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Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348473/ https://www.ncbi.nlm.nih.gov/pubmed/36734148 http://dx.doi.org/10.1210/clinem/dgad058 |
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author | Johnson, Kimball A Martin, Nancy Nappi, Rossella E Neal-Perry, Genevieve Shapiro, Marla Stute, Petra Thurston, Rebecca C Wolfman, Wendy English, Marci Franklin, Catherine Lee, Misun Santoro, Nanette |
author_facet | Johnson, Kimball A Martin, Nancy Nappi, Rossella E Neal-Perry, Genevieve Shapiro, Marla Stute, Petra Thurston, Rebecca C Wolfman, Wendy English, Marci Franklin, Catherine Lee, Misun Santoro, Nanette |
author_sort | Johnson, Kimball A |
collection | PubMed |
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 phase 3 trial with a 40-week active treatment extension (NCT04003142; SKYLIGHT 2), women aged 40 to 65 years with minimum average 7 moderate to severe VMS/day were randomized to 12 weeks of 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 week 4 (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 and maintained through W52. Serious treatment-emergent adverse events were infrequent, reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively. CONCLUSION: Daily fezolinetant 30 and 45 mg were efficacious and well tolerated for treating moderate to severe VMS associated with menopause. |
format | Online Article Text |
id | pubmed-10348473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-103484732023-07-15 Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT Johnson, Kimball A Martin, Nancy Nappi, Rossella E Neal-Perry, Genevieve Shapiro, Marla Stute, Petra Thurston, Rebecca C Wolfman, Wendy English, Marci Franklin, Catherine Lee, Misun Santoro, Nanette J Clin Endocrinol Metab Clinical Research Article 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 phase 3 trial with a 40-week active treatment extension (NCT04003142; SKYLIGHT 2), women aged 40 to 65 years with minimum average 7 moderate to severe VMS/day were randomized to 12 weeks of 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 week 4 (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 and maintained through W52. Serious treatment-emergent adverse events were infrequent, reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively. CONCLUSION: Daily fezolinetant 30 and 45 mg were efficacious and well tolerated for treating moderate to severe VMS associated with menopause. Oxford University Press 2023-02-03 /pmc/articles/PMC10348473/ /pubmed/36734148 http://dx.doi.org/10.1210/clinem/dgad058 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Clinical Research Article Johnson, Kimball A Martin, Nancy Nappi, Rossella E Neal-Perry, Genevieve Shapiro, Marla Stute, Petra Thurston, Rebecca C Wolfman, Wendy English, Marci Franklin, Catherine Lee, Misun Santoro, Nanette Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT |
title | Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT |
title_full | Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT |
title_fullStr | Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT |
title_full_unstemmed | Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT |
title_short | Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT |
title_sort | efficacy and safety of fezolinetant in moderate to severe vasomotor symptoms associated with menopause: a phase 3 rct |
topic | Clinical Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348473/ https://www.ncbi.nlm.nih.gov/pubmed/36734148 http://dx.doi.org/10.1210/clinem/dgad058 |
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