A Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer

Prostate Cancer Clinical Trial

— HERO  

Official title:

HERO: A Multinational Phase 3 Randomized, Open-label, Parallel Group Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03085095
• Other study ID #: MVT-601-3201
• Secondary ID: 2017-000160-15
• Status: Completed
• Phase: Phase 3
• Start date: April 18, 2017
• Est. completion date: November 26, 2021

Study information

• Verified date: January 2022
• Source: Myovant Sciences GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the efficacy and safety of relugolix 120 milligrams (mg) orally once daily for 48 weeks on maintaining serum testosterone suppression to castrate levels (< 50 nanograms/deciliter [ng/dL]) in participants with androgen-sensitive advanced prostate cancer.

Description:

This is a phase 3, multinational, randomized, open-label, parallel group study to evaluate the efficacy and safety of oral daily relugolix 120 mg in participants with androgen-sensitive advanced prostate cancer who require at least 1 year of continuous androgen-deprivation therapy. Relugolix 120 mg orally once daily or leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan based on local labels), every 3 months by subcutaneous injection will be administered to participants.

There are 2 analyses for this study, a primary analysis and a final analysis.

Primary Analysis:

The primary analysis of efficacy and safety has been completed (N=934). Participants were randomized 2:1 to receive relugolix or leuprolide for 48 weeks, followed by a 30-day safety follow-up visit or early termination 30-day safety follow-up.

Final Analysis:

The final analysis will occur after additional participants with metastatic disease (approximately 130) have been enrolled and randomized from any sites to the study, and have completed the 48-week treatment period. A cohort of participants enrolled in China and Taiwan will be analyzed separately once they have completed treatment to support registration in China.

Eligible participants were randomized 2:1 to relugolix or leuprolide arm and will attend visits monthly (every 4 weeks) where serum testosterone and prostate-specific antigen will be assessed. Safety will be assessed throughout the study by monitoring adverse events, vital signs, physical examinations, clinical laboratory tests, and 12-lead electrocardiograms.

Castration resistance-free survival will be assessed up to Week 49, Day 1 of the study and reported as part of the final analysis.

The study enrolled 1134 participants, including 139 participants with metastatic advanced prostate cancer to support the analysis of the secondary endpoint of castration resistance-free survival and 93 Chinese participants (enrolled in China and Taiwan) to support registration in China.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1134
• Est. completion date: November 26, 2021
• Est. primary completion date: October 25, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Has histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate.

2. Is a candidate for, in the opinion of the investigator, at least 1 year of continuous androgen deprivation therapy for the management of androgen-sensitive advanced prostate cancer with 1 of the following clinical disease state presentations:

1. Evidence of biochemical (PSA) or clinical relapse following local primary intervention with curative intent, such as surgery, radiation therapy, cryotherapy, or high-frequency ultrasound and not a candidate for salvage treatment by surgery; or

2. Newly diagnosed androgen-sensitive metastatic disease; or

3. Advanced localized disease unlikely to be cured by local primary intervention with either surgery or radiation with curative intent.

3. Has a serum testosterone at the Screening visit of = 150 ng/dL (5.2 nanomoles [nmol]/liter [L]).

4. Has a serum PSA concentration at the Screening visit of > 2.0 ng/milliliter (mL) (2.0 microgram [µg]/L), or, when applicable, post radical prostatectomy of > 0.2 ng/mL (0.2 µg/L) or post radiotherapy, cryotherapy, or high frequency ultrasound > 2.0 ng/mL (2.0 µg/L) above the post interventional nadir.

5. Has an Eastern Cooperative Oncology Group performance status of 0 or 1 at initial screening and at baseline.

Key Exclusion Criteria:

1. In the investigator's opinion, is likely to require chemotherapy or surgical therapy for symptomatic disease management within 2 months of initiating androgen deprivation therapy.

2. Previously received gonadotropin-releasing hormone analog or other form of androgen deprivation therapy (estrogen or antiandrogen) for > 18 months total duration. If androgen deprivation therapy was received for = 18 months total duration, then that therapy must have been completed at least 3 months prior to baseline. If the dosing interval of the depot is longer than 3 months, then the prior androgen deprivation therapy must have been completed at least as long as the dosing interval of the depot.

