A Phase 3 Study to Evaluate the Efficacy and Safety of Re... | NCT02655237

ID	Type	Description	Link
U1111-1178-0989	Registry Identifier	WHO
JapicCTI-163128	Registry Identifier	JapicCTI

Label	Type	Description	Intervention Names
Relugolix 40 mg	Experimental	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.	Drug: Relugolix Drug: Relugolix Placebo Drug: Leuprorelin Placebo
Leuprorelin 1.88 mg or 3.75 mg	Active Comparator	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.	Drug: Relugolix Placebo Drug: Leuprorelin Drug: Leuprorelin Placebo

Name	Type	Description	Arm Group Labels	Other Names
Relugolix	Drug	Relugolix tablets	Relugolix 40 mg	TAK-385

Measure	Description	Time Frame
Percentage of Participants With Total PBAC Score of <10 From Week 6 to 12	PBAC score was used to measure volume of menstrual blood loss. Participants used sanitary products designated by sponsor and recorded the numbers of tampons or towels used, clots and flooding in patient diary. Three diagrams used which represented a lightly, moderately stained or completely saturated pad/tampon. Following scores assigned: 1) 1, 5, or 20 points for each pad; 2) 1, 5, or 10 points for each tampon; 3) 1 or 5 points for each blood clot of <1 cm/=1 cm/>1 in longest diameter; 4) 5 points for each episode of flooding. The total PBAC score (sum of points) ranges from 0 to >500.	Week 6 to 12

Measure	Description	Time Frame
Percentage of Participants With Total PBAC Score of <10 From Week 2 to 6	PBAC score was used to measure volume of menstrual blood loss. Participants used sanitary products designated by sponsor and recorded the numbers of tampons or towels used, clots and flooding in patient diary. Three diagrams used which represented a lightly, moderately stained or completely saturated pad/tampon. Following scores assigned: 1) 1, 5, or 20 points for each pad; 2) 1, 5, or 10 points for each tampon; 3) 1 or 5 points for each blood clot of <1 cm/=1 cm/>1 in longest diameter; 4) 5 points for each episode of flooding. The total PBAC score (sum of points) ranges from 0 to >500.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Inclusion Criteria for Entering the Screening (at VISIT 1)

In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements.
The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.
Prior to VISIT 1, the participant has a diagnosis of uterine fibroids confirmed by transvaginal ultrasound, abdominal ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), or laparoscopy, and has never received any surgical treatment for the myoma (measurable noncalcified myoma with the longest diameter of ≥ 3 cm).
The participant is a premenopausal Japanese woman.
The participant is aged 20 years or older on the day of signing and dating the informed consent form.
The participant has 1 or more measurable noncalcified myomas with the longest diameter of ≥ 3 cm confirmed by transvaginal ultrasound.
The participant has experienced 1 or more regular menstrual cycles (25 to 38 days) immediately prior to VISIT 1 and that should include menstrual bleeding for at least 3 consecutive days.
The participant who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the study.

Inclusion Criteria for Entering the Run-in (at VISIT 2)
The participant has experienced regular menstrual cycles (25 to 38 days) immediately prior to VISIT 2 that should include menstrual bleeding of at least 3 consecutive days (at least 2 regular menstruation cycles to be confirmed by Inclusion criteria #7 and #9).

Inclusion Criteria for Entering the Treatment (at VISIT 3)
The participant has 1 or more measurable noncalcified myomas, with a longest diameter of ≥ 3 cm confirmed by transvaginal ultrasound (the same myoma should be measured as in Inclusion criterion #6).
The participant has a diagnosis of menorrhagia with a total Pictorial Blood loss Assessment Chart (PBAC) score of ≥ 120 in 1 menstrual cycle just before VISIT 3.
The participant has experienced regular menstrual cycles (25 to 38 days) after VISIT 1 that should include menstrual bleeding for at least 3 consecutive days (at least 3 regular menstruation cycles to be confirmed by Inclusion criteria #7, #9 and #12).

