The Role of Highly Selective Androgen Receptor (AR) Targeted Therapy in Men With Biochemically Relapsed Hormone Sensitive Prostate Cancer

• Sponsor: Aragon Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01790126
• Collaborator: (none)
• Enrollment: 90
• Locations: 5
• Arms: 3
• Actual Duration (Months): 71.9
• Patients Per Site: 18
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The proposed clinical trial will study the effects of 12 months of therapy with ARN-509 alone, or in combination with an LHRH agonist (LHRHa), each compared with LHRHa alone, in men with a rapidly rising serum PSA after prior definitive local therapy for prostate cancer. The endpoints selected reflect measurable short term effects of androgen deprivation therapy (ADT), including quality of life and several metabolic parameters. In addition, the relative effect of each treatment strategy on PSA suppression as well as testosterone recovery (and subsequent PSA progression) after 12 months of therapy will be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: ARN-509; Drug: LHRH Agonist	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Role of Highly Selective Androgen Receptor (AR) Targeted Therapy in Men With Biochemically Relapsed Hormone Sensitive Prostate Cancer
• Actual Study Start Date: Mar 4, 2013
• Actual Primary Completion Date: Mar 1, 2019
• Actual Study Completion Date: Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ARN-509 ARN-509 Tablets, 240 mg/day administered orally	Drug: ARN-509
Active Comparator: LHRH agonist + ARN-509 Choice of LHRHa per investigator discretion/site practice guidelines (e.g, Eligard®, Zoladex®, Lupron Depot®, Trelstar®) and ARN-509 Tablets, 240 mg/day administered orally	Drug: ARN-509; Drug: LHRH Agonist; Other Names: Eligard® Lupron Depot® Zoladex® Trelstar®
Active Comparator: LHRH agonist Choice of LHRHa per investigator discretion/site practice guidelines (e.g., Eligard®, Zoladex®, Lupron Depot®, Trelstar®).	Drug: LHRH Agonist; Other Names: Eligard® Lupron Depot® Zoladex® Trelstar®

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score at 12 Months [Baseline, at 12 months]

   FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the Prostate Cancer Subscale (PCS). The FACT-General (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0-156. Higher scores indicate higher degree of functioning and better quality of life.

Secondary Outcome Measures

1. Change From Baseline in FACT-P Total Score at 3 and 24 Months [Baseline, at 3 and 24 months]

   FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the Prostate Cancer Subscale (PCS). The FACT-General (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0-156. Higher scores indicate higher degree of functioning and better quality of life.

2. Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score at 3, 12 and 24 Months [Baseline, at 3, 12 and 24 months]

   EORTC QLQ-C30 is a 30 items self-reporting questionnaire resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall health related quality of life. Scores are transformed to 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms.

3. Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months [Baseline, at 3, 12 and 24 months]

   EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It Consist of 25 questions distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions on a 4 point scale (1 'Not at all' to 4 'Very much'). All raw domain scores are linearly transformed to a 0-100 scale, with higher scores reflecting either more symptoms (urinary, bowel, hormonal treatment-related symptoms) or higher levels of activity or functioning (sexual).

4. Change From Baseline in Sexual Health Inventory for Men (SHIM) Total Score at 3, 12, 24 Months [Baseline, at 3, 12, 24 months]

   The SHIM is a well validated abridged 5-item of the 15-item International Index of Erectile Function, which has been extensively studied in men with erectile dysfunction due to various etiologies, including prostate cancer-related therapies. It consists of 5 items pertaining to sexual functioning, with scores ranging from 0-5 for most items. The total score is obtained by adding all five item scores, and can range from 5 to 25. Higher scores indicate higher level of sexual function and less erectile dysfunction.

5. Time to Prostate Specific Antigen (PSA) Progression Based on Modified Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria [Up to 24 months]

   PSA progression was defined as a rise to greater than 50 percent (%) of the baseline serum PSA or rise of 2 nanogram per milliliter (ng/mL) or more above the nadir, whichever is higher, confirmed by repeat measurement at least 2 weeks later.

6. Percentage of Participants Without PSA or Radiographic Progression and With Recovery of Serum Testosterone [Up to 24 months]

   Percentage of participants without evidence of PSA or radiographic progression during the 24-month treatment period and with recovery of serum testosterone at 24 months were reported. Testosterone recovery was defined as a serum testosterone greater than (>) 150 nanogram per deciliter (ng/dL). PSA progression was defined as a rise to greater than 50 percent (%) of the baseline serum PSA or rise of 2 nanogram per milliliter (ng/mL) or more above the nadir, whichever is higher, confirmed by repeat measurement at least 2 weeks later. Radiographic progression was defined as the detection of new metastasis on either bone scan or cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging [MRI]).

7. Percentage of Participants With a Serum PSA Less Than 0.2 ng/mL [From 7 to 24 months]

   Percentage of participants with PSA less than (<) 0.2 ng/mL after 7 months of protocol therapy were reported.

