Title: Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomized, double-blind, placebo-controlled trial

Prauge JK, et al.


What You Need to Know:

MLE4901, a neurokinin 3 receptor antagonist, was safe and effective in the relief of menopausal hot flush symptoms without requiring estrogen in women.

Trial Design:

  • Phase 2, randomized, double-blind, placebo-controlled, single-center, cross over study
  • Healthy women aged 40-62 years with ≥7 hot flushes every 24 hours (some reported as severe or bothersome) who had no menstrual period for ≥12 month and who had not been taking any medication to improve flushes in the past 8 weeks were included
  • Study patients (n=37) were randomized to MLE4901 40mg twice daily or placebo twice daily separated by a 2-week washout
  • Primary outcome was total number of hot flushes during the final week of both treatment periods

Key Outcomes:

  • Of the 37 total patients randomized, 28 completed the trial
  • MLE4901 significantly reduced the total weekly number of hot flushes by 45 percentage points (95% CI: 22–67) vs. placebo (adjusted means [placebo] 49.01, 95% CI: 40.81–58.56 vs. [MLE4901] 19.35, 95% CI: 15.99–23.42)
  • The adjusted estimate of difference was 29.66 (95% CI: 17.39–42.87); P<0.0001)
  • Three patient developed elevated transaminase with normal bilirubin 28 days after starting MLE4910 treatment; levels normalized within 90 days
  • Adverse events: similar proportion between CSL830 and placebo; most common was mild and transient local site reactions
  • Bigger studies with longer time periods are needed