Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, in women with endometriosis-associated pain: phase 2 safety and efficacy 24-week results.

Osuga Y, Seki Y, Tanimoto M, Kusumoto T, Kudou K, Terakawa N

BMC women's health21 Jun 2021Cited by 33 (Europe PMC)

PMID34154590PMCIDPMC8218467DOI10.1186/s12905-021-01393-3PepBankPUB-34154590

Summary

BackgroundRelugolix is a once-daily, oral, nonpeptide, gonadotropin-releasing hormone receptor antagonist. The aim of this study was to evaluate safety of relugolix over 24 weeks in women with endometriosis-associated pain.MethodsThis phase 2, randomized, open-label, parallel-group extension study was conducted in 101 clinics in Japan. Patients (premenopausal females ≥ 20 years) who completed the preceding 12-week relugolix phase 2 study continued to receive relugolix (10 mg, 20 mg, or 40 mg), placebo, or leuprorelin (3.75 mg) for an additional 12 weeks. Relugolix was administered orally once daily, and leuprorelin subcutaneously once every 4 weeks. The primary outcome was safety, including bone mineral density (BMD) and treatment-emergent adverse events (TEAEs). Secondary endpoints included visual analog scale (VAS) scores for endometriosis-associated pain. Analysis sets were defined as all patients who were administered the study drug.ResultsOf 487 randomized patients in the preceding study, 397 enrolled in this extension study and continued to receive placebo (n = 77), relugolix 10 mg (n = 84), relugolix 20 mg (n = 78), relugolix 40 mg (n = 89), or leuprorelin (n = 69). Baseline characteristics were similar between extension study patients and patients in the preceding study. Frequency of TEAEs including metrorrhagia, menorrhagia, and hot flush was similar in the relugolix 40-mg and leuprorelin groups. Mean (SD) change in BMD from baseline at Week 24 was - 0.2 (1.99)% for placebo; - 1.6 (2.34)%, - 2.6 (2.94)%, and - 4.9 (2.91)% for the relugolix 10-mg, 20-mg, and 40-mg groups, respectively; and - 4.4 (2.16)% for leuprorelin. Mean ± SD change from baseline in mean VAS score (mm) for pelvic pain at end of treatment was - 3.2 ± 12.16 for placebo; - 6.8 ± 10.56, - 9.0 ± 11.84, and - 11.9 ± 11.26 for the relugolix 10-mg, 20-mg, and 40-mg groups, respectively; and - 12.7 ± 12.57 for leuprorelin. Estradiol levels decreased with increasing relugolix dose and remained below postmenopausal levels throughout the 24-week relugolix 40-mg treatment period.ConclusionsTreatment with relugolix for 24 weeks was generally well tolerated and demonstrated similar pain reduction to leuprorelin in women with endometriosis. The dose-dependent loss in BMD observed with relugolix treatment was expected due to an induced hypoestrogenic state. Relugolix demonstrated a similar benefit/risk profile to injectable therapy in this phase 2 study. Trial registration NCT01452685 (ClinicalTrials.gov, registered 17/10/2011).

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

5 results from studies that gave the peptide. 5 results from people.

