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

• Sponsor: Myovant Sciences GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03085095
• Collaborator: (none)
• Enrollment: 1,134
• Locations: 162
• Arms: 2
• Actual Duration (Months): 55.3
• Patients Per Site: 7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Relugolix; Drug: Leuprolide Acetate	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1134 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Apr 18, 2017
• Actual Primary Completion Date: Oct 25, 2019
• Actual Study Completion Date: Nov 26, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Relugolix Relugolix for 48 weeks	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; Other Names: TAK-385 MVT-601 RVT-601 T-1331285
Active Comparator: Leuprolide Acetate Leuprolide acetate for 48 weeks	Drug: Leuprolide Acetate; Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan, Taiwan, and China), every 3 months by subcutaneous injection; Other Names: Leuprolide

Outcome Measures

Primary Outcome Measures

1. Sustained Castration Rate [From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)]

   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.

Secondary Outcome Measures

1. Castration Rate At Week 1 Day 4 [Week 1 Day 4 (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.

2. Castration Rate At Week 3 Day 1 [Week 3 Day 1 (Day 15)]

   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.

3. Confirmed Prostate-specific Antigen (PSA) Response Rate [Week 3 Day 1 (Day 15) and Week 5 Day 1 (Day 29)]

   Confirmed PSA response defined as > 50% reduction in PSA from baseline at Week 3 Day 1 followed with confirmation at Week 5 Day 1.

4. Profound Castration Rate At Week 3 Day 1 (Day 15) [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.

5. Follicle-stimulating Hormone (FSH) Level [Week 25 Day 1 (Day 169)]

   To evaluate the effect of relugolix and leuprolide acetate on FSH suppression.

6. PSA Response Rate At Week 3 Day 1 [Week 3 Day 1 (Day 15)]

   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.

7. PSA Response Rate At Week 5 Day 1 [Week 5 Day 1 (Day 29)]

   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.

8. Testosterone Recovery Rate [Day 90 follow-up]

   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.

9. Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1 [Week 5 Day 1 (Day 29) through Week 49 Day 1 (Day 337)]

   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.

10. Profound Castration Rate At Week 1 Day 4 (Day 4) [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.

11. Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1 [Week 25 Day 1 (Day 169) through Week 49 Day 1 (Day 337)]

    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.

12. Undetectable PSA Rate [Week 25 Day 1 (Day 169)]

    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.

13. Rate Of PSA Progression-free Survival [Week 49 Day 1 (Day 337)]

    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.

14. 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 [Baseline, Week 49 Day 1 (Day 337)]

    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).

15. Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 [Baseline, Week 49 Day 1 (Day 337)]

    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).

16. Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains [Baseline, Week 49 Day 1 (Day 337)]

    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).

17. Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25 [Baseline, Week 49 Day 1 (Day 337)]

    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).

18. Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire (EuroQoL EQ-5D-5L) [Baseline, Week 49 Day 1 (Day 337)]

    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.

19. Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone [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)]

    Blood samples were collected from participants for hormonal measurements.

20. Percent Change From Baseline In Serum Concentrations Of FSH [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)]

    Blood samples were collected from participants for hormonal measurements.

21. Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone [Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)]

    Blood samples were collected from participants for hormonal measurements.

22. Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin [Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)]

    Blood samples were collected from participants for hormonal measurements.

23. Maximum Observed Plasma Concentration (Cmax) Of Relugolix [Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2]

    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.

24. Area Under The Concentration-Time Curve (AUC0-τ) Of Relugolix [Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2]

    The AUC0-τ 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.

25. Time To Maximum Observed Plasma Concentration (Tmax) Of Relugolix [Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2]

    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.

Other Outcome Measures

1. Percentage of Participants Who Experienced Major Adverse Cardiovascular Events (MACE) [From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)]

   MACE were defined as nonfatal myocardial infarction, nonfatal stroke, and death from any cause.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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:

3. 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

4. Newly diagnosed androgen-sensitive metastatic disease; or

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

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

7. 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.

8. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tucson	Tucson	Arizona	United States	85741
2	Orange	Orange	California	United States	92868
3	Denver	Denver	Colorado	United States	80211
4	Pompano Beach	Pompano Beach	Florida	United States	33060
5	Jeffersonville	Jeffersonville	Indiana	United States	47130
6	Des Moines	Des Moines	Iowa	United States	50266
7	Wichita	Wichita	Kansas	United States	67226
8	Baltimore	Baltimore	Maryland	United States	21204
9	Troy	Troy	Michigan	United States	48084
10	Omaha	Omaha	Nebraska	United States	68130
11	Las Vegas	Las Vegas	Nevada	United States	89135
12	Brick	Brick	New Jersey	United States	08724
13	Albuquerque	Albuquerque	New Mexico	United States	87109
14	Albany	Albany	New York	United States	12208
15	Garden City	Garden City	New York	United States	11530
16	Plainview	Plainview	New York	United States	11803
17	Poughkeepsie	Poughkeepsie	New York	United States	12601
18	Syracuse	Syracuse	New York	United States	13210
19	Durham	Durham	North Carolina	United States	27710
20	Greensboro	Greensboro	North Carolina	United States	27403
21	Cincinnati	Cincinnati	Ohio	United States	45212
22	Middleburg Heights	Middleburg Heights	Ohio	United States	44130
23	Oklahoma City	Oklahoma City	Oklahoma	United States	73104
24	Lancaster	Lancaster	Pennsylvania	United States	17604
25	Myrtle Beach	Myrtle Beach	South Carolina	United States	29572
26	Nashville	Nashville	Tennessee	United States	37209
27	San Antonio	San Antonio	Texas	United States	78258
28	Camperdown	Camperdown	New South Wales	Australia	2050
29	Tweed Heads	Tweed Heads	New South Wales	Australia	2485
30	Wahroonga	Wahroonga	New South Wales	Australia	2076
31	Redcliffe	Redcliffe	Queensland	Australia	4020
32	Southport	Southport	Queensland	Australia	4215
33	Linz	Linz		Austria	402
34	Gent	Gent	Oost-Vlaanderen	Belgium	9000
35	Brussels	Brussels		Belgium	1200
36	Kortrijk	Kortrijk		Belgium	8500
37	Itabuna	Itabuna	Bahia	Brazil	45602-650
38	Salvador	Salvador	Bahia	Brazil	41253-190
39	Salvador	Salvador	Bahia	Brazil	41820-021
40	Teresina	Teresina	Piauí	Brazil	64001-280
41	Natal	Natal	Rio Grande Do Norte	Brazil	59062-000
42	Ijuí	Ijuí	Rio Grande Do Sul	Brazil	98700
43	Passo Fundo	Passo Fundo	Rio Grande Do Sul	Brazil	99010-080
44	Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90110-270
45	Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90430-090
46	Joinville	Joinville	Santa Catarina	Brazil	89201-260
47	São José Do Rio Preto	São José Do Rio Preto	Sao Paulo	Brazil	15090-000
48	Curitiba	Curitiba		Brazil	81520-060
49	Calgary	Calgary	Alberta	Canada	T2V4R6
50	Vancouver	Vancouver	British Columbia	Canada	V5Z1M9
51	Halifax	Halifax	Nova Scotia	Canada	B3H2Y9
52	Hamilton	Hamilton	Ontario	Canada	L8N4A6
53	London	London	Ontario	Canada	N6A4G5
54	Montreal	Montréal	Quebec	Canada	H2X0A9
55	Sherbrooke	Sherbrooke	Quebec	Canada	J1H5N4
56	Quebec	Quebec		Canada	G1R 3S3
57	Nanjing	Nanjing	Jiangsu	China	210008
58	Changchun	Chang chun	Jilin	China	130021
59	Shanghai	Shanghai	Shanghai	China	020043
60	Taiyuan	Taiyuan	Shanxi	China	030001
61	Beijing	Beijing		China	100041
62	Beijing	Beijing		China	100050
63	Beijing Shi	Beijing		China	100730
64	Chongqing	Chongqing		China	400030
65	Hangzhou	Hangzhou		China	310003
66	Lanzhou	Lanzhou		China	730030
67	Nanchang	Nanchang		China	330006
68	Shanghai	Shanghai		China	200040
69	Suzhou	Suzhou		China	215004
70	Alborg	Aalborg		Denmark	DK-9000
71	Aarhus	Aarhus		Denmark	8200
72	Herlev	Herlev		Denmark	2730
73	Vejle	Vejle		Denmark	DK-7100
74	Helsinki	Helsinki		Finland	FI-00029
75	Seinajoki	Seinäjoki		Finland	FI-60220
