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.
RCT Entities:
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.
Authors: Richard A Anderson; Jennifer Cormier; Ruth Thieroff-Ekerdt; Malcolm Boyce; Frans van den Berg; Daniel Grau; David Turnquist; Deya Corzo; Philip Graham Journal: J Clin Endocrinol Metab Date: 2020-12-01 Impact factor: 5.958
Authors: Stephanie S Faubion; Amanda King; Andrea G Kattah; Carol L Kuhle; Richa Sood; Juliana M Kling; Kristin C Mara; Ekta Kapoor Journal: Menopause Date: 2020-08-17 Impact factor: 3.310
Authors: Graeme L Fraser; Samuel Lederman; Arthur Waldbaum; Robin Kroll; Nanette Santoro; Misun Lee; Laurence Skillern; Steven Ramael Journal: Menopause Date: 2020-04 Impact factor: 3.310
Authors: Nanette Santoro; Arthur Waldbaum; Samuel Lederman; Robin Kroll; Graeme L Fraser; Christopher Lademacher; Laurence Skillern; James Young; Steven Ramael Journal: Menopause Date: 2020-12 Impact factor: 3.310