FIG. 1.

Summary of protocol: baseline period: participants underwent a 2-week period to gather baseline data on hot flush (HF) frequency, HF severity, HF bother, and perceived HF interference (Hot Flash-Related Daily Interference Scale). If the inclusion criteria regarding HF frequency and severity were met at the end of this period, then they were assigned to the active phase of the study after randomization (black circle). Intervention 1 (double-blind): all participants randomized to either 4 weeks of treatment with oral, 40 mg twice daily MLE4901 or exact-match placebo. Washout period: all participants underwent a 2-week washout period after intervention 1 (half-life of MLE4901 is 8.5 h). Intervention 2 (double-blind): all participants then switched to receive either four weeks treatment with oral twice daily exact-match placebo or oral 40 mg twice daily MLE4901 depending on which intervention they received first. Monitoring period: a subsequent 2-week period to complete safety monitoring. Figure available under the terms of the CC BY licence from http://dx.doi.org/10.1016/S0140-6736(17)30823-1 (Prague et al, Lancet, 2017¹⁸).