76	Tampere	Tampere		Finland	FI-33520
77	Turku	Turku		Finland	FI-20520
78	Strasbourg	Strasbourg	Bas-Rhin	France	67091
79	Pierre Benite	Pierre-Bénite	Rhone	France	69495
80	Creteil	Créteil	Val-de-Marne	France	94010
81	Lyon	Lyon		France	69437
82	Emmendingen	Emmendingen	Baden-Wurttemberg	Germany	79312
83	Planegg	Planegg	Bayern	Germany	82152
84	Braunschweig	Braunschweig	Niedersachsen	Germany	38100
85	Dresden	Dresden		Germany	01307
86	Lubeck	Lübeck		Germany	23538
87	Munster	Münster		Germany	48149
88	Meldola	Meldola	Emilia-Romagna	Italy	47014
89	Rome	Rome	Lazio	Italy	00152
90	Cremona	Cremona	Lombardia	Italy	26100
91	Candiolo	Candiolo	Piemonte	Italy	10060
92	Orbassano	Orbassano	Piemonte	Italy	10043
93	Arezzo	Arezzo	Toscana	Italy	52100
94	Milano	Milano		Italy	20162
95	Kanazawa-shi	Kanazawa-shi	Isikawa	Japan	920-8641
96	Yokohama	Yokohama	Kanagawa	Japan	232-0024
97	Sendai	Sendai	Miyagi	Japan	9808574
98	Sendai	Sendai	Miyagi	Japan	9818563
99	Suita	Suita	Osaka	Japan	565-0871
100	Osaka-sayama	Ōsaka-sayama	Osaka	Japan	589-8511
101	Bunkyō-Ku	Bunkyō-Ku	Tokyo	Japan	113-8655
102	Nakano-ku	Nakano-ku	Tokyo	Japan	164-8541
103	Sumida-ku	Sumida-ku	Tokyo	Japan	130-8587
104	Chiba	Chiba		Japan	260-0801
105	Fukuoka	Fukuoka		Japan	812-0033
106	Hiroshima	Hiroshima		Japan	730-8518
107	Kita-gun	Kita		Japan	761-0793
108	Kyoto	Kyoto		Japan	606-8507
109	Maebashi	Maebashi		Japan	371-8511
110	Nagasaki	Nagasaki		Japan	852-8501
111	Osaka	Osaka		Japan	541-8567
112	Sapporo	Sapporo		Japan	003-0804
113	Tokyo	Tokyo		Japan	285-8741
114	Ube	Ube		Japan	7558505
115	Goyang-Si	Goyang-si	Gyeonggido	Korea, Republic of	10408
116	Busan	Busan		Korea, Republic of	49241
117	Daegu	Daegu		Korea, Republic of	41404
118	Hwasun	Hwasun		Korea, Republic of	58128
119	Seoul	Seoul		Korea, Republic of	03080
120	Seoul	Seoul		Korea, Republic of	05505
121	Seoul	Seoul		Korea, Republic of	06273
122	Seoul	Seoul		Korea, Republic of	06351
123	Eindhoven	Eindhoven	Noord Brabant	Netherlands	5623EJ
124	Amsterdam	Amsterdam	Noord Holland	Netherlands	1105AZ
125	Sneek	Sneek		Netherlands	8601 ZK
126	Christchurch	Christchurch		New Zealand	8013
127	Dunedin	Dunedin		New Zealand	9016
128	Hamilton	Hamilton		New Zealand	3204
129	Tauranga	Tauranga		New Zealand	3112
130	Lublin	Lublin	Lubelskie	Poland	20-582
131	Siedlce	Siedlce	Mazowieckie	Poland	08-110
132	Warszawa	Warszawa	Mazowieckie	Poland	02-797
133	Gdynia	Gdynia	Pomorskie	Poland	81-519
134	Katowice	Katowice		Poland	40611
135	Bratislava	Bratislava		Slovakia	851 05
136	Kosice	Košice		Slovakia	040 01
137	Kosice	Košice		Slovakia	041 91
138	Martin	Martin		Slovakia	036 59
139	Nitra	Nitra		Slovakia	949 01
140	Poprad	Poprad		Slovakia	058 45
141	Presov	Prešov		Slovakia	080 01
142	Trencin	Trenčín		Slovakia	911 01
143	Sala	Šaľa		Slovakia	927 01
144	A Coruna	A Coruña	A Coruna	Spain	15706
145	Oviedo	Oviedo	Asturias	Spain	33011
146	Barcelona	Barcelona		Spain	08036
147	Madrid	Madrid		Spain	28007
148	Madrid	Madrid		Spain	28041
149	Salamanca	Salamanca		Spain	37007
150	Valencia	Valencia		Spain	46009
151	Orebro	Örebro	Orebro Ian	Sweden	SE-70185
152	Stockholm	Stockholm	Sodermandlands Ian	Sweden	SE-17176
153	Uppsala	Uppsala	Uppsala Lan	Sweden	SE-751-85
154	Malmo	Malmö		Sweden	SE-20502
155	Kaohsiung City	Kaohsiung City		Taiwan	807
156	Taipei	Taipei		Taiwan	100
157	Taipei	Taipei		Taiwan	111
158	Taipei	Taipei		Taiwan	11490
159	Exeter	Exeter	Devon	United Kingdom	EX2 5DW
160	Scunthorpe	Scunthorpe	North Lincolnshire	United Kingdom	DN157BH
161	Nottingham	Nottingham		United Kingdom	NG5 1PB
162	Rhyl	Rhyl		United Kingdom	LL18 5UJ