8. Change From Baseline in Body Mass Index (BMI) [Baseline, Day 1 (Cycle 1), Day 28 (Cycle 1, 2, 4, 5, 7, 8, 10 and 11), Day 35 (Cycle 3, 6, 9 and 12) and endpoint (up to 24 months)]

   Change from baseline in BMI was reported. BMI was calculated as 'body weight in kg/(height in meters)* (height in meters)'. Endpoint values are from the last measurement within the analysis period.

9. Change From Baseline in Fasting Plasma Glucose [Baseline, Day 35 (Cycle 3, 6, 9 and 12)]

   The change from baseline in fasting plasma glucose levels was analyzed and reported using a mixed-model for repeated measures.

10. Change From Baseline in Glycated Hemoglobin (HbA1C) [Baseline, Day 35 (Cycle 3, 6, 9 and 12)]

    The change from baseline in HbA1C was analyzed and reported using a mixed-model for repeated measures.

11. Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides [Baseline, Day 35 (Cycle 3, 6, 9 and 12)]

    Change from baseline in cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were analyzed and reported using a mixed-model for repeated measures.

12. Change From Baseline in Bone Mineral Density (BMD) [Baseline, Cycle 12 Day 35]

    Change from baseline in BMD was assessed for femoral neck and lumber spine with DEXA scans.

13. Median Time to Serum Testosterone Recovery to Greater Than (>) 50 ng/dL (Non-castrate) and > 150 ng/dL [Month 13 to Month 24]

    The time to serum testosterone recovery to > 50 ng/dL and > 150 ng/dL from Month 13 to Month 24 of protocol therapy was reported.

14. Change From Baseline in Serum Dihydrotestosterone (DHT) Levels [Baseline, Day 35 (Cycle 6 and Cycle 12)]

    Change from baseline in serum DHT levels was reported.

15. Change From Baseline in Estradiol Levels [Baseline, Day 35 (Cycle 6 and Cycle 12)]

    Change from baseline in estradiol levels was reported.

16. Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) [From date of 1st dose of study drug to date of last dose of study drug plus 30 days (up to 6 years)]

    An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. Treatment-emergent adverse events are those that occurred between the date of 1st dose of study drug and date of last dose of study drug plus 30 days.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Histologically proven adenocarcinoma of the prostate

• Rising PSA after prior definitive local therapy (radical prostatectomy, external beam radiation, or brachytherapy) or combination of radical prostatectomy and radiotherapy with curative intent

• PSA doubling time less than or equal to 12 months

• No evidence of metastatic disease on imaging by whole body bone scan and computerized tomography (CT) or Magnetic Resonance Imaging (MRI) of the abdomen/pelvis within 6 weeks prior to randomization

• Minimum PSA 1.0 ng/mL if prior radical prostatectomy +/- adjuvant or salvage radiation; nadir + 2.0 ng/mL if prior RT without prior radical prostatectomy

• Prior androgen deprivation therapy (ADT) allowed if last dose was greater than (>) 6 months prior to randomization

• No prior androgen deprivation therapy (ADT) or anti-androgen for biochemical relapse

• Serum testosterone > 150 ng/dL at study entry

• No history of seizures or medical conditions which may lower seizure threshold

Key Exclusion Criteria:

• Use of 5-alpha reductase antagonist (i.e. finasteride, dutasteride) within 6 weeks prior to randomization

• Use of antiandrogen (e.g. flutamide, nilutamide, bicalutamide) within 6 weeks prior to randomization

• Prior bilateral orchiectomy

• Prior treatment with ADT for biochemically relapsed prostate cancer. Prior ADT as neo-adjuvant, concurrent, and/or adjuvant treatment following salvage radiation therapy or prostatectomy for biochemically relapsed disease is allowed provided last dose of ADT is greater than (>) 6 months prior to randomization and the Screening serum testosterone level is greater than or equal to (≥)150 ng/dL

• Use of systemic steroids at an equivalent dose of prednisone 5 mg/day or higher at randomization

• Any history of seizures or medical condition which lowers seizure threshold

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Scottsdale	Arizona	United States
2		San Francisco	California	United States
3		Chicago	Illinois	United States
4		Portland	Oregon	United States
5		Seattle	Washington	United States

Sponsors and Collaborators

• Aragon Pharmaceuticals, Inc.

Investigators

• Study Director: Aragon Pharmaceuticals, Inc Clinical Trial, Aragon Pharmaceuticals, Inc.

Study Documents (Full-Text)

• Study Protocol - Feb 1, 2019
• Statistical Analysis Plan - Mar 26, 2019

More Information

Publications

None provided.

