NCT02655224

A Placebo-Controlled, Phase 3 Study of Relugolix (TAK-385) 40 mg in the Treatment of Pain Symptoms Associated With Uterine Fibroids

Completed Phase 3 Results posted Last updated 22 March 2019

What this trial tests

Phase 3 trial testing Relugolix in Uterine Fibroids in 65 participants. Completed in 19 May 2017.

Timeline

26 March 2016

Primary endpoint
16 May 2017

19 May 2017

Quick facts

Lead sponsor	Takeda
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	65
Start date	26 March 2016
Primary completion	16 May 2017
Estimated completion	19 May 2017
Sites	11 locations across Japan

Drugs / interventions tested

• Relugolix (relugolix) — full drug profile →
• Relugolix placebo

Conditions studied

• Uterine Fibroids — all drugs for Uterine Fibroids →

Sponsor

Takeda — full company profile →

Who can join

20 and older, female only, with Uterine Fibroids. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With a Maximum NRS Score of 1 or Less During the 28 Days Before the Final Dose of Study Drug Primary · For 28 days before the final dose of study drug (up to Week 12)

Pain symptoms were evaluated using the NRS score. NRS score is a self-reported instrument assessing pain from 0 to 10. Higher scores reflect greater level of pain. The percentage of participants with a score of 1 or less is reported.

Group	Value	95% CI
Relugolix 40 mg	57.6
Placebo	3.1

Percentage of Participants With a Maximum NRS Score of 0 During the 28 Days Before the Final Dose of Study Drug Secondary · For 28 days before the final dose of study drug (up to Week 12)

Pain symptoms were evaluated using the NRS score. NRS score is a self-reported instrument assessing pain from 0 to 10. Higher scores reflect greater level of pain. The percentage of participants with a score of 0 is reported.

Group	Value	95% CI
Relugolix 40 mg	48.5
Placebo	3.1

Mean NRS Score During the 28 Days Before the Final Dose of Study Drug Secondary · For 28 days before the final dose of study drug (up to Week 12)

Pain symptoms were evaluated using the NRS score. NRS score is a self-reported instrument assessing pain from 0 to 10. Higher scores reflect greater level of pain.

Group	Value	95% CI
Relugolix 40 mg	0.50	± 0.967
Placebo	0.99	± 1.274

Percentage of Days Without Pain Symptoms (NRS = 0) During the 28 Days Before the Final Dose of Study Drug Secondary · For 28 days before the final dose of study drug (up to Week 12)

Percentage of day without pain symptoms (NRS = 0) was reported. Number of days without pain symptoms is determined by a zero score on the NRS. Pain symptoms were evaluated using the NRS score. NRS score is a self-reported instrument assessing pain from 0 to 10. Higher scores reflect greater level of pain. Percentage of days without pain symptoms (NRS=0) during the 28 days before the final dose of study drug (%) = \[(number of days without pain symptoms (NRS=0) during the last 28 days of the treatment)/(number of days with available data during the last 28 days of the treatment)\]\*100.

Group	Value	95% CI
Relugolix 40 mg	76.73	± 32.006
Placebo	64.78	± 29.015

Percentage of Participants With Maximum NRS Score of 1 or Less From Day 1 to 28, From Day 29 to 56, and From Day 57 to 84 Secondary · Day 1 to 28, Day 29 to 56, and Day 57 to 84

Pain symptoms were evaluated using the NRS score. NRS score is a self-reported instrument assessing pain from 0 to 10. Higher scores reflect greater level of pain. The percentage of participants with a score of 1 or less is reported.

Day 1 to 28

Group	Value	95% CI
Relugolix 40 mg	24.2
Placebo	0.0

Day 29 to 56

Group	Value	95% CI
Relugolix 40 mg	45.5
Placebo	12.9

Day 57 to 84

Group	Value	95% CI
Relugolix 40 mg	59.4
Placebo	12.9

Percentage of Participants With a Maximum NRS Score of 0 From Day 1 to 28, From Day 29 to 56, and From Day 57 to 84 Secondary · Day 1 to 28, Day 29 to 56, and Day 57 to 84

Pain symptoms were evaluated using the NRS score. NRS score is a self-reported instrument assessing pain from 0 to 10. Higher scores reflect greater level of pain. The percentage of participants with a score of 0 is reported.