Sponsors and Collaborators

• Myovant Sciences GmbH

Investigators

• Study Director: Myovant Medical Monitor, Myovant Sciences

Study Documents (Full-Text)

• Study Protocol - Oct 23, 2018
• Statistical Analysis Plan - Nov 7, 2019

More Information

Publications

• 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.

• Responsible Party: Myovant Sciences GmbH
• ClinicalTrials.gov Identifier: NCT03085095
• Other Study ID Numbers: MVT-601-3201; 2017-000160-15
• First Posted: Mar 21, 2017
• Last Update Posted: Jan 18, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Prostatic Neoplasms; Leuprolide; Relugolix

Study Results

Participant Flow

Recruitment Details	To support registration in China, the study continued to enroll additional nonmetastatic or metastatic participants from China after the final analysis to reach the target enrollment of approximately 90 participants.
Pre-assignment Detail	The primary analysis of efficacy and safety included 934 participants. The primary analysis excluded additional participants with metastatic disease and a cohort of participants enrolled in China and Taiwan who will be included in the final analysis of the study (N=200).

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-milligram (mg) tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Period Title: Overall Study
STARTED	624	310
Received at Least 1 Dose of Study Drug	622	308
COMPLETED	563	276
NOT COMPLETED	61	34

Baseline Characteristics

Arm/Group Title	Relugolix	Leuprolide Acetate	Total
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.	Total of all reporting groups
Overall Participants	622	308	930
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.2 (7.75)	71.0 (8.03)	71.1 (7.84)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	622 100%	308 100%	930 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	52 8.4%	31 10.1%	83 8.9%
Not Hispanic or Latino	558 89.7%	269 87.3%	827 88.9%
Unknown or Not Reported	12 1.9%	8 2.6%	20 2.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	127 20.4%	71 23.1%	198 21.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	30 4.8%	16 5.2%	46 4.9%
White	434 69.8%	202 65.6%	636 68.4%
More than one race	11 1.8%	4 1.3%	15 1.6%
Unknown or Not Reported	20 3.2%	15 4.9%	35 3.8%

Outcome Measures

1. Primary Outcome

Title	Sustained Castration Rate
Description	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.
Time Frame	From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Number (95% Confidence Interval) [percentage of participants]	96.7 15.5%	88.8 28.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Relugolix, Leuprolide Acetate
	Comments	Following statistical analysis of the lower bound of the 95% CI ≥ 90% for the relugolix group, secondary statistical analysis of non-inferiority was conducted.
	Type of Statistical Test	Non-Inferiority
	Comments	The lower bound of the 95% CI for the difference in the cumulative probability of sustained profound castration rate between the 2 treatment groups was calculated with a noninferiority margin of -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	7.9
	Confidence Interval	(2-Sided) 95%; 4.1 to 11.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference= Relugolix - Leuprolide acetate

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Relugolix, Leuprolide Acetate
	Comments	Following statistical analysis of the lower bound of the 95% CI ≥ 90% for the relugolix group, secondary statistical analysis of superiority was conducted.
	Type of Statistical Test	Superiority
	Comments	If non-inferiority was demonstrated, superiority could be claimed if the lower bound of the 95% CI for the difference in the cumulative probability of sustained profound castration rate between the 2 treatment groups also excluded 0%. The p value was calculated post hoc.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-test, 2 sided
	Comments	Two-sided type I error of 0.05.

2. Secondary Outcome

Title	Castration Rate At Week 1 Day 4
Description	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.
Time Frame	Week 1 Day 4 (Day 4)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Number (95% Confidence Interval) [percentage of participants]	56.04 9%	0.00 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Relugolix, Leuprolide Acetate
	Comments	Alpha-protected statistical analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Statistically significance was met if p-value < 0.05.
	Method	t-test, 2 sided
	Comments	Two-sided type I error rate of 0.05.

3. Secondary Outcome

Title	Castration Rate At Week 3 Day 1
Description	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.
Time Frame	Week 3 Day 1 (Day 15)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Number (95% Confidence Interval) [percentage of participants]	98.71 15.9%	12.05 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Relugolix, Leuprolide Acetate
	Comments	Alpha-protected statistical analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Statistically significance was met if p-value < 0.05.
	Method	t-test, 2 sided
	Comments	Two-sided type I error rate of 0.05.

4. Secondary Outcome

Title	Confirmed Prostate-specific Antigen (PSA) Response Rate
Description	Confirmed PSA response defined as > 50% reduction in PSA from baseline at Week 3 Day 1 followed with confirmation at Week 5 Day 1.
Time Frame	Week 3 Day 1 (Day 15) and Week 5 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Number (95% Confidence Interval) [percentage of participants]	79.4 12.8%	19.8 6.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Relugolix, Leuprolide Acetate
	Comments	Alpha-protected statistical analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Statistically significance was met if p-value < 0.05.
	Method	Cochran-Mantel-Haenszel
	Comments

5. Secondary Outcome

Title	Profound Castration Rate At Week 3 Day 1 (Day 15)
Description	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.
Time Frame	Week 3 Day 1 (Day 15)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Number (95% Confidence Interval) [percentage of participants]	78.38 12.6%	0.98 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Relugolix, Leuprolide Acetate
	Comments	Alpha-protected statistical analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Statistically significance was met if p-value < 0.05.
	Method	t-test, 2 sided
	Comments	Two-sided type I error rate of 0.05.
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	77.41
	Confidence Interval	(2-Sided) 95%; 73.98 to 80.83
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference= Relugolix - Leuprolide acetate

6. Secondary Outcome

Title	Follicle-stimulating Hormone (FSH) Level
Description	To evaluate the effect of relugolix and leuprolide acetate on FSH suppression.
Time Frame	Week 25 Day 1 (Day 169)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Mean (Standard Deviation) [IU/L]	1.72 (1.376)	5.95 (3.071)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Relugolix, Leuprolide Acetate
	Comments	Alpha-protected statistical analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Statistically significance was met if p-value < 0.05.
	Method	t-test, 2 sided
	Comments	Two-sided type I error rate of 0.05.