• Responsible Party: Aragon Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01790126
• Other Study ID Numbers: CR103305; ARN-509-002
• First Posted: Feb 13, 2013
• Last Update Posted: Mar 11, 2020
• Last Verified: Feb 1, 2020

• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Aragon Pharmaceuticals, Inc.: Men with Biochemically Relapsed Hormone Sensitive Prostate Cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Hypersensitivity; Triptorelin Pamoate

Study Results

Participant Flow

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Period Title: Overall Study
STARTED	30	29	31
Treated	29	29	31
COMPLETED	0	0	0
NOT COMPLETED	30	29	31

Baseline Characteristics

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide	Total
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Total of all reporting groups
Overall Participants	30	29	31	90
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	67.3 (6.51)	66.1 (6.18)	67.5 (6.67)	67.0 (6.42)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	30 100%	29 100%	31 100%	90 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	3 10.3%	0 0%	3 3.3%
Not Hispanic or Latino	30 100%	26 89.7%	30 96.8%	86 95.6%
Unknown or Not Reported	0 0%	0 0%	1 3.2%	1 1.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	2 6.7%	1 3.4%	1 3.2%	4 4.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 3.4%	1 3.2%	2 2.2%
White	26 86.7%	26 89.7%	29 93.5%	81 90%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 6.7%	1 3.4%	0 0%	3 3.3%
Region of Enrollment (Count of Participants)
UNITED STATES	30 100%	29 100%	31 100%	90 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score at 12 Months
Description	FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the Prostate Cancer Subscale (PCS). The FACT-General (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0-156. Higher scores indicate higher degree of functioning and better quality of life.
Time Frame	Baseline, at 12 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population included all randomized participants and was classified according to their assigned treatment group, regardless of the actual treatment received.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	30	29	31
Least Squares Mean (Standard Error) [Units on a scale]	-8.04 (2.40)	-6.60 (2.53)	-9.42 (2.30)

2. Secondary Outcome

Title	Change From Baseline in FACT-P Total Score at 3 and 24 Months
Description	FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the Prostate Cancer Subscale (PCS). The FACT-General (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0-156. Higher scores indicate higher degree of functioning and better quality of life.
Time Frame	Baseline, at 3 and 24 months

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants and was classified according to their assigned treatment group, regardless of the actual treatment received.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	30	29	31
Change at 3 months	-2.62 (2.49)	-4.80 (2.45)	-6.72 (2.29)
Change at 24 months	-4.43 (2.91)	1.84 (3.17)	-1.87 (2.59)

3. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score at 3, 12 and 24 Months
Description	EORTC QLQ-C30 is a 30 items self-reporting questionnaire resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall health related quality of life. Scores are transformed to 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms.
Time Frame	Baseline, at 3, 12 and 24 months

