Abstract
Context
The thermoregulatory center in the hypothalamus is stimulated by neurokinin 3 receptor (NK3R) activation and inhibited by estrogen-negative feedback. This balance is disrupted in menopause, producing vasomotor symptoms (VMSs).
Objective
To evaluate safety and efficacy of the NK3R antagonist fezolinetant in menopausal VMSs.
Design
Twelve-week, double-blind, randomized, placebo-controlled study.
Setting
Eight Belgian centers from September 2015 to October 2016.
Participants
Generally healthy menopausal women aged 40 to 65 years with moderate/severe VMSs.
Interventions
Subjects were randomized (1:1) to 90 mg of fezolinetant twice daily or placebo for 12 weeks.
Main Outcome Measures
Subjects captured VMS severity and frequency using an electronic diary. The primary outcome was change from baseline to week 12 in total VMS score with fezolinetant vs placebo. Secondary outcomes included timing of changes in frequency and severity of moderate/severe VMSs and quality-of-life assessments at weeks 4, 8, and 12. Pharmacodynamic and pharmacokinetic effects were assessed, as were safety and tolerability.
Results
Of 122 subjects screened, 87 were randomized and 80 (92%) completed the study. At week 12, fezolinetant significantly reduced total VMS score vs placebo (−26.5 vs −12.2, P < 0.001) and decreased mean frequency of moderate/severe VMSs by five episodes per day vs placebo. Severity and frequency of moderate/severe VMSs were reduced from the first day of treatment. Improvements were achieved in all quality-of-life measures. Fezolinetant was well tolerated. The most common fezolinetant-related adverse event was gastrointestinal disorder (n = 6).
Conclusions
Fezolinetant rapidly and significantly reduced moderate/severe VMSs, supporting its potential as an effective nonhormonal treatment option for menopausal women.
Effect of the neurokinin 3 receptor antagonist fezolinetant on patient-reported outcomes in postmenopausal women with vasomotor symptoms: results of a randomized, placebo-controlled, double-blind, dose-ranging study (VESTA)