7. Secondary Outcome

Title	PSA Response Rate At Week 3 Day 1
Description	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.
Time Frame	Week 3 Day 1 (Day 15)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Number (95% Confidence Interval) [percentage of participants]	80.1 12.9%	20.1 6.5%

8. Secondary Outcome

Title	PSA Response Rate At Week 5 Day 1
Description	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.
Time Frame	Week 5 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Number (95% Confidence Interval) [percentage of participants]	94.5 15.2%	79.2 25.7%

9. Secondary Outcome

Title	Testosterone Recovery Rate
Description	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.
Time Frame	Day 90 follow-up

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and were followed in the testosterone recovery phase.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
≥ 50 ng/dL	93.01 15%	10.12 3.3%
> 280 ng/dL	53.93 8.7%	3.23 1%
> Baseline level or 280 ng/dL	54.73 8.8%	3.23 1%

10. Secondary Outcome

Title	Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1
Description	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.
Time Frame	Week 5 Day 1 (Day 29) through Week 49 Day 1 (Day 337)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Number (95% Confidence Interval) [percentage of participants]	81.6 13.1%	68.6 22.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Relugolix, Leuprolide Acetate
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	13.0
	Confidence Interval	(2-Sided) 95%; 6.9 to 19.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference= Relugolix - Leuprolide acetate

11. Secondary Outcome

Title	Profound Castration Rate At Week 1 Day 4 (Day 4)
Description	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.
Time Frame	At Week 1 Day 4 (Day 4)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Number (95% Confidence Interval) [percentage of participants]	6.92 1.1%	0.0 0%

12. Secondary Outcome

Title	Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1
Description	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.
Time Frame	Week 25 Day 1 (Day 169) through Week 49 Day 1 (Day 337)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had analyzable data at the specified timepoint.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Number (95% Confidence Interval) [percentage of participants]	84.6 13.6%	87.5 28.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Relugolix, Leuprolide Acetate
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -7.8 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference= Relugolix - Leuprolide acetate

13. Secondary Outcome

Title	Undetectable PSA Rate
Description	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.
Time Frame	Week 25 Day 1 (Day 169)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Number (95% Confidence Interval) [percentage of participants]	20.7 3.3%	20.8 6.8%

14. Secondary Outcome

Title	Rate Of PSA Progression-free Survival
Description	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.
Time Frame	Week 49 Day 1 (Day 337)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Number (95% Confidence Interval) [percentage of participants]	89.31 14.4%	89.50 29.1%

15. Secondary Outcome

Title	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
Description	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).
Time Frame	Baseline, Week 49 Day 1 (Day 337)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had analyzable data at the specified timepoint.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	543	257
Mean (Standard Deviation) [score on a scale]	-3.8 (18.13)	-3.6 (15.70)

16. Secondary Outcome

Title	Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30
Description	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).
Time Frame	Baseline, Week 49 Day 1 (Day 337)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had analyzable data at the specified timepoint.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	543	257
Physical functioning	-4.6 (13.09)	-4.4 (12.29)
Role functioning	-6.2 (19.92)	-5.6 (17.84)
Emotional functioning	0.5 (16.12)	-0.5 (13.23)
Cognitive functioning	-3.7 (16.77)	-3.8 (16.37)
Social functioning	-2.7 (18.31)	-4.0 (18.18)
Fatigue	6.1 (19.46)	7.0 (18.40)
Nausea and vomiting	0.2 (7.12)	0.8 (6.02)
Pain	1.7 (20.19)	4.0 (21.96)
Dyspnoea	5.3 (19.16)	7.9 (20.25)
Insomnia	4.8 (25.88)	4.8 (21.82)
Appetite loss	-0.6 (17.82)	-0.6 (14.86)
Constipation	1.4 (23.26)	3.5 (18.88)
Diarrhoea	2.0 (16.70)	1.4 (19.60)
Financial difficulties	0.2 (18.28)	0.1 (19.21)

17. Secondary Outcome

Title	Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains
Description	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).
Time Frame	Baseline, Week 49 Day 1 (Day 337)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had analyzable data at the specified timepoint.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	537	256
Sexual activity	13.9 (26.51)	10.8 (27.90)
Sexual functioning	-9.0 (23.37)	-10.4 (21.10)
Hormonal treatment-related symptoms	10.6 (12.25)	11.4 (13.30)

18. Secondary Outcome

Title	Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25
Description	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).
Time Frame	Baseline, Week 49 Day 1 (Day 337)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had analyzable data at the specified timepoint.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	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 depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	537	256
Urinary symptoms	1.1 (15.29)	-0.4 (13.78)
Incontinence aid use	1.0 (15.41)	0.0 (19.80)
Bowel symptoms	1.2 (8.92)	2.0 (9.51)

19. Secondary Outcome

Title	Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire (EuroQoL EQ-5D-5L)
Description	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.
Time Frame	Baseline, Week 49 Day 1 (Day 337)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had analyzable data at the specified timepoint.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	549	259
Mean (Standard Deviation) [score on a scale]	-1.5 (14.36)	-2.7 (14.57)

20. Secondary Outcome

Title	Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone
Description	Blood samples were collected from participants for hormonal measurements.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Week 1 Day 4 (Day 4)	-88.25 (20.696)	147.71 (122.735)
Week 5 Day 1 (Day 29)	-94.54 (8.500)	-82.67 (27.146)
Week 25 Day 1 (Day 169)	-93.93 (7.242)	-93.45 (13.202)
Week 49 Day 1 (Day 337)	-91.54 (16.779)	-95.14 (4.507)

21. Secondary Outcome

Title	Percent Change From Baseline In Serum Concentrations Of FSH
Description	Blood samples were collected from participants for hormonal measurements.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Week 1 Day 4 (Day 4)	-62.59 (9.051)	-4.74 (36.121)
Week 5 Day 1 (Day 29)	-90.80 (8.151)	-67.73 (27.311)
Week 25 Day 1 (Day 169)	-86.32 (10.699)	-47.53 (32.560)
Week 49 Day 1 (Day 337)	-79.39 (21.987)	-47.23 (30.112)