Day 1 to 28

Group	Value	95% CI
Relugolix 40 mg	15.2
Placebo	0.0

Day 29 to 56

Group	Value	95% CI
Relugolix 40 mg	27.3
Placebo	6.5

Day 57 to 84

Group	Value	95% CI
Relugolix 40 mg	46.9
Placebo	6.5

Mean NRS Score From Day 1 to 28, From Day 29 to 56, and From Day 57 to 84 Secondary · Day 1 to 28, Day 29 to 56, and Day 57 to 84

Pain symptoms were evaluated using the NRS score. NRS score is a self-reported instrument assessing pain from 0 to 10. Higher scores reflect greater level of pain.

Day 1 to 28

Group	Value	95% CI
Relugolix 40 mg	1.26	± 1.490
Placebo	1.17	± 1.141

Day 29 to 56

Group	Value	95% CI
Relugolix 40 mg	0.59	± 0.991
Placebo	1.16	± 1.457

Day 57 to 84

Group	Value	95% CI
Relugolix 40 mg	0.43	± 0.776
Placebo	0.97	± 1.279

Percentage of Days Without Pain Symptoms (NRS = 0) From Day 1 to 28, From Day 29 to 56, and From Day 57 to 84 Secondary · Day 1 to 28, Day 29 to 56, and Day 57 to 84

Percentage of day without pain symptoms (NRS = 0) was reported. Number of days without pain symptoms is determined by a zero score on the NRS. Pain symptoms were evaluated using the NRS score. NRS score is a self-reported instrument assessing pain from 0 to 10. Higher scores reflect greater level of pain. Percentage of days without pain symptoms (NRS=0) (%) = \[(number of days without pain symptoms (NRS=0) during the last 28 days of the treatment)/(number of days with available data during the last 28 days of the treatment)\]\*100.

Day 1 to 28

Group	Value	95% CI
Relugolix 40 mg	60.49	± 34.043
Placebo	56.32	± 28.891

Day 29 to 56

Group	Value	95% CI
Relugolix 40 mg	73.98	± 31.718
Placebo	61.29	± 31.459

Day 57 to 84

Group	Value	95% CI
Relugolix 40 mg	77.43	± 30.854
Placebo	65.84	± 29.224

Number of Participants Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE) Secondary · Up to Week 16

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

Group	Value	95% CI
Relugolix 40 mg	29
Placebo	18

Number of Participants With Markedly Abnormal Values of Vital Signs Secondary · Up to Week 16

Vital signs included sitting blood pressure (after the participant has rested for at least 5 minutes), body temperature (oral or tympanic measurement) (degree Celsius \[°C\]) and pulse (beats per minute \[bpm\]) are reported.

Diastolic Blood Pressure Lower (<50 mmHg)

Group	Value	95% CI
Relugolix 40 mg	2
Placebo	1

Body temperature Lower (<35.6 °C)

Group	Value	95% CI
Relugolix 40 mg	4
Placebo	2

Number of Participants With TEAEs Related to Weight Secondary · Up to Week 16

Number of participants with TEAEs of which threshold was 5% or above in either treatment group related to weight was reported.

Group	Value	95% CI
Relugolix 40 mg	0
Placebo	0

Number of Participants With TEAEs Related to Standard 12-lead Electrocardiogram (ECG) Secondary · Up to Week 16

Number of participants with TEAEs of which threshold was 5% or above in either treatment group related to ECG was reported.

Group	Value	95% CI
Relugolix 40 mg	0
Placebo	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Week 16. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Relugolix 40 mg

Serious: 0/33 (0%)

Deaths: 0/33

Placebo

Serious: 0/32 (0%)

Deaths: 0/32

Other adverse events (13 terms — click to expand)

Reaction	System	Relugolix 40 mg	Placebo
Hot flush	Vascular disorders	—	—
Metrorrhagia	Reproductive system and breast disorders	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—
Hyperhidrosis	Skin and subcutaneous tissue disorders	—	—
Menorrhagia	Reproductive system and breast disorders	—	—
Insomnia	Psychiatric disorders	—	—
Menstruation irregular	Reproductive system and breast disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Headache	Nervous system disorders	—	—
Genital haemorrhage	Reproductive system and breast disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—

Data from ClinicalTrials.gov NCT02655224 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the efficacy and safety of Relugolix (TAK-385) in patients having pain symptoms associated with uterine fibroids.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Relugolix, a novel oral gonadotropin-releasing hormone antagonist, in the treatment of pain symptoms associated with uterine fibroids: a randomized, placebo-controlled, phase 3 study in Japanese women.
   Osuga Y, Enya K, Kudou K, Hoshiai H. · · 2019 · cited 52× · PMID 31594635 · DOI 10.1016/j.fertnstert.2019.07.013