Efficacy and Safety of Fezolinetant in Moderate-to-Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT.
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BORIS DOI
Publisher DOI
PubMed ID
36734148
Description
CONTEXT
Vasomotor symptoms (VMS) are common, bothersome, and can persist for years before and after menopause.
OBJECTIVE
We aimed to assess efficacy/safety of fezolinetant for treatment of moderate-to-severe VMS associated with menopause.
METHODS
In this double-blind, placebo-controlled, 12-week (W) phase 3 trial with a 40W active treatment extension (NCT04003142; SKYLIGHT 2) women aged 40-65 years with minimum average 7 moderate-to-severe VMS/day were randomized to 12 weeks' once-daily placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Completers were rerandomized to fezolinetant 30/45 mg for 40 additional weeks. Coprimary efficacy endpoints were mean daily change from baseline to W4 and W12 in VMS frequency and severity. Safety was also assessed.
RESULTS
Both fezolinetant doses statistically significantly reduced VMS frequency/severity at W4 and W12 vs placebo. For VMS frequency, W4 least squares mean (SE) reduction vs placebo: fezolinetant 30 mg, -1.82 (0.46; P < .001); 45 mg, -2.55 (0.46; P < .001); W12: 30 mg, -1.86 (0.55; P < .001); 45 mg, -2.53 (0.55; P < .001). For VMS severity, W4: 30 mg, -0.15 (0.06; P<.05); 45 mg, -0.29 (0.06; P < .001); W12: 30 mg, -0.16 (0.08; P <.05); 45 mg, -0.29 (0.08; P < .001). Improvement in VMS frequency and severity was observed by W1; maintained through W52. Serious TEAEs were infrequent; these were reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively.
CONCLUSIONS
Daily fezolinetant 30 mg and 45 mg were efficacious and well-tolerated for treating moderate-to-severe VMS associated with menopause.
Vasomotor symptoms (VMS) are common, bothersome, and can persist for years before and after menopause.
OBJECTIVE
We aimed to assess efficacy/safety of fezolinetant for treatment of moderate-to-severe VMS associated with menopause.
METHODS
In this double-blind, placebo-controlled, 12-week (W) phase 3 trial with a 40W active treatment extension (NCT04003142; SKYLIGHT 2) women aged 40-65 years with minimum average 7 moderate-to-severe VMS/day were randomized to 12 weeks' once-daily placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Completers were rerandomized to fezolinetant 30/45 mg for 40 additional weeks. Coprimary efficacy endpoints were mean daily change from baseline to W4 and W12 in VMS frequency and severity. Safety was also assessed.
RESULTS
Both fezolinetant doses statistically significantly reduced VMS frequency/severity at W4 and W12 vs placebo. For VMS frequency, W4 least squares mean (SE) reduction vs placebo: fezolinetant 30 mg, -1.82 (0.46; P < .001); 45 mg, -2.55 (0.46; P < .001); W12: 30 mg, -1.86 (0.55; P < .001); 45 mg, -2.53 (0.55; P < .001). For VMS severity, W4: 30 mg, -0.15 (0.06; P<.05); 45 mg, -0.29 (0.06; P < .001); W12: 30 mg, -0.16 (0.08; P <.05); 45 mg, -0.29 (0.08; P < .001). Improvement in VMS frequency and severity was observed by W1; maintained through W52. Serious TEAEs were infrequent; these were reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively.
CONCLUSIONS
Daily fezolinetant 30 mg and 45 mg were efficacious and well-tolerated for treating moderate-to-severe VMS associated with menopause.
Date of Publication
2023-07-14
Publication Type
Article
Subject(s)
600 - Technology::610 - Medicine & health
Keyword(s)
KNDy fezolinetant neurokinin 3 receptor antagonist nonhormonal vasomotor symptoms
Language(s)
en
Contributor(s)
Johnson, Kimball A | |
Martin, Nancy | |
Nappi, Rossella E | |
Neal-Perry, Genevieve | |
Shapiro, Marla | |
Thurston, Rebecca C | |
Wolfman, Wendy | |
English, Marci | |
Franklin, Catherine | |
Lee, Misun | |
Santoro, Nanette |
Additional Credits
Universitätsklinik für Frauenheilkunde
Series
The Journal of clinical endocrinology and metabolism
Publisher
The Endocrine Society
ISSN
1945-7197
Access(Rights)
open.access