3. Previous systemic cytotoxic treatment for prostate cancer (for example, taxane-based regimen).

4. Metastases to brain per prior clinical evaluation.

5. Participants with myocardial infarction, unstable symptomatic ischemic heart disease, cerebrovascular events, or any significant cardiac condition within the prior 6 months.

6. Active conduction system abnormalities.

7. Uncontrolled hypertension.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Relugolix
Relugolix 120-mg tablet administered orally once daily following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1
• Leuprolide Acetate
Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan, Taiwan, and China), every 3 months by subcutaneous injection

Locations

Country	Name	City	State
Australia	Camperdown	Camperdown	New South Wales
Australia	Redcliffe	Redcliffe	Queensland
Australia	Southport	Southport	Queensland
Australia	Tweed Heads	Tweed Heads	New South Wales
Australia	Wahroonga	Wahroonga	New South Wales
Austria	Linz	Linz
Belgium	Brussels	Brussels
Belgium	Gent	Gent	Oost-Vlaanderen
Belgium	Kortrijk	Kortrijk
Brazil	Curitiba	Curitiba
Brazil	Ijuí	Ijuí	Rio Grande Do Sul
Brazil	Itabuna	Itabuna	Bahia
Brazil	Joinville	Joinville	Santa Catarina
Brazil	Natal	Natal	Rio Grande Do Norte
Brazil	Passo Fundo	Passo Fundo	Rio Grande Do Sul
Brazil	Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Salvador	Salvador	Bahia
Brazil	Salvador	Salvador	Bahia
Brazil	São José Do Rio Preto	São José Do Rio Preto	Sao Paulo
Brazil	Teresina	Teresina	Piauí
Canada	Calgary	Calgary	Alberta
Canada	Halifax	Halifax	Nova Scotia
Canada	Hamilton	Hamilton	Ontario
Canada	London	London	Ontario
Canada	Montreal	Montréal	Quebec
Canada	Quebec	Quebec
Canada	Sherbrooke	Sherbrooke	Quebec
Canada	Vancouver	Vancouver	British Columbia
China	Beijing	Beijing
China	Beijing	Beijing
China	Beijing Shi	Beijing
China	Changchun	Chang chun	Jilin
China	Chongqing	Chongqing
China	Hangzhou	Hangzhou
China	Lanzhou	Lanzhou
China	Nanchang	Nanchang
China	Nanjing	Nanjing	Jiangsu
China	Shanghai	Shanghai	Shanghai
China	Shanghai	Shanghai
China	Suzhou	Suzhou
China	Taiyuan	Taiyuan	Shanxi
Denmark	Alborg	Aalborg
Denmark	Aarhus	Aarhus
Denmark	Herlev	Herlev
Denmark	Vejle	Vejle
Finland	Helsinki	Helsinki
Finland	Seinajoki	Seinäjoki
Finland	Tampere	Tampere
Finland	Turku	Turku
France	Creteil	Créteil	Val-de-Marne
France	Lyon	Lyon
France	Pierre Benite	Pierre-Bénite	Rhone
France	Strasbourg	Strasbourg	Bas-Rhin
Germany	Braunschweig	Braunschweig	Niedersachsen
Germany	Dresden	Dresden
Germany	Emmendingen	Emmendingen	Baden-Wurttemberg
Germany	Lubeck	Lübeck
Germany	Munster	Münster
Germany	Planegg	Planegg	Bayern
Italy	Arezzo	Arezzo	Toscana
Italy	Candiolo	Candiolo	Piemonte
Italy	Cremona	Cremona	Lombardia
Italy	Meldola	Meldola	Emilia-Romagna
Italy	Milano	Milano
Italy	Orbassano	Orbassano	Piemonte
Italy	Rome	Rome	Lazio
Japan	Bunkyo-Ku	Bunkyo-Ku	Tokyo
Japan	Chiba	Chiba
Japan	Fukuoka	Fukuoka
Japan	Hiroshima	Hiroshima
Japan	Kanazawa-shi	Kanazawa-shi	Isikawa
Japan	Kita-gun	Kita
Japan	Kyoto	Kyoto