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants and was classified according to their assigned treatment group, regardless of the actual treatment received.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	30	29	31
Appetite loss: Change at 3 months	2.80 (2.84)	3.43 (2.75)	8.04 (2.48)
Appetite loss: Change at 12 months	3.49 (3.34)	4.87 (3.51)	5.70 (3.09)
Appetite loss: Change at 24 months	-2.29 (4.05)	-2.50 (4.35)	5.28 (3.29)
Cognitive functioning: Change at 3 months	-2.44 (3.69)	-6.83 (3.62)	-7.73 (3.28)
Cognitive functioning: Change at 12 months	-2.21 (3.40)	-11.50 (3.58)	-8.27 (3.19)
Cognitive functioning: Change at 24 months	-5.08 (4.16)	-12.71 (4.64)	-4.42 (3.55)
Constipation: Change at 3 months	2.90 (3.01)	-3.21 (2.94)	3.45 (2.65)
Constipation: Change at 12 months	10.12 (3.18)	0.27 (3.36)	7.69 (2.96)
Constipation: Change at 24 months	0.45 (4.10)	0.91 (4.43)	-0.10 (3.33)
Diarrhoea: Change at 3 months	5.99 (4.26)	8.10 (4.20)	8.09 (3.77)
Diarrhoea: Change at 12 months	0.02 (3.66)	0.96 (3.87)	3.28 (3.42)
Diarrhoea: Change at 24 months	-0.35 (4.49)	-1.96 (4.97)	4.38 (3.73)
Dyspnoea: Change at 3 months	6.42 (4.36)	13.22 (4.29)	12.85 (3.86)
Dyspnoea: Change at 12 months	4.45 (4.07)	10.32 (4.34)	9.49 (3.82)
Dyspnoea: Change at 24 months	11.16 (5.41)	8.89 (5.86)	7.34 (4.42)
Emotional functioning: Change at 3 months	-0.81 (2.79)	-2.59 (2.73)	1.41 (2.46)
Emotional functioning: Change at 12 months	1.39 (2.46)	1.71 (2.60)	3.84 (2.29)
Emotional functioning: Change at 24 months	-0.60 (3.37)	3.59 (3.67)	3.13 (2.77)
Fatigue: Change at 3 months	11.40 (4.32)	21.85 (4.30)	22.40 (3.80)
Fatigue: Change at 12 months	15.29 (3.97)	13.29 (4.22)	19.80 (3.70)
Fatigue: Change at 24 months	11.33 (4.96)	5.53 (5.49)	5.81 (4.10)
Financial difficulties: Change at 3 months	-5.91 (3.39)	-1.79 (3.33)	2.49 (3.03)
Financial difficulties: Change at 12 months	-6.26 (3.49)	3.98 (3.70)	3.90 (3.28)
Financial difficulties: Change at 24 months	-10.69 (4.47)	-1.56 (4.88)	-3.90 (3.71)
Global health status: Change at 3 months	-3.57 (3.45)	-10.30 (3.36)	-9.19 (3.01)
Global health status: Change at 12 months	-4.90 (3.08)	-8.28 (3.23)	-6.08 (2.85)
Global health status: Change at 24 months	-8.14 (4.14)	-3.73 (4.52)	-7.05 (3.39)
Insomnia: Change at 3 months	6.88 (6.18)	5.31 (6.08)	14.34 (5.46)
Insomnia: Change at 12 months	15.89 (5.46)	2.71 (5.80)	8.60 (5.12)
Insomnia: Change at 24 months	16.34 (6.96)	2.49 (7.83)	-3.00 (5.76)
Nausea and vomiting: Change at 3 months	2.88 (1.56)	3.62 (1.53)	3.99 (1.38)
Nausea and vomiting: Change at 12 months	2.08 (1.34)	2.05 (1.43)	3.51 (1.26)
Nausea and vomiting: Change at 24 months	1.19 (1.19)	0 (0)	1.59 (1.09)
Pain: Change at 3 months	2.57 (4.03)	1.63 (3.95)	3.53 (3.56)
Pain: Change at 12 months	6.24 (3.89)	4.41 (4.11)	14.42 (3.64)
Pain: Change at 24 months	2.84 (4.84)	2.12 (5.21)	2.99 (3.92)
Physical functioning: Change at 3 months	-1.68 (2.51)	-7.72 (2.46)	-3.87 (2.22)
Physical functioning: Change at 12 months	-4.90 (2.45)	-6.32 (2.59)	-6.78 (2.30)
Physical functioning: Change at 24 months	-7.08 (2.96)	-3.61 (3.21)	-3.80 (2.50)
Role functioning: Change at 3 months	-6.92 (3.94)	-4.70 (3.87)	-8.14 (3.48)
Role functioning: Change at 12 months	-6.55 (4.00)	-9.65 (4.24)	-12.12 (3.75)
Role functioning: Change at 24 months	-3.48 (4.99)	0.08 (5.43)	-7.57 (4.06)
Social functioning: Change at 3 months	-5.72 (4.03)	-1.95 (3.96)	-9.57 (3.56)
Social functioning: Change at 12 months	-6.95 (3.69)	-0.37 (3.91)	-5.01 (3.45)
Social functioning: Change at 24 months	5.15 (4.64)	3.90 (5.06)	-2.93 (3.81)

4. Secondary Outcome

Title	Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months
Description	EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It Consist of 25 questions distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions on a 4 point scale (1 'Not at all' to 4 'Very much'). All raw domain scores are linearly transformed to a 0-100 scale, with higher scores reflecting either more symptoms (urinary, bowel, hormonal treatment-related symptoms) or higher levels of activity or functioning (sexual).
Time Frame	Baseline, at 3, 12 and 24 months

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants and was classified according to their assigned treatment group, regardless of the actual treatment received.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	30	29	31
Incontinence aid: Change at 3 months	21.74 (11.72)	3.35 (14.22)	12.09 (10.97)
Incontinence aid: Change at 12 months	14.31 (9.92)	15.11 (10.07)	2.78 (9.44)
Incontinence aid: Change at 24 months	20.60 (16.04)	32.59 (12.52)	19.46 (9.82)
Bowel symptoms: Change at 3 months	1.43 (1.53)	4.27 (1.49)	5.37 (1.33)
Bowel symptoms: Change at 12 months	5.11 (1.57)	1.36 (1.69)	3.76 (1.45)
Bowel symptoms: Change at 24 months	-0.82 (1.98)	0.93 (2.09)	1.48 (1.56)
HTRS: Change at 3 months	10.56 (2.25)	8.09 (2.21)	13.32 (2.01)
HTRS: Change at 12 months	14.72 (2.44)	18.05 (2.59)	19.43 (2.30)
HTRS: Change at 24 months	6.42 (3.16)	1.30 (3.45)	5.39 (2.62)
Sexual activity: Change at 3 months	20.18 (4.40)	16.10 (4.32)	19.78 (3.98)
Sexual activity: Change at 12 months	33.50 (4.03)	19.16 (4.24)	25.02 (3.83)
Sexual activity: Change at 24 months	13.17 (5.23)	11.46 (5.72)	12.56 (4.39)
Sexual functioning: Change at 3 months	9.65 (9.80)	22.03 (9.03)	37.20 (10.73)
Sexual functioning: Change at 12 months	10.65 (10.09)	-1.19 (9.05)	10.73 (11.14)
Sexual functioning: Change at 24 months	-6.41 (12.58)	12.33 (11.54)	0.32 (11.34)
Urinary symptoms: Change at 3 months	8.87 (2.61)	2.55 (2.54)	7.16 (2.28)
Urinary symptoms: Change at 12 months	5.47 (2.45)	1.81 (2.57)	10.54 (2.26)
Urinary symptoms: Change at 24 months	5.87 (3.26)	0.52 (3.50)	9.16 (2.70)