Exclusion Criteria:

The participant has received any investigational compound within 24 weeks prior to the start of the administration of the study medication for the Run-in (VISIT 2).
The participant has received relugolix (including placebo) in a previous clinical study.
The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
The participant has a previous or current history of blood disorders (eg, thalassemia, sickle cells anemia, folic-acid deficiency, and coagulopathy), excluding (latent) iron-deficiency anemia.
The participant has a known history of severe hypersensitivity or severe allergy to sanitary goods.
The participant has lower abdominal pain due to irritable bowel syndrome or severe interstitial cystitis.
The participant has a current history of thyroid gland disorder with irregular menstruation, or has a potential for irregular menstruation due to thyroid gland disorder, as determined by the investigator or subinvestigator.
The participant has a previous or current history of pelvic inflammatory disease within 8 weeks prior to VISIT 1.
The participant has a positive Pap smear test result obtained within 1 year prior to VISIT 1 (if there are no previous test results, those who were judged positive in the test conducted before VISIT 2).
The participant has a history of panhysterectomy or bilateral oophorectomy.
The participant has had markedly abnormal uterine bleeding or anovulatory bleeding, as determined by the investigator or subinvestigator.
The participant has a malignant tumor or a history of a malignant tumor within 5 years prior to VISIT 1.
The participant has been treated with any of the following drugs (excluding drugs for external use and dietary supplements) within 4 weeks prior to VISIT 2: anti-coagulant drugs, anti-platelet drugs, tranexamic acid, selective estrogen receptor modulators (SERMs), activated vitamin D preparations, other vitamin D preparations, calcitonin, ipriflavone, steroid hormones, vitamin K preparations, teriparatide, or denosumab.
The participant has been treated with any of the following drugs within 8 weeks prior to VISIT 2: oral contraceptive or sex hormone preparations (norethindrone, norethisterone, medroxyprogesterone, estrogen, or other progestins), and within 16 weeks prior to VISIT 2: gonadotropin-releasing hormone (GnRH) analogues, dienogest, danazol, or aromatase inhibitors (for 1- and 3-month sustained-release preparations, within 20 and 28 weeks prior to VISIT 2, respectively).
The participant has been treated with a bisphosphonate preparation within 24 weeks prior to VISIT 2.
The participant has a previous or current history of hypersensitivity or allergies to leuprorelin, synthetic GnRH, GnRH agonists or GnRH antagonists, or has a previous or current history of severe hypersensitivity or severe allergy to other drugs.
The participant has nondiagnosable abnormal genital bleeding.
Female participant who is pregnant, lactating, or intending to become pregnant or to donate ova prior to the signing of informed consent, during the study period, or within 1 month after the end of the study.
The participant has a previous or current history of osteoporosis, osteopenia, or other metabolic bone diseases.
The participant has clinically significant cardiovascular disease (eg, myocardial infarction or unstable angina pectoris within 24 weeks prior to VISIT 1) or uncontrollable hypertension (eg, resting systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg at Screening and Run-in).
The participant is inappropriate for participation in this study based on standard 12-lead electrocardiogram (ECG) findings, as determined by the investigator or subinvestigator.
The participant has active liver disease or jaundice, or with alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin (total bilirubin) > 1.5 times the upper limit of normal (ULN) in the clinical laboratory tests at VISITs 1 and 2.
The participant has previous or current history of diseases considered to be inappropriate for participation in this study, including severe hepatic impairment, jaundice, renal impairment, cardiovascular disease, endocrine system disease, metabolic disorder, pulmonary disease, gastrointestinal disease, neurological disease, urological disease, immune disease, or mental disorder (especially depression-like symptoms) or suicide attempt resulting from a mental disorder.
The participant has a previous or current history of drug abuse (defined as any illicit drug use) or alcohol abuse.
The participant is inappropriate for participation in this study for other reasons, as determined by the investigator or subinvestigator.

Name	Affiliation	Role
Medical Director	Takeda	Study Director

PubMed Identifier	Type	Citation	Retractions
30741797	Derived	Osuga Y, Enya K, Kudou K, Tanimoto M, Hoshiai H. Oral Gonadotropin-Releasing Hormone Antagonist Relugolix Compared With Leuprorelin Injections for Uterine Leiomyomas: A Randomized Controlled Trial. Obstet Gynecol. 2019 Mar;133(3):423-433. doi: 10.1097/AOG.0000000000003141.

