with placebo. The morning-score difference is particularly relevant to that concern, though it does not prove that every patient will feel alert after taking the drug.

The results also need to be read in proportion to the study design and measured outcomes. This was a post-hoc analysis, not a trial designed primarily to establish effects on daytime functioning. The average differences were modest, and the score changes do not by themselves show how participants performed at work, while driving, or during other daily activities. The findings concern reported sleepiness, not a broad guarantee about safety or function for an individual patient.

How the OASIS Trials Fit

OASIS I and OASIS II evaluated elinzanetant in postmenopausal women experiencing vasomotor symptoms, including hot flashes. According to the source report, the trials found reductions in hot-flash frequency and severity, as well as improvements in sleep disturbance and menopause-related quality of life. Those broader results formed the basis for the drug’s FDA approval for moderate to severe vasomotor symptoms due to menopause.

At baseline in the sleepiness analysis, the average sleepiness score was 2.04 in the elinzanetant group and 1.94 in the placebo group. Participants also reported moderate sleep disturbance on the PROMIS Sleep Disturbance Short Form 8b, with mean baseline T-scores of 61.4 and 60.5, respectively. By week 12, scores on that sleep-disturbance measure had fallen by 10.7 points with elinzanetant and 5.3 points with placebo; the reported comparison had P<0.0001. These sleep-disturbance findings are distinct from the daytime-sleepiness measure.

The report also cites an earlier phase I study that found no clinically relevant next-morning residual effect on simulated driving performance. That study provides related background, but it is separate evidence and does not replace assessment of driving or other functions in the phase III analysis.

“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.”

— Claudio Soares, MD, PhD, of Queen’s University School of Medicine, speaking to MedPage Today

Limits of the Sleepiness Analysis

The analysis was post hoc and exploratory, and the source report does not provide the number of participants included in this specific pooled assessment or details about how missing sleepiness reports were handled. It also does not establish whether the observed differences are meaningful in everyday life or whether they persist beyond the 12-week comparison.

The findings are averages and cannot rule out sleepiness for particular patients. They do not establish that elinzanetant improves alertness, nor do they prove that the medicine has no effect on every aspect of next-day functioning. The report describes the confidence intervals as unadjusted, and does not provide adjusted estimates for these sleepiness comparisons. The drug’s approved use is for vasomotor symptoms, not sleep disturbance.

Longer-Term OASIS Data Ahead

Soares and colleagues said data from the long-term OASIS III trial, which they described as showing similar trends in sleepiness, will be presented at a later date. The timing and full results were not specified in the report. Those data may add information about whether the pattern continues with longer follow-up, but the current analysis remains a 12-week comparison from OASIS I and II.

For now, the meeting presentation adds evidence about reported daytime sleepiness to the wider trial results on hot flashes and sleep disturbance. Further interpretation will depend on the later OASIS III presentation and on the details available about the analysis and its participants.

Key Questions

What did the analysis find about next-day sleepiness?

Over 12 weeks, average reported sleepiness scores fell slightly more with bedtime elinzanetant than with placebo. The researchers said the results suggest the medicine did not cause increased next-day sleepiness in the trial data.

Was elinzanetant studied as a sleep medicine?

No. The source report says elinzanetant is approved to treat moderate to severe menopause-related vasomotor symptoms, not sleep disturbance. The analysis examined sleepiness and sleep-related outcomes using data from trials of the medicine.

How large were the differences in sleepiness scores?

The mean total score decreased by 0.61 points with elinzanetant and 0.46 with placebo. Morning scores decreased by 0.66 and 0.39 points, respectively. These are average changes on a 0-to-4 scale and do not predict an individual patient’s experience.

Does the study prove that no patient will feel sleepy?

No. The findings are group averages from a post-hoc exploratory analysis. They do not rule out sleepiness or other effects in individual patients, and they are not a general guarantee about next-day functioning.

What additional evidence is expected?

The researchers said long-term OASIS III data showing similar sleepiness trends will be presented later. The report did not give a presentation date or additional results.

Source: rss