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Relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial
BACKGROUND: Uterine leiomyomas are the most common neoplasm affecting women and frequently cause heavy menstrual bleeding and pain. Gonadotropin-releasing hormone (GnRH) receptor antagonists provide fast symptom relief and show promise as a medical (non-surgical) treatment option and as a presurgica...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555132/ https://www.ncbi.nlm.nih.gov/pubmed/34711224 http://dx.doi.org/10.1186/s12905-021-01475-2 |
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author | Hoshiai, Hiroshi Seki, Yoshifumi Kusumoto, Takeru Kudou, Kentarou Tanimoto, Masataka |
author_facet | Hoshiai, Hiroshi Seki, Yoshifumi Kusumoto, Takeru Kudou, Kentarou Tanimoto, Masataka |
author_sort | Hoshiai, Hiroshi |
collection | PubMed |
description | BACKGROUND: Uterine leiomyomas are the most common neoplasm affecting women and frequently cause heavy menstrual bleeding and pain. Gonadotropin-releasing hormone (GnRH) receptor antagonists provide fast symptom relief and show promise as a medical (non-surgical) treatment option and as a presurgical treatment to reduce leiomyoma size. The aim of this study was to evaluate the efficacy and safety of three dose levels of oral relugolix, a small molecule GnRH receptor antagonist, in Japanese women with uterine leiomyomas and heavy menstrual bleeding. METHODS: This phase 2, multicenter, double-blind, parallel-group study was conducted at 36 sites in Japan in women with uterine leiomyomas and heavy menstrual bleeding, defined as a pictorial blood loss assessment chart (PBAC) score of ≥ 120 in one menstrual cycle. Patients were randomized 1:1:1:1 to relugolix 10, 20, or 40 mg, or placebo, orally once daily for 12 weeks. The primary endpoint was the proportion of patients with a total PBAC score of < 10 from week 6 to 12. A sample size of 50 patients per group was estimated to provide ≥ 95% power, based on the comparison of relugolix 40 mg with placebo using a chi-square test with a significance level of 5% (two-sided). RESULTS: From November 2011 to September 2012, 216 patients were randomized and 214 patients (99.1%) were analyzed. The proportion (difference vs. placebo) of patients that achieved the primary endpoint in the placebo and 10-, 20-, and 40-mg relugolix groups were 0%, 20.8% (95% confidence interval [CI]: 9.3–32.3, P < .001), 42.6% (95% CI: 29.4–55.8, P < .001), and 83.3% (95% CI: 73.4–93.3, P < .001), respectively. Though treatment-emergent adverse events were similar between the 20- and 40-mg groups, the incidence rates were more frequent compared with the placebo group. Most of these adverse events were mild or moderate in intensity. CONCLUSIONS: Relugolix decreased menstrual blood loss in women with uterine leiomyomas in a dose–response manner, and was generally well tolerated. Clinical trial registration: ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01452659, NCT01452659 (registered 17/10/2011); JAPIC Clinical Trial Information, https://www.clinicaltrials.jp, JapicCTI-111590 (registered 31/08/2011). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12905-021-01475-2. |
format | Online Article Text |
id | pubmed-8555132 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-85551322021-10-29 Relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial Hoshiai, Hiroshi Seki, Yoshifumi Kusumoto, Takeru Kudou, Kentarou Tanimoto, Masataka BMC Womens Health Research BACKGROUND: Uterine leiomyomas are the most common neoplasm affecting women and frequently cause heavy menstrual bleeding and pain. Gonadotropin-releasing hormone (GnRH) receptor antagonists provide fast symptom relief and show promise as a medical (non-surgical) treatment option and as a presurgical treatment to reduce leiomyoma size. The aim of this study was to evaluate the efficacy and safety of three dose levels of oral relugolix, a small molecule GnRH receptor antagonist, in Japanese women with uterine leiomyomas and heavy menstrual bleeding. METHODS: This phase 2, multicenter, double-blind, parallel-group study was conducted at 36 sites in Japan in women with uterine leiomyomas and heavy menstrual bleeding, defined as a pictorial blood loss assessment chart (PBAC) score of ≥ 120 in one menstrual cycle. Patients were randomized 1:1:1:1 to relugolix 10, 20, or 40 mg, or placebo, orally once daily for 12 weeks. The primary endpoint was the proportion of patients with a total PBAC score of < 10 from week 6 to 12. A sample size of 50 patients per group was estimated to provide ≥ 95% power, based on the comparison of relugolix 40 mg with placebo using a chi-square test with a significance level of 5% (two-sided). RESULTS: From November 2011 to September 2012, 216 patients were randomized and 214 patients (99.1%) were analyzed. The proportion (difference vs. placebo) of patients that achieved the primary endpoint in the placebo and 10-, 20-, and 40-mg relugolix groups were 0%, 20.8% (95% confidence interval [CI]: 9.3–32.3, P < .001), 42.6% (95% CI: 29.4–55.8, P < .001), and 83.3% (95% CI: 73.4–93.3, P < .001), respectively. Though treatment-emergent adverse events were similar between the 20- and 40-mg groups, the incidence rates were more frequent compared with the placebo group. Most of these adverse events were mild or moderate in intensity. CONCLUSIONS: Relugolix decreased menstrual blood loss in women with uterine leiomyomas in a dose–response manner, and was generally well tolerated. Clinical trial registration: ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01452659, NCT01452659 (registered 17/10/2011); JAPIC Clinical Trial Information, https://www.clinicaltrials.jp, JapicCTI-111590 (registered 31/08/2011). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12905-021-01475-2. BioMed Central 2021-10-28 /pmc/articles/PMC8555132/ /pubmed/34711224 http://dx.doi.org/10.1186/s12905-021-01475-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Hoshiai, Hiroshi Seki, Yoshifumi Kusumoto, Takeru Kudou, Kentarou Tanimoto, Masataka Relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial |
title | Relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial |
title_full | Relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial |
title_fullStr | Relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial |
title_full_unstemmed | Relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial |
title_short | Relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial |
title_sort | relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555132/ https://www.ncbi.nlm.nih.gov/pubmed/34711224 http://dx.doi.org/10.1186/s12905-021-01475-2 |
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