ID	Title	Description
FG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 24, 2015	May 15, 2018

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00082.2(75.773 to 88.672) OG00183.1(76.935 to 89.263)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Farrington and Manning (FM)		0.0013		Difference in percentage	-0.9			2-Sided	95	-10.098	8.346			Relugolix 40 mg-Leuprorelin		Non-Inferiority	The point estimate and 2-sided 95% confidence interval of the difference in the percentage were calculated between Relugolix 40 mg group and leuprorelin group (Relugolix 40 mg group - leuprorelin group), using Farrington and Manning (FM) method. If the lower boundary of the 95% CI was greater or equal to the non-inferiority margin of -15%, then the non-inferiority of Relugolix 40 mg to leuprorelin was concluded.

Secondary

Percentage of Participants With Total PBAC Score of <10 From Week 2 to 6

FAS included all participants who were randomized and received at least 1 dose of the study drug for the treatment period. The number analyzed is the number of participants with data available for analysis at the given time-point.

Posted

Number

percentage of participants

Week 2 to 6

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Secondary

Percentage of Participants With Total PBAC Score of <10 From Week 18 to 24

Posted

Number

percentage of participants

Week 18 to 24

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Secondary

Percentage of Participants With Total PBAC Score of <10 for 6 Weeks Before the Final Dose of Study Drug

Posted

Number

percentage of participants

For 6 weeks before the final dose of study drug (up to Week 24)

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg

Secondary

Percent Change From Baseline in Myoma Volumes at Weeks 2, 4, 8, 12 and 24

A transvaginal ultrasound was performed to determine myoma volumes. Only the largest myoma among those measurable at visit 1 was measured throughout the study. On the assumption that the myoma was spheroids, the myoma volumes were calculated using 3 diameters (D1, D2, and D3). D1: the longest diameter of the myoma; D2: the longest diameter of the myoma which was perpendicular to D1; D3: the diameter of the myoma which crossed the intersection of D1 and D2 (intersection "Z") and was perpendicular to D1/D2 plane. The formula used for calculation is Myoma volume= D1*D2*D3*π/6.

Posted

Mean

Standard Deviation

cm^3

Baseline, Weeks 2, 4, 8, 12 and 24

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Secondary

Percent Change From Baseline in Uterine Volumes at Weeks 2, 4, 8, 12 and 24

A transvaginal ultrasound was performed for determination of uterine volumes. On the assumption that the uterus was spheroids, the uterine volumes were calculated using 3 diameters (D1, D2, and D3) measured as shown below: D1: the longest diameter of the uterus (unit of length: cm); D2: the longest diameter of the uterus which was perpendicular to D1 (unit of length: cm); D3: the diameter of the uterus which crossed the intersection of D1 and D2 (intersection "Z") and was perpendicular to D1/D2 plane (unit of length: cm). The formula used for calculation is Uterine volume=D1*D2*D3*π/6.

Posted

Mean

Standard Deviation

cm^3

Baseline, Weeks 2, 4, 8, 12 and 24

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Secondary

Change From Baseline in Hemoglobin at Weeks 4, 8, 12, 16, 20, 24 and Follow up

Anemia-related measurements consisted of hemoglobin, which were determined at the central laboratory.

Posted

Mean

Standard Deviation

g/dL

Baseline, Weeks 4, 8, 12, 16, 20, 24 and Follow up (up to Week 28)

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Secondary

Numerical Rating Scale (NRS) Score

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.

Posted

Mean

Standard Deviation

score on a scale

From Week 6 to 12, from Week 2 to 6, from Week 18 to 24, and for 6 weeks before the final dose (up to Week 24)

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Secondary

Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- Symptom Severity Score at Weeks 4, 8, 12, 16, 20, 24 and Follow-up

Posted

Mean

Standard Deviation

score on a scale

Baseline, Weeks 4, 8, 12, 16, 20, 24 and Follow-up (up to Week 28)

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Secondary

Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- HRQL Total Scores at Weeks 4, 8, 12, 16, 20, 24 and Follow-up

UFS-QOL was a 37-item self-reporting tool for evaluating QOL in participants with uterine fibroid. It includes eight symptom-related questions and 29 HRQL questions across six subscales (concern, activities, energy/mood, control, self-consciousness, sexual function). The total HRQL score is ranging from 0 to 100. The higher scores indicate better QOL.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Weeks 4, 8, 12, 16, 20, 24 and Follow-up (up to Week 28)

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Secondary

Number of Participants Who Had One or More Treatment Emergent Adverse Event (TEAE)

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.

Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.

Posted

Count of Participants

Participants

Up to Week 28

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Secondary

Number of Participants With Markedly Abnormal Values of Vital Signs

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]) is reported.

Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.