01HumanRandomized controlled trialSafety outcome
In women with endometriosis, metrorrhagia was included among treatment-emergent events with similar frequency during leuprorelin and relugolix 40-mg treatment.
In plain wordsIn women with endometriosis, metrorrhagia was among adverse events reported at similar frequency with leuprorelin and relugolix 40 mg.
Peptide
Leuprolide
Outcome
Direction not reportedMetrorrhagia
Study
n: not reported in source
Comparator
Relugolix 40 mg
Analysis
Primary
Outcome group
Adverse events · Reproductive and sexual health
Studied dose
3.75 mg every 4 weeks · subcutaneous · 24 weeksAs given in this study (human).
Source sentences
Summary
Frequency of TEAEs including metrorrhagia, menorrhagia, and hot flush was similar in the relugolix 40-mg and leuprorelin groups.
3 context sentences(design, population, supporting numbers)
Summary · context
This phase 2, randomized, open-label, parallel-group extension study was conducted in 101 clinics in Japan.
Summary · context
Patients (premenopausal females ≥ 20 years) who completed the preceding 12-week relugolix phase 2 study continued to receive relugolix (10 mg, 20 mg, or 40 mg), placebo, or leuprorelin (3.75 mg) for an additional 12 weeks.
Summary · context
Relugolix was administered orally once daily, and leuprorelin subcutaneously once every 4 weeks.
Show in the study text Report a problemFND-3415459001
02HumanRandomized controlled trialSafety outcome
In women with endometriosis, menorrhagia was included among treatment-emergent events with similar frequency during leuprorelin and relugolix 40-mg treatment.
In plain wordsIn women with endometriosis, menorrhagia was among adverse events reported at similar frequency with leuprorelin and relugolix 40 mg.
Peptide
Leuprolide
Outcome
Direction not reportedMenorrhagia
Study
n: not reported in source
Comparator
Relugolix 40 mg
Analysis
Primary
Outcome group
Adverse events · Reproductive and sexual health
Studied dose
3.75 mg every 4 weeks · subcutaneous · 24 weeksAs given in this study (human).
Source sentences
Summary
Frequency of TEAEs including metrorrhagia, menorrhagia, and hot flush was similar in the relugolix 40-mg and leuprorelin groups.
3 context sentences(design, population, supporting numbers)
Summary · context
This phase 2, randomized, open-label, parallel-group extension study was conducted in 101 clinics in Japan.
Summary · context
Patients (premenopausal females ≥ 20 years) who completed the preceding 12-week relugolix phase 2 study continued to receive relugolix (10 mg, 20 mg, or 40 mg), placebo, or leuprorelin (3.75 mg) for an additional 12 weeks.
Summary · context
Relugolix was administered orally once daily, and leuprorelin subcutaneously once every 4 weeks.
Show in the study text Report a problemFND-3415459002
03HumanRandomized controlled trialSafety outcome
In women with endometriosis, hot flush was included among treatment-emergent events with similar frequency during leuprorelin and relugolix 40-mg treatment.
In plain wordsIn women with endometriosis, hot flush was among adverse events reported at similar frequency with leuprorelin and relugolix 40 mg.
Peptide
Leuprolide
Outcome
Direction not reportedHot flush
Study
n: not reported in source
Comparator
Relugolix 40 mg
Analysis
Primary
Outcome group
Adverse events · Endocrine and hormones
Studied dose
3.75 mg every 4 weeks · subcutaneous · 24 weeksAs given in this study (human).
Source sentences
Summary
Frequency of TEAEs including metrorrhagia, menorrhagia, and hot flush was similar in the relugolix 40-mg and leuprorelin groups.
3 context sentences(design, population, supporting numbers)
Summary · context
This phase 2, randomized, open-label, parallel-group extension study was conducted in 101 clinics in Japan.
Summary · context
Patients (premenopausal females ≥ 20 years) who completed the preceding 12-week relugolix phase 2 study continued to receive relugolix (10 mg, 20 mg, or 40 mg), placebo, or leuprorelin (3.75 mg) for an additional 12 weeks.
Summary · context
Relugolix was administered orally once daily, and leuprorelin subcutaneously once every 4 weeks.
Show in the study text Report a problemFND-3415459003
04HumanNon-randomized trialSafety outcome
In women with endometriosis, leuprorelin reduced bone mineral density by a mean 4.4% at Week 24 (SD 2.16%).
In plain wordsIn women with endometriosis, bone mineral density fell by 4.4% with leuprorelin at Week 24.
Peptide
Leuprolide
Outcome
DecreaseBone mineral density change
Study
n = 69
Analysis
Primary
Outcome group
Bone and joint · Musculoskeletal
Studied dose
3.75 mg every 4 weeks · subcutaneous · 24 weeksAs given in this study (human).
Measurements
BMD change
−4.4%
Week 24
SD
2.16%
leuprorelin
Source sentences
Summary
Mean (SD) change in BMD from baseline at Week 24 was - 0.2 (1.99)% for placebo; - 1.6 (2.34)%, - 2.6 (2.94)%, and - 4.9 (2.91)% for the relugolix 10-mg, 20-mg, and 40-mg groups, respectively; and - 4.4 (2.16)% for leuprorelin.
3 context sentences(design, population, supporting numbers)
Summary · context
This phase 2, randomized, open-label, parallel-group extension study was conducted in 101 clinics in Japan.
Summary · context
Patients (premenopausal females ≥ 20 years) who completed the preceding 12-week relugolix phase 2 study continued to receive relugolix (10 mg, 20 mg, or 40 mg), placebo, or leuprorelin (3.75 mg) for an additional 12 weeks.
Summary · context
Relugolix was administered orally once daily, and leuprorelin subcutaneously once every 4 weeks.
Show in the study text Report a problemFND-3415459005
05HumanNon-randomized trialEfficacy outcome
In women with endometriosis, leuprorelin reduced mean pelvic pain VAS by 12.7 mm at treatment end (SD 12.57).
In plain wordsIn women with endometriosis, pelvic pain scores fell by 12.7 mm with leuprorelin.
Peptide
Leuprolide
Outcome
DecreasePelvic pain VAS change
Study
n = 69
Analysis
Secondary
Outcome group
Pain · Reproductive and sexual health
Studied dose
3.75 mg every 4 weeks · subcutaneous · 24 weeksAs given in this study (human).
Measurements
VAS change
−12.7 mm
end of treatment
SD
12.57 mm
leuprorelin
Source sentences
Summary
Mean ± SD change from baseline in mean VAS score (mm) for pelvic pain at end of treatment was - 3.2 ± 12.16 for placebo; - 6.8 ± 10.56, - 9.0 ± 11.84, and - 11.9 ± 11.26 for the relugolix 10-mg, 20-mg, and 40-mg groups, respectively; and - 12.7 ± 12.57 for leuprorelin.
3 context sentences(design, population, supporting numbers)
Summary · context
This phase 2, randomized, open-label, parallel-group extension study was conducted in 101 clinics in Japan.
Summary · context
Patients (premenopausal females ≥ 20 years) who completed the preceding 12-week relugolix phase 2 study continued to receive relugolix (10 mg, 20 mg, or 40 mg), placebo, or leuprorelin (3.75 mg) for an additional 12 weeks.
Summary · context
Relugolix was administered orally once daily, and leuprorelin subcutaneously once every 4 weeks.
Show in the study text Report a problemFND-3415459006

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2NCT01452685

A Long-term Extension Study of TAK-385 in the Treatment of Endometriosis

Takedan = 397Mar 2012 to Dec 2013

Endometriosis

Trial page ClinicalTrials.govUpdated 8 May 2014

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:37 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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