5. Secondary Outcome

Title	Change From Baseline in Sexual Health Inventory for Men (SHIM) Total Score at 3, 12, 24 Months
Description	The SHIM is a well validated abridged 5-item of the 15-item International Index of Erectile Function, which has been extensively studied in men with erectile dysfunction due to various etiologies, including prostate cancer-related therapies. It consists of 5 items pertaining to sexual functioning, with scores ranging from 0-5 for most items. The total score is obtained by adding all five item scores, and can range from 5 to 25. Higher scores indicate higher level of sexual function and less erectile dysfunction.
Time Frame	Baseline, at 3, 12, 24 months

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants and was classified according to their assigned treatment group, regardless of the actual treatment received.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	30	29	31
Change at 3 months	-3.64 (0.74)	-1.80 (0.67)	-3.54 (0.63)
Change at 12 months	-3.52 (0.81)	-2.91 (0.83)	-3.79 (0.78)
Change at 24 months	-1.97 (1.16)	-2.03 (1.17)	-2.39 (0.99)

6. Secondary Outcome

Title	Time to Prostate Specific Antigen (PSA) Progression Based on Modified Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria
Description	PSA progression was defined as a rise to greater than 50 percent (%) of the baseline serum PSA or rise of 2 nanogram per milliliter (ng/mL) or more above the nadir, whichever is higher, confirmed by repeat measurement at least 2 weeks later.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants and was classified according to their assigned treatment group, regardless of the actual treatment received.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	30	29	31
Median (95% Confidence Interval) [Months]	30.88	25.79	36.11

7. Secondary Outcome

Title	Percentage of Participants Without PSA or Radiographic Progression and With Recovery of Serum Testosterone
Description	Percentage of participants without evidence of PSA or radiographic progression during the 24-month treatment period and with recovery of serum testosterone at 24 months were reported. Testosterone recovery was defined as a serum testosterone greater than (>) 150 nanogram per deciliter (ng/dL). PSA progression was defined as a rise to greater than 50 percent (%) of the baseline serum PSA or rise of 2 nanogram per milliliter (ng/mL) or more above the nadir, whichever is higher, confirmed by repeat measurement at least 2 weeks later. Radiographic progression was defined as the detection of new metastasis on either bone scan or cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging [MRI]).
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Modified Intent-to-treat Population (mITT) included subset of ITT population for outcomes related to testosterone recovery, participants who withdrew from the study prior to 24 months after Day 1 were excluded from the analysis. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	26	27	29
Number [Percentage of participants]	19.2 64%	37.0 127.6%	37.9 122.3%

8. Secondary Outcome

Title	Percentage of Participants With a Serum PSA Less Than 0.2 ng/mL
Description	Percentage of participants with PSA less than (<) 0.2 ng/mL after 7 months of protocol therapy were reported.
Time Frame	From 7 to 24 months

Outcome Measure Data

Analysis Population Description

mITT included subset of ITT population for outcomes related to testosterone recovery, participants who withdrew from the study prior to 24 months after Day 1 were excluded from the analysis. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	26	27	29
Number [Percentage of participants]	88.5 295%	88.9 306.6%	96.6 311.6%

9. Secondary Outcome

Title	Change From Baseline in Body Mass Index (BMI)
Description	Change from baseline in BMI was reported. BMI was calculated as 'body weight in kg/(height in meters)* (height in meters)'. Endpoint values are from the last measurement within the analysis period.
Time Frame	Baseline, Day 1 (Cycle 1), Day 28 (Cycle 1, 2, 4, 5, 7, 8, 10 and 11), Day 35 (Cycle 3, 6, 9 and 12) and endpoint (up to 24 months)