22. Secondary Outcome

Title	Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone
Description	Blood samples were collected from participants for hormonal measurements.
Time Frame	Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Week 5 Day 1 (Day 29)	-87.61 (12.225)	-81.95 (23.733)
Week 25 Day 1 (Day 169)	-88.06 (11.810)	-85.45 (32.261)
Week 49 Day 1 (Day 337)	-88.23 (11.235)	-87.56 (12.088)

23. Secondary Outcome

Title	Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin
Description	Blood samples were collected from participants for hormonal measurements.
Time Frame	Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Week 5 Day 1 (Day 29)	1.08 (22.068)	-1.21 (20.430)
Week 25 Day 1 (Day 169)	7.24 (28.265)	3.59 (24.947)
Week 49 Day 1 (Day 337)	6.54 (28.787)	2.59 (27.051)

24. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) Of Relugolix
Description	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.
Time Frame	Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2

Outcome Measure Data

Analysis Population Description

A subset of Japanese participants enrolled in study were included in the PK analysis.

Arm/Group Title	Relugolix Single-Dose	Relugolix Repeat-Dose
Arm/Group Description	Relugolix oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Relugolix 120-mg tablet administered orally once daily for 2 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.
Measure Participants	7	7
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	125 (220)	46.4 (141)

25. Secondary Outcome

Title	Area Under The Concentration-Time Curve (AUC0-τ) Of Relugolix
Description	The AUC0-τ 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.
Time Frame	Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2

Outcome Measure Data

Analysis Population Description

A subset of Japanese participants enrolled in study were included in the PK analysis.

Arm/Group Title	Relugolix Single-Dose	Relugolix Repeat-Dose
Arm/Group Description	Relugolix oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Relugolix 120-mg tablet administered orally once daily for 2 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.
Measure Participants	7	7
Geometric Mean (Geometric Coefficient of Variation) [ng⸳hr/mL]	663 (151)	373 (51)

26. Secondary Outcome

Title	Time To Maximum Observed Plasma Concentration (Tmax) Of Relugolix
Description	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.
Time Frame	Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2

Outcome Measure Data

Analysis Population Description

A subset of Japanese participants enrolled in study were included in the PK analysis.

Arm/Group Title	Relugolix Single-Dose	Relugolix Repeat-Dose
Arm/Group Description	Relugolix oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Relugolix 120-mg tablet administered orally once daily for 2 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.
Measure Participants	7	7
Median (Full Range) [hours]	1.03	0.983

27. Other Pre-specified Outcome

Title	Percentage of Participants Who Experienced Major Adverse Cardiovascular Events (MACE)
Description	MACE were defined as nonfatal myocardial infarction, nonfatal stroke, and death from any cause.
Time Frame	From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Relugolix	Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.	Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection.
Measure Participants	622	308
Number [percentage of participants]	2.9 0.5%	6.2 2%

