Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
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
_version_ 1785073672977907712
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
work_keys_str_mv AT johnsonkimballa efficacyandsafetyoffezolinetantinmoderatetoseverevasomotorsymptomsassociatedwithmenopauseaphase3rct
AT martinnancy efficacyandsafetyoffezolinetantinmoderatetoseverevasomotorsymptomsassociatedwithmenopauseaphase3rct
AT nappirossellae efficacyandsafetyoffezolinetantinmoderatetoseverevasomotorsymptomsassociatedwithmenopauseaphase3rct
AT nealperrygenevieve efficacyandsafetyoffezolinetantinmoderatetoseverevasomotorsymptomsassociatedwithmenopauseaphase3rct
AT shapiromarla efficacyandsafetyoffezolinetantinmoderatetoseverevasomotorsymptomsassociatedwithmenopauseaphase3rct
AT stutepetra efficacyandsafetyoffezolinetantinmoderatetoseverevasomotorsymptomsassociatedwithmenopauseaphase3rct
AT thurstonrebeccac efficacyandsafetyoffezolinetantinmoderatetoseverevasomotorsymptomsassociatedwithmenopauseaphase3rct
AT wolfmanwendy efficacyandsafetyoffezolinetantinmoderatetoseverevasomotorsymptomsassociatedwithmenopauseaphase3rct
AT englishmarci efficacyandsafetyoffezolinetantinmoderatetoseverevasomotorsymptomsassociatedwithmenopauseaphase3rct
AT franklincatherine efficacyandsafetyoffezolinetantinmoderatetoseverevasomotorsymptomsassociatedwithmenopauseaphase3rct
AT leemisun efficacyandsafetyoffezolinetantinmoderatetoseverevasomotorsymptomsassociatedwithmenopauseaphase3rct
AT santoronanette efficacyandsafetyoffezolinetantinmoderatetoseverevasomotorsymptomsassociatedwithmenopauseaphase3rct