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least 1 dose of study drug as actually treated. Here, 'n' (number of participants analyzed) signifies the number of participants analyzed at a specified time point. "Number Analyzed=0" signifies that no participants were evaluated for the specified parameter at that time point.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	29	29	31
Change at Cycle 1 Day 1	0.00	0.00
Change at Cycle 1 Day 28	0.00 (0.443)	-0.02 (0.569)	-0.29 (0.458)
Change at Cycle 2 Day 28	-0.06 (0.903)	-0.23 (0.616)	-0.32 (0.524)
Change at Cycle 3 Day 35	0.02 (0.837)	-0.34 (0.729)	-0.24 (0.610)
Change at Cycle 4 Day 28	0.19 (0.784)	-0.17 (0.710)	-0.12 (0.645)
Change at Cycle 5 Day 28	0.26 (0.892)	-0.15 (0.830)	0.05 (0.716)
Change at Cycle 6 Day 35	0.43 (0.851)	-0.15 (1.041)	-0.01 (0.771)
Change at Cycle 7 Day 28	0.48 (0.862)	-0.16 (1.114)	0.07 (0.743)
Change at Cycle 8 Day 28	0.56 (0.880)	0.02 (1.208)	0.15 (0.811)
Change at Cycle 9 Day 35	0.58 (0.919)	0.04 (1.189)	0.06 (0.822)
Change at Cycle 10 Day 28	0.66 (1.059)	0.12 (1.345)	0.20 (0.584)
Change at Cycle 11 Day 28	0.63 (1.227)	0.04 (1.248)	0.24 (0.825)
Change at Cycle 12 Day 35	0.66 (1.049)	0.01 (1.312)	0.15 (0.682)
Endpoint	0.65 (0.992)	-0.07 (1.272)	0.11 (0.705)

10. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose
Description	The change from baseline in fasting plasma glucose levels was analyzed and reported using a mixed-model for repeated measures.
Time Frame	Baseline, Day 35 (Cycle 3, 6, 9 and 12)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants and was classified according to their assigned treatment group, regardless of the actual treatment received. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	29	29	31
Change at Cycle 3 Day 35	-0.07 (0.24)	0.11 (0.23)	0.61 (0.21)
Change at Cycle 6 Day 35	0.19 (0.19)	-0.00 (0.19)	0.27 (0.17)
Change at Cycle 9 Day 35	0.10 (0.18)	-0.10 (0.19)	0.41 (0.16)
Change at Cycle 12 Day 35	0.29 (0.19)	0.15 (0.19)	0.26 (0.16)

11. Secondary Outcome

Title	Change From Baseline in Glycated Hemoglobin (HbA1C)
Description	The change from baseline in HbA1C was analyzed and reported using a mixed-model for repeated measures.
Time Frame	Baseline, Day 35 (Cycle 3, 6, 9 and 12)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants and was classified according to their assigned treatment group, regardless of the actual treatment received. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	29	29	31
Change at Cycle 3 Day 35	0.14 (0.06)	-0.07 (0.06)	0.06 (0.06)
Change at Cycle 6 Day 35	0.09 (0.06)	-0.10 (0.06)	0.08 (0.06)
Change at Cycle 9 Day 35	0.16 (0.06)	-0.13 (0.06)	0.04 (0.06)
Change at Cycle 12 Day 35	0.18 (0.06)	-0.09 (0.06)	0.13 (0.06)

12. Secondary Outcome

Title	Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides
Description	Change from baseline in cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were analyzed and reported using a mixed-model for repeated measures.
Time Frame	Baseline, Day 35 (Cycle 3, 6, 9 and 12)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants and was classified according to their assigned treatment group, regardless of the actual treatment received. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	29	29	31
Cholesterol: Change at Cycle 3 Day 35	0.34 (0.16)	0.98 (0.16)	1.28 (0.13)
Cholesterol: Change at Cycle 6 Day 35	0.18 (0.16)	0.71 (0.16)	1.35 (0.13)
Cholesterol: Change at Cycle 9 Day 35	0.24 (0.16)	0.66 (0.17)	1.21 (0.14)
Cholesterol: Change at Cycle 12 Day 35	0.38 (0.16)	0.71 (0.17)	0.92 (0.15)
LDL Cholesterol: Change at Cycle 3 Day 35	0.08 (0.15)	0.67 (0.15)	0.91 (0.13)
LDL Cholesterol: Change at Cycle 6 Day 35	-0.03 (0.15)	0.36 (0.15)	0.87 (0.13)
LDL Cholesterol: Change at Cycle 9 Day 35	0.01 (0.14)	0.28 (0.15)	0.69 (0.13)
LDL Cholesterol: Change at Cycle 12 Day 35	0.07 (0.15)	0.31 (0.16)	0.57 (0.13)
HDL Cholesterol: Change at Cycle 3 Day 35	0.08 (0.04)	0.07 (0.05)	0.13 (0.04)
HDL Cholesterol: Change at Cycle 6 Day 35	0.09 (0.04)	0.16 (0.05)	0.12 (0.04)
HDL Cholesterol: Change at Cycle 9 Day 35	0.10 (0.05)	0.21 (0.05)	0.17 (0.04)
HDL Cholesterol: Change at Cycle 12 Day 35	0.12 (0.05)	0.21 (0.06)	0.12 (0.05)
Triglycerides: Change at Cycle 3 Day 35	0.27 (0.14)	0.31 (0.14)	0.34 (0.12)
Triglycerides: Change at Cycle 6 Day 35	0.21 (0.15)	0.14 (0.15)	0.52 (0.13)
Triglycerides: Change at Cycle 9 Day 35	0.30 (0.15)	-0.01 (0.16)	0.53 (0.14)
Triglycerides: Change at Cycle 12 Day 35	0.43 (0.15)	0.08 (0.16)	0.28 (0.13)