Japan	Maebashi	Maebashi
Japan	Nagasaki	Nagasaki
Japan	Nakano-ku	Nakano-ku	Tokyo
Japan	Osaka	Osaka
Japan	Osaka-sayama	Osaka-sayama	Osaka
Japan	Sapporo	Sapporo
Japan	Sendai	Sendai	Miyagi
Japan	Sendai	Sendai	Miyagi
Japan	Suita	Suita	Osaka
Japan	Sumida-ku	Sumida-ku	Tokyo
Japan	Tokyo	Tokyo
Japan	Ube	Ube
Japan	Yokohama	Yokohama	Kanagawa
Korea, Republic of	Busan	Busan
Korea, Republic of	Daegu	Daegu
Korea, Republic of	Goyang-Si	Goyang-si	Gyeonggido
Korea, Republic of	Hwasun	Hwasun
Korea, Republic of	Seoul	Seoul
Korea, Republic of	Seoul	Seoul
Korea, Republic of	Seoul	Seoul
Korea, Republic of	Seoul	Seoul
Netherlands	Amsterdam	Amsterdam	Noord Holland
Netherlands	Eindhoven	Eindhoven	Noord Brabant
Netherlands	Sneek	Sneek
New Zealand	Christchurch	Christchurch
New Zealand	Dunedin	Dunedin
New Zealand	Hamilton	Hamilton
New Zealand	Tauranga	Tauranga
Poland	Gdynia	Gdynia	Pomorskie
Poland	Katowice	Katowice
Poland	Lublin	Lublin	Lubelskie
Poland	Siedlce	Siedlce	Mazowieckie
Poland	Warszawa	Warszawa	Mazowieckie
Slovakia	Sala	Šala
Slovakia	Bratislava	Bratislava
Slovakia	Kosice	Košice
Slovakia	Kosice	Košice
Slovakia	Martin	Martin
Slovakia	Nitra	Nitra
Slovakia	Poprad	Poprad
Slovakia	Presov	Prešov
Slovakia	Trencin	Trencín
Spain	A Coruna	A Coruña	A Coruna
Spain	Barcelona	Barcelona
Spain	Madrid	Madrid
Spain	Madrid	Madrid
Spain	Oviedo	Oviedo	Asturias
Spain	Salamanca	Salamanca
Spain	Valencia	Valencia
Sweden	Malmo	Malmö
Sweden	Orebro	Örebro	Orebro Ian
Sweden	Stockholm	Stockholm	Sodermandlands Ian
Sweden	Uppsala	Uppsala	Uppsala Lan
Taiwan	Kaohsiung City	Kaohsiung City
Taiwan	Taipei	Taipei
Taiwan	Taipei	Taipei
Taiwan	Taipei	Taipei
United Kingdom	Exeter	Exeter	Devon
United Kingdom	Nottingham	Nottingham
United Kingdom	Rhyl	Rhyl
United Kingdom	Scunthorpe	Scunthorpe	North Lincolnshire
United States	Albany	Albany	New York
United States	Albuquerque	Albuquerque	New Mexico
United States	Baltimore	Baltimore	Maryland
United States	Brick	Brick	New Jersey
United States	Cincinnati	Cincinnati	Ohio
United States	Denver	Denver	Colorado
United States	Des Moines	Des Moines	Iowa
United States	Durham	Durham	North Carolina
United States	Garden City	Garden City	New York
United States	Greensboro	Greensboro	North Carolina
United States	Jeffersonville	Jeffersonville	Indiana
United States	Lancaster	Lancaster	Pennsylvania
United States	Las Vegas	Las Vegas	Nevada
United States	Middleburg Heights	Middleburg Heights	Ohio
United States	Myrtle Beach	Myrtle Beach	South Carolina
United States	Nashville	Nashville	Tennessee
United States	Oklahoma City	Oklahoma City	Oklahoma
United States	Omaha	Omaha	Nebraska
United States	Orange	Orange	California
United States	Plainview	Plainview	New York
United States	Pompano Beach	Pompano Beach	Florida
United States	Poughkeepsie	Poughkeepsie	New York
United States	San Antonio	San Antonio	Texas
United States	Syracuse	Syracuse	New York
United States	Troy	Troy	Michigan
United States	Tucson	Tucson	Arizona
United States	Wichita	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Myovant Sciences GmbH