Posted

Count of Participants

Participants

Up to Week 28

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Secondary

Number of Participants With TEAE Related to Weight

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

Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.

Posted

Count of Participants

Participants

Up to Week 28

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Units	Counts

Secondary

Number of Participants With TEAE Related to Standard 12-Lead ECGs

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

Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.

Posted

Count of Participants

Participants

Up to Week 28

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Units	Counts

Secondary

Number of Participants With Markedly Abnormal Values of Laboratory Test

Number of participants with any markedly abnormal values in laboratory tests collected throughout study is reported. WBC = White blood cells, AST = Aspartate Aminotransferase, ALT = Alanine Aminotransferase, GGT = gamma-glutamyl transferase, ULN = upper limit of normal or upper reference limit.

Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.

Posted

Count of Participants

Participants

Up to Week 28

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Secondary

Number of Participants With TEAE (Bone Density Decreased) Related to Bone Mineral Density

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

Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.

Posted

Count of Participants

Participants

Up to Week 28

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Secondary

Number of Participants With TEAE Related to Biochemical Bone Metabolism Markers

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

Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.

Posted

Count of Participants

Participants

Up to Week 28

ID	Title	Description
OG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
OG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Malaise	General disorders	MedDRA version: 20.0	Systematic Assessment	EG0008 affected138 at risk EG0015 affected142 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA version: 20.0	Systematic Assessment	EG00039 affected138 at risk EG00146 affected142 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA version: 20.0	Systematic Assessment	EG0007 affected138 at risk EG0019 affected142 at risk
Bone density decreased	Investigations	MedDRA version: 20.0	Systematic Assessment	EG0006 affected138 at risk EG0018 affected142 at risk
Bone resorption test abnormal	Investigations	MedDRA version: 20.0	Systematic Assessment	EG0007 affected138 at risk EG0017 affected142 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version: 20.0	Systematic Assessment	EG0008 affected138 at risk EG0019 affected142 at risk
Resorption bone increased	Musculoskeletal and connective tissue disorders	MedDRA version: 20.0	Systematic Assessment	EG0007 affected138 at risk EG0018 affected142 at risk
Headache	Nervous system disorders	MedDRA version: 20.0	Systematic Assessment	EG00021 affected138 at risk EG00114 affected142 at risk
Dizziness	Nervous system disorders	MedDRA version: 20.0	Systematic Assessment	EG0009 affected138 at risk EG0017 affected142 at risk
Somnolence	Nervous system disorders	MedDRA version: 20.0	Systematic Assessment	EG0007 affected138 at risk EG0016 affected142 at risk
Metrorrhagia	Reproductive system and breast disorders	MedDRA version: 20.0	Systematic Assessment	EG00068 affected138 at risk EG00193 affected142 at risk
Menorrhagia	Reproductive system and breast disorders	MedDRA version: 20.0	Systematic Assessment	EG00034 affected138 at risk EG00122 affected142 at risk
Genital haemorrhage	Reproductive system and breast disorders	MedDRA version: 20.0	Systematic Assessment	EG0007 affected138 at risk EG0017 affected142 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA version: 20.0	Systematic Assessment	EG00013 affected138 at risk EG00115 affected142 at risk
Hot flush	Vascular disorders	MedDRA version: 20.0	Systematic Assessment	EG00059 affected138 at risk EG00175 affected142 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Nagoya	Aichi-ken		Japan

ID	Term
D009379	Neoplasms, Muscle Tissue
D018204	Neoplasms, Connective and Soft Tissue
D009370	Neoplasms by Histologic Type
D009369	Neoplasms

ID	Term
D007987	Gonadotropin-Releasing Hormone
D010906	Pituitary Hormone-Releasing Hormones
D007028	Hypothalamic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D009479	Neuropeptides
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D009842	Oligopeptides
D009419	Nerve Tissue Proteins
D011506	Proteins

ID	Title	Description
BG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
BG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Relugolix 40 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.	0	138	0	138	123	138
EG001	Leuprorelin 1.88 mg or 3.75 mg	Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.	0	142	2	142	134	142

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Large intestine polyp	Gastrointestinal disorders	MedDRA version: 20.0	Systematic Assessment		EG0000 affected138 at risk EG0011 affected142 at risk
Ulna fracture	Injury, poisoning and procedural complications	MedDRA version: 20.0	Systematic Assessment		EG0000 affected138 at risk EG0011 affected142 at risk