13. Secondary Outcome

Title	Change From Baseline in Bone Mineral Density (BMD)
Description	Change from baseline in BMD was assessed for femoral neck and lumber spine with DEXA scans.
Time Frame	Baseline, Cycle 12 Day 35

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants and was classified according to their assigned treatment group, regardless of the actual treatment received. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	29	29	31
Femoral Neck	0.00 (0.03)	0.07 (0.03)	-0.02 (0.02)
Lumbar Spine	0.00 (0.02)	0.01 (0.02)	-0.06 (0.02)

14. Secondary Outcome

Title	Median Time to Serum Testosterone Recovery to Greater Than (>) 50 ng/dL (Non-castrate) and > 150 ng/dL
Description	The time to serum testosterone recovery to > 50 ng/dL and > 150 ng/dL from Month 13 to Month 24 of protocol therapy was reported.
Time Frame	Month 13 to Month 24

Outcome Measure Data

Analysis Population Description

mITT included subset of ITT population for outcomes related to testosterone recovery, participants who withdrew from the study prior to 24 months after Day 1 were excluded from the analysis. This outcome measure was planned to be analyzed and reported for LHRHa-based treatment arms.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	27	30
> 50 ng/dL	18.89	18.10
> 150 ng/dL	23.33	23.98

15. Secondary Outcome

Title	Change From Baseline in Serum Dihydrotestosterone (DHT) Levels
Description	Change from baseline in serum DHT levels was reported.
Time Frame	Baseline, Day 35 (Cycle 6 and Cycle 12)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants and was classified according to their assigned treatment group, regardless of the actual treatment received. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	29	29	31
Change at Cycle 6 Day 35	-0.90 (0.26)	0.93 (0.27)	-0.90 (0.23)
Change at Cycle 12 Day 35	-0.90 (0.24)	0.86 (0.25)	-0.90 (0.21)

16. Secondary Outcome

Title	Change From Baseline in Estradiol Levels
Description	Change from baseline in estradiol levels was reported.
Time Frame	Baseline, Day 35 (Cycle 6 and Cycle 12)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants and was classified according to their assigned treatment group, regardless of the actual treatment received. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	29	29	31
Change at Cycle 6 Day 35	-88.63 (12.24)	87.87 (13.37)	-94.11 (11.58)
Change at Cycle 12 Day 35	-77.12 (13.46)	81.29 (13.88)	-103.01 (12.76)

17. Secondary Outcome

Title	Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
Description	An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. Treatment-emergent adverse events are those that occurred between the date of 1st dose of study drug and date of last dose of study drug plus 30 days.
Time Frame	From date of 1st dose of study drug to date of last dose of study drug plus 30 days (up to 6 years)

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least 1 dose of study drug as actually treated.

Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)	Apalutamide	LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
Measure Participants	29	29	31
Number [Percentage of participants]	96.6 322%	100.0 344.8%	100.0 322.6%