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Denmark,  Finland,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Slovakia,  Spain,  Sweden,  Taiwan,  United Kingdom, 

References & Publications (1)

Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, Akaza H, Bossi A, van Veenhuyzen DF, Selby B, Fan X, Kang V, Walling J, Tombal B; HERO Study Investigators. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187-2196. doi: 10.1056/NEJMoa2004325. Epub 2020 May 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants Who Experienced Major Adverse Cardiovascular Events (MACE)	MACE were defined as nonfatal myocardial infarction, nonfatal stroke, and death from any cause.	From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)
Primary	Sustained Castration Rate	Sustained castration rate defined as the cumulative probability of testosterone suppression to < 50 nanogram (ng)/deciliter (dL). The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.; The lower bound of the 95% confidence interval (CI) for the cumulative probability of sustained testosterone suppression in the relugolix treatment group must have been = 90% to meet evaluation criteria for efficacy.	From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)
Secondary	Castration Rate At Week 1 Day 4	Castration rate was defined as the cumulative probability of testosterone suppression to < 50 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.	Week 1 Day 4 (Day 4)
Secondary	Castration Rate At Week 3 Day 1	Castration rate was defined as the cumulative probability of testosterone suppression to < 50 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.	Week 3 Day 1 (Day 15)
Secondary	Confirmed Prostate-specific Antigen (PSA) Response Rate	Confirmed PSA response defined as > 50% reduction in PSA from baseline at Week 3 Day 1 followed with confirmation at Week 5 Day 1.	Week 3 Day 1 (Day 15) and Week 5 Day 1 (Day 29)
Secondary	Profound Castration Rate At Week 3 Day 1 (Day 15)	Castration rate defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.	Week 3 Day 1 (Day 15)
Secondary	Follicle-stimulating Hormone (FSH) Level	To evaluate the effect of relugolix and leuprolide acetate on FSH suppression.	Week 25 Day 1 (Day 169)
Secondary	PSA Response Rate At Week 3 Day 1	PSA response defined as > 50% reduction in PSA from baseline. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.	Week 3 Day 1 (Day 15)
Secondary	PSA Response Rate At Week 5 Day 1	PSA response defined as > 50% reduction in PSA from baseline. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.	Week 5 Day 1 (Day 29)
Secondary	Testosterone Recovery Rate	The cumulative probability of testosterone recovery back to > 280 ng/dL (lower limit of the normal range), back to = 50 ng/dL (definition of castration), and back to > 280 ng/dL or baseline at 90 days after drug discontinuation was assessed. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.	Day 90 follow-up
Secondary	Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1	Sustained profound castration rate was defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.	Week 5 Day 1 (Day 29) through Week 49 Day 1 (Day 337)
Secondary	Profound Castration Rate At Week 1 Day 4 (Day 4)	Castration rate defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.	At Week 1 Day 4 (Day 4)
Secondary	Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1	Sustained profound castration rate was defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.	Week 25 Day 1 (Day 169) through Week 49 Day 1 (Day 337)
Secondary	Undetectable PSA Rate	Defined as the proportion of participants with PSA concentration < 0.02 ng/milliliter (mL).The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.	Week 25 Day 1 (Day 169)
Secondary	Rate Of PSA Progression-free Survival	PSA progression was defined as the first increase in PSA of 25% or greater and 2 ng/mL or greater above the nadir with confirmation by a second consecutive PSA measurement at least 3 weeks later. For participants without declining PSA from baseline, a PSA increase of = 25% and = 2 ng/mL from baseline beyond 12 weeks was considered PSA progression. The rate of progression-free survival was estimated using the Kaplan-Meier method and reported as percentage of participants.	Week 49 Day 1 (Day 337)
Secondary	Change From Baseline In Quality Of Life (QoL) Total Score As Assessed By The Global Health Domain Of The European Organisation Of Research And Treatment Of Cancer (EORTC)-Quality Of Life Questionnaire (QLQ)-C30	The EORTC QLQ-C30 core measurement was used to capture distal outcomes, including physical, social functioning, and overall health-related quality of life. The questionnaire incorporates 30 questions comprising nine multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 3 symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality of life scale. All raw domain scores are linearly transformed to a 0-100 scale. The global health and quality of life domain is presented. An increase in activity or functioning scores indicates improvement (higher/healthier level of functioning) and a decrease in symptom scores indicates improvement (lower level of symptoms/problems).	Baseline, Week 49 Day 1 (Day 337)