Adverse Events

Time Frame	Day 1 (after dosing) through up to 52 weeks
Adverse Event Reporting Description	All randomized participants who received at least 1 dose of study drug in the primary analysis part of the study.
Arm/Group Title	Relugolix		Leuprolide Acetate
Arm/Group Description	Relugolix 120-mg tablet administered orally once daily for 48 weeks following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1.		Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan, and Taiwan), every 3 months by subcutaneous injection.
All Cause Mortality
	Relugolix		Leuprolide Acetate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/622 (1.1%)		9/308 (2.9%)
Serious Adverse Events
	Relugolix		Leuprolide Acetate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/622 (12.2%)		47/308 (15.3%)
Blood and lymphatic system disorders
Anaemia	0/622 (0%)		3/308 (1%)
Pancytopenia	0/622 (0%)		1/308 (0.3%)
Cardiac disorders
Acute myocardial infarction	5/622 (0.8%)		1/308 (0.3%)
Atrial fibrillation	2/622 (0.3%)		1/308 (0.3%)
Acute coronary syndrome	1/622 (0.2%)		0/308 (0%)
Acute left ventricular failure	1/622 (0.2%)		1/308 (0.3%)
Aortic valve stenosis	1/622 (0.2%)		0/308 (0%)
Atrioventricular block complete	1/622 (0.2%)		0/308 (0%)
Atrioventricular block second degree	1/622 (0.2%)		0/308 (0%)
Cardiac failure	1/622 (0.2%)		1/308 (0.3%)
Cardiac failure congestive	1/622 (0.2%)		1/308 (0.3%)
Angina unstable	0/622 (0%)		1/308 (0.3%)
Cardiac failure acute	0/622 (0%)		1/308 (0.3%)
Cardio-respiratory arrest	0/622 (0%)		3/308 (1%)
Cardiopulmonary failure	0/622 (0%)		1/308 (0.3%)
Sinus arrest	0/622 (0%)		1/308 (0.3%)
Sinus node dysfunction	0/622 (0%)		1/308 (0.3%)
Ear and labyrinth disorders
Vertigo	1/622 (0.2%)		1/308 (0.3%)
Endocrine disorders
Hypercalcaemia of malignancy	0/622 (0%)		1/308 (0.3%)
Gastrointestinal disorders
Abdominal pain	2/622 (0.3%)		0/308 (0%)
Abdominal incarcerated hernia	1/622 (0.2%)		0/308 (0%)
Gastric ulcer haemorrhage	1/622 (0.2%)		0/308 (0%)
Gastrointestinal haemorrhage	1/622 (0.2%)		0/308 (0%)
Haemorrhoidal haemorrhage	1/622 (0.2%)		0/308 (0%)
Small intestinal obstruction	1/622 (0.2%)		0/308 (0%)
Vomiting	1/622 (0.2%)		0/308 (0%)
Dysphagia	0/622 (0%)		1/308 (0.3%)
Inguinal hernia	0/622 (0%)		2/308 (0.6%)
Lower gastrointestinal haemorrhage	0/622 (0%)		1/308 (0.3%)
General disorders
Chest discomfort	1/622 (0.2%)		0/308 (0%)
Chest pain	1/622 (0.2%)		0/308 (0%)
Gait disturbance	1/622 (0.2%)		0/308 (0%)
Multiple organ dysfunction syndrome	0/622 (0%)		1/308 (0.3%)
Hepatobiliary disorders
Cholecystitis	0/622 (0%)		1/308 (0.3%)
Cholecystitis acute	0/622 (0%)		1/308 (0.3%)
Infections and infestations
Urinary tract infection	3/622 (0.5%)		2/308 (0.6%)
Appendicitis perforated	2/622 (0.3%)		0/308 (0%)
Bronchitis	2/622 (0.3%)		1/308 (0.3%)
Cellulitis	2/622 (0.3%)		0/308 (0%)
Pneumonia	2/622 (0.3%)		1/308 (0.3%)
Endocarditis	1/622 (0.2%)		0/308 (0%)
Gastroenteritis	1/622 (0.2%)		0/308 (0%)
Pyelonephritis acute	1/622 (0.2%)		0/308 (0%)
Septic shock	1/622 (0.2%)		0/308 (0%)
Tooth abscess	1/622 (0.2%)		0/308 (0%)
Upper respiratory tract infection	1/622 (0.2%)		0/308 (0%)
Osteomyelitis	0/622 (0%)		1/308 (0.3%)
Urosepsis	0/622 (0%)		1/308 (0.3%)
Injury, poisoning and procedural complications
Fall	2/622 (0.3%)		0/308 (0%)
Pulmonary contusion	2/622 (0.3%)		0/308 (0%)
Alcohol poisoning	1/622 (0.2%)		0/308 (0%)
Brachial plexus injury	1/622 (0.2%)		0/308 (0%)
Cystitis radiation	1/622 (0.2%)		0/308 (0%)
Femoral neck fracture	1/622 (0.2%)		0/308 (0%)
Hip fracture	1/622 (0.2%)		0/308 (0%)
Rib fracture	1/622 (0.2%)		0/308 (0%)
Road traffic accident	1/622 (0.2%)		0/308 (0%)
Shunt aneurysm	1/622 (0.2%)		0/308 (0%)
Spinal compression fracture	1/622 (0.2%)		0/308 (0%)
Traumatic fracture	1/622 (0.2%)		0/308 (0%)
Ankle fracture	0/622 (0%)		1/308 (0.3%)
Subcutaneous haematoma	0/622 (0%)		1/308 (0.3%)
Investigations
Blood sodium decreased	1/622 (0.2%)		0/308 (0%)
Troponin increased	1/622 (0.2%)		0/308 (0%)
Liver function test abnormal	0/622 (0%)		1/308 (0.3%)
Metabolism and nutrition disorders
Dehydration	1/622 (0.2%)		0/308 (0%)
Diabetes mellitus inadequate control	1/622 (0.2%)		0/308 (0%)
Hyponatraemia	1/622 (0.2%)		0/308 (0%)
Hyperglycaemia	0/622 (0%)		1/308 (0.3%)
Musculoskeletal and connective tissue disorders
Pathological fracture	2/622 (0.3%)		0/308 (0%)
Arthropathy	1/622 (0.2%)		0/308 (0%)
Intervertebral disc compression	1/622 (0.2%)		0/308 (0%)