Secondary	Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30	The EORTC QLQ-C30 core measurement was used to capture distal outcomes, including physical, social functioning, and overall health-related quality of life. The questionnaire incorporates 30 questions comprising nine multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 3 symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality of life scale. All raw domain scores are linearly transformed to a 0-100 scale. All domains except for the global health and quality are presented. An increase in activity or functioning scores indicates improvement (higher/healthier level of functioning) and a decrease in symptom scores indicates improvement (lower level of symptoms/problems).	Baseline, Week 49 Day 1 (Day 337)
Secondary	Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains	Subscales for assessment of hormonal treatment-related symptoms (6 items) and sexual activity and function (6 items) from the EORTC-QLQ-PR25 25-item prostate cancer module of the EORTC are presented. Questions used 4 point scale (1 'Not at all' to 4 'Very much'). All raw domain scores are linearly transformed to a 0-100 scale. An increase in activity or functioning scores indicates improvement (higher/healthier level of functioning) and a decrease in symptom scores indicates improvement (lower level of symptoms/problems).	Baseline, Week 49 Day 1 (Day 337)
Secondary	Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25	Subscale assessments of urinary symptoms (9 items) and bowel symptoms (4 items) from the EORTC-QLQ-PR25 25-item prostate cancer module of the EORTC are presented. Questions used 4 point scale (1 'Not at all' to 4 'Very much'). All raw domain scores are linearly transformed to a 0-100 scale. A decrease in symptom scores indicates improvement (lower level of symptoms/problems).	Baseline, Week 49 Day 1 (Day 337)
Secondary	Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire (EuroQoL EQ-5D-5L)	The EuroQoL EQ-5D-5L comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 levels: no problems (1 as numerical score), slight problems (2 as numerical score), moderate problems (3 as numerical score), severe problems (4 as numerical score), and extreme problems (5 as numerical score). The total score ranges from 0 to 100. A decrease in score indicates improvement.	Baseline, Week 49 Day 1 (Day 337)
Secondary	Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone	Blood samples were collected from participants for hormonal measurements.	Week 1 Day 4 (Day 4), Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
Secondary	Percent Change From Baseline In Serum Concentrations Of FSH	Blood samples were collected from participants for hormonal measurements.	Week 1 Day 4 (Day 4), Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
Secondary	Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone	Blood samples were collected from participants for hormonal measurements.	Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
Secondary	Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin	Blood samples were collected from participants for hormonal measurements.	Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
Secondary	Maximum Observed Plasma Concentration (Cmax) Of Relugolix	The Cmax of relugolix was determined for single and repeat doses in subsets of participants from Japan. Single dose pharmacokinetics (PK) was assessed on Day 1 following an initial 360 mg dose of relugolix. Repeat dose PK was assessed following repeat dosing of relugolix 120 mg once daily for 2 weeks.	Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2
Secondary	Area Under The Concentration-Time Curve (AUC0-t) Of Relugolix	The AUC0-t of relugolix was determined for single and repeat doses in subsets of participants from Japan. Single dose PK was assessed on Day 1 following an initial 360 mg dose of relugolix. Repeat dose PK was assessed following repeat dosing of relugolix 120 mg once daily for 2 weeks.	Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2
Secondary	Time To Maximum Observed Plasma Concentration (Tmax) Of Relugolix	The Tmax of relugolix was determined for single and repeat doses in subsets of participants from Japan. Single dose PK was assessed on Day 1 following an initial 360 mg dose of relugolix. Repeat dose PK was assessed following repeat dosing of relugolix 120 mg once daily for 2 weeks.	Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2