Osteoarthritis	1/622 (0.2%)		0/308 (0%)
Osteonecrosis	1/622 (0.2%)		0/308 (0%)
Pain in extremity	1/622 (0.2%)		0/308 (0%)
Rhabdomyolysis	0/622 (0%)		1/308 (0.3%)
Spinal pain	0/622 (0%)		1/308 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	2/622 (0.3%)		0/308 (0%)
Metastases to bone	2/622 (0.3%)		1/308 (0.3%)
Prostate cancer	2/622 (0.3%)		0/308 (0%)
Prostate cancer metastatic	2/622 (0.3%)		2/308 (0.6%)
Basal cell carcinoma	1/622 (0.2%)		0/308 (0%)
Bladder transitional cell carcinoma stage II	1/622 (0.2%)		0/308 (0%)
Malignant melanoma in situ	1/622 (0.2%)		0/308 (0%)
Malignant melanoma stage I	1/622 (0.2%)		0/308 (0%)
Metastases to liver	1/622 (0.2%)		0/308 (0%)
Non-small cell lung cancer metastatic	1/622 (0.2%)		0/308 (0%)
Schwannoma	1/622 (0.2%)		0/308 (0%)
Small cell lung cancer metastatic	1/622 (0.2%)		0/308 (0%)
Transitional cell cancer of the renal pelvis and ureter	1/622 (0.2%)		0/308 (0%)
Cancer pain	0/622 (0%)		1/308 (0.3%)
Metastases to spine	0/622 (0%)		1/308 (0.3%)
Transitional cell carcinoma	0/622 (0%)		1/308 (0.3%)
Nervous system disorders
Ischaemic stroke	2/622 (0.3%)		0/308 (0%)
Encephalopathy	1/622 (0.2%)		0/308 (0%)
Haemorrhagic stroke	1/622 (0.2%)		0/308 (0%)
Hemiparesis	1/622 (0.2%)		0/308 (0%)
Lacunar infarction	1/622 (0.2%)		0/308 (0%)
Spinal cord compression	1/622 (0.2%)		0/308 (0%)
Cerebral haemorrhage	0/622 (0%)		2/308 (0.6%)
Cerebrovascular accident	0/622 (0%)		1/308 (0.3%)
Dizziness	0/622 (0%)		1/308 (0.3%)
Haemorrhage intracranial	0/622 (0%)		1/308 (0.3%)
Presyncope	0/622 (0%)		2/308 (0.6%)
Syncope	0/622 (0%)		2/308 (0.6%)
Transient ischaemic attack	0/622 (0%)		3/308 (1%)
Psychiatric disorders
Mental disorder	1/622 (0.2%)		0/308 (0%)
Suicidal ideation	1/622 (0.2%)		0/308 (0%)
Renal and urinary disorders
Acute kidney injury	4/622 (0.6%)		1/308 (0.3%)
Bladder obstruction	2/622 (0.3%)		0/308 (0%)
Bladder neck obstruction	1/622 (0.2%)		0/308 (0%)
Bladder outlet obstruction	1/622 (0.2%)		0/308 (0%)
Calculus bladder	1/622 (0.2%)		1/308 (0.3%)
Chronic kidney disease	1/622 (0.2%)		0/308 (0%)
Lower urinary tract symptoms	1/622 (0.2%)		0/308 (0%)
Renal failure	1/622 (0.2%)		0/308 (0%)
Tubulointerstitial nephritis	1/622 (0.2%)		0/308 (0%)
Urethral stenosis	1/622 (0.2%)		0/308 (0%)
Urinary bladder polyp	1/622 (0.2%)		0/308 (0%)
Urinary retention	1/622 (0.2%)		0/308 (0%)
Haematuria	0/622 (0%)		1/308 (0.3%)
Hydronephrosis	0/622 (0%)		1/308 (0.3%)
Micturition urgency	0/622 (0%)		1/308 (0.3%)
Urinary tract obstruction	0/622 (0%)		1/308 (0.3%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	2/622 (0.3%)		1/308 (0.3%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	2/622 (0.3%)		1/308 (0.3%)
Pneumothorax	1/622 (0.2%)		0/308 (0%)
Acute respiratory failure	0/622 (0%)		1/308 (0.3%)
Epistaxis	0/622 (0%)		1/308 (0.3%)
Pneumonia aspiration	0/622 (0%)		1/308 (0.3%)
Pulmonary embolism	0/622 (0%)		1/308 (0.3%)
Pulmonary oedema	0/622 (0%)		1/308 (0.3%)
Social circumstances
Homicide	0/622 (0%)		1/308 (0.3%)
Vascular disorders
Aortic stenosis	1/622 (0.2%)		1/308 (0.3%)
Aortic aneurysm	0/622 (0%)		1/308 (0.3%)
Deep vein thrombosis	0/622 (0%)		1/308 (0.3%)
Other (Not Including Serious) Adverse Events
	Relugolix		Leuprolide Acetate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	493/622 (79.3%)		239/308 (77.6%)
Gastrointestinal disorders
Constipation	76/622 (12.2%)		30/308 (9.7%)
Diarrhoea	76/622 (12.2%)		21/308 (6.8%)
Nausea	36/622 (5.8%)		13/308 (4.2%)
General disorders
Asthenia	32/622 (5.1%)		21/308 (6.8%)
Fatigue	134/622 (21.5%)		57/308 (18.5%)
Infections and infestations
Nasopharyngitis	59/622 (9.5%)		29/308 (9.4%)
Investigations
Weight increased	49/622 (7.9%)		20/308 (6.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	75/622 (12.1%)		28/308 (9.1%)
Back pain	50/622 (8%)		28/308 (9.1%)
Pain in extremity	32/622 (5.1%)		19/308 (6.2%)
Nervous system disorders
Dizziness	35/622 (5.6%)		17/308 (5.5%)
Headache	35/622 (5.6%)		13/308 (4.2%)
Psychiatric disorders
Insomnia	43/622 (6.9%)		14/308 (4.5%)
Renal and urinary disorders
Nocturia	36/622 (5.8%)		19/308 (6.2%)
Pollakiuria	37/622 (5.9%)		20/308 (6.5%)
Urinary incontinence	30/622 (4.8%)		16/308 (5.2%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	15/622 (2.4%)		16/308 (5.2%)
Vascular disorders
Hot flush	338/622 (54.3%)		159/308 (51.6%)
Hypertension	49/622 (7.9%)		36/308 (11.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.