Adverse Events

Time Frame	Up to 6 years
Adverse Event Reporting Description	The safety population included all participants who received at least 1 dose of study drug as actually treated.
Arm/Group Title	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)		Apalutamide		LHRHa + Apalutamide
Arm/Group Description	Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines up to 12 months, or shorter duration if evidence of prostate-specific antigen (PSA)/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study.		Participants received apalutamide, 240 milligram (mg) soft-gel capsules (8*30 mg capsules) per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).		Participants received LHRHa injections either subcutaneously or intramuscularly as per investigator discretion/site practice guidelines and apalutamide 240 mg soft-gel capsules per day orally up to 12 months, or shorter duration if evidence of PSA/radiographic progression or unacceptable toxicity during protocol therapy or participant/physician withdrawal from the study. With Amendment 7, participants who were receiving the apalutamide soft-gel capsules were switched to the apalutamide tablet formulation (4*60 mg tablets).
All Cause Mortality
	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)		Apalutamide		LHRHa + Apalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)		0/29 (0%)		0/31 (0%)
Serious Adverse Events
	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)		Apalutamide		LHRHa + Apalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/29 (10.3%)		0/29 (0%)		5/31 (16.1%)
Cardiac disorders
Acute Myocardial Infarction	0/29 (0%)		0/29 (0%)		1/31 (3.2%)
Angina Pectoris	0/29 (0%)		0/29 (0%)		1/31 (3.2%)
Atrial Fibrillation	0/29 (0%)		0/29 (0%)		1/31 (3.2%)
Ventricular Tachycardia	1/29 (3.4%)		0/29 (0%)		0/31 (0%)
Ear and labyrinth disorders
Vertigo	1/29 (3.4%)		0/29 (0%)		0/31 (0%)
Infections and infestations
Wound Infection	0/29 (0%)		0/29 (0%)		1/31 (3.2%)
Injury, poisoning and procedural complications
Rib Fracture	0/29 (0%)		0/29 (0%)		1/31 (3.2%)
Nervous system disorders
Transient Ischaemic Attack	0/29 (0%)		0/29 (0%)		1/31 (3.2%)
Product Issues
Device Failure	1/29 (3.4%)		0/29 (0%)		0/31 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	0/29 (0%)		0/29 (0%)		1/31 (3.2%)
Skin and subcutaneous tissue disorders
Angioedema	0/29 (0%)		0/29 (0%)		1/31 (3.2%)
Toxic Epidermal Necrolysis	1/29 (3.4%)		0/29 (0%)		0/31 (0%)
Vascular disorders
Hypertension	0/29 (0%)		0/29 (0%)		1/31 (3.2%)
Other (Not Including Serious) Adverse Events
	Luteinizing Hormone Releasing Hormone Agonist (LHRHa)		Apalutamide		LHRHa + Apalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/29 (96.6%)		29/29 (100%)		30/31 (96.8%)
Blood and lymphatic system disorders
Anaemia	4/29 (13.8%)		0/29 (0%)		0/31 (0%)
Cardiac disorders
Angina Pectoris	1/29 (3.4%)		0/29 (0%)		2/31 (6.5%)
Ear and labyrinth disorders
Tinnitus	1/29 (3.4%)		3/29 (10.3%)		0/31 (0%)
Endocrine disorders
Hypothyroidism	0/29 (0%)		1/29 (3.4%)		2/31 (6.5%)
Eye disorders
Eyelid Ptosis	0/29 (0%)		2/29 (6.9%)		0/31 (0%)
Gastrointestinal disorders
Abdominal Discomfort	0/29 (0%)		5/29 (17.2%)		2/31 (6.5%)
Abdominal Pain	1/29 (3.4%)		3/29 (10.3%)		4/31 (12.9%)
Constipation	2/29 (6.9%)		2/29 (6.9%)		3/31 (9.7%)
Diarrhoea	0/29 (0%)		7/29 (24.1%)		4/31 (12.9%)
Dyspepsia	0/29 (0%)		3/29 (10.3%)		2/31 (6.5%)
Flatulence	0/29 (0%)		4/29 (13.8%)		3/31 (9.7%)
Gastrooesophageal Reflux Disease	0/29 (0%)		1/29 (3.4%)		2/31 (6.5%)
Nausea	2/29 (6.9%)		4/29 (13.8%)		7/31 (22.6%)
Vomiting	1/29 (3.4%)		1/29 (3.4%)		3/31 (9.7%)
General disorders
Asthenia	0/29 (0%)		0/29 (0%)		2/31 (6.5%)
Fatigue	22/29 (75.9%)		19/29 (65.5%)		24/31 (77.4%)
Oedema Peripheral	0/29 (0%)		1/29 (3.4%)		3/31 (9.7%)
Infections and infestations
Bronchitis	0/29 (0%)		0/29 (0%)		2/31 (6.5%)
Conjunctivitis	0/29 (0%)		2/29 (6.9%)		0/31 (0%)
Upper Respiratory Tract Infection	1/29 (3.4%)		3/29 (10.3%)		4/31 (12.9%)
Injury, poisoning and procedural complications
Fall	2/29 (6.9%)		1/29 (3.4%)		4/31 (12.9%)
Investigations
Aspartate Aminotransferase Increased	2/29 (6.9%)		0/29 (0%)		0/31 (0%)
Heart Rate Irregular	0/29 (0%)		2/29 (6.9%)		0/31 (0%)
Weight Decreased	0/29 (0%)		1/29 (3.4%)		2/31 (6.5%)
Weight Increased	3/29 (10.3%)		2/29 (6.9%)		3/31 (9.7%)
Metabolism and nutrition disorders
Decreased Appetite	1/29 (3.4%)		2/29 (6.9%)		4/31 (12.9%)
Hypercholesterolaemia	3/29 (10.3%)		4/29 (13.8%)		6/31 (19.4%)
Hypertriglyceridaemia	1/29 (3.4%)		1/29 (3.4%)		3/31 (9.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/29 (17.2%)		8/29 (27.6%)		7/31 (22.6%)
Back Pain	1/29 (3.4%)		1/29 (3.4%)		6/31 (19.4%)
Muscle Atrophy	2/29 (6.9%)		1/29 (3.4%)		0/31 (0%)
Muscle Spasms	2/29 (6.9%)		1/29 (3.4%)		1/31 (3.2%)
Muscular Weakness	2/29 (6.9%)		2/29 (6.9%)		4/31 (12.9%)
Musculoskeletal Pain	2/29 (6.9%)		2/29 (6.9%)		2/31 (6.5%)
Osteopenia	2/29 (6.9%)		0/29 (0%)		0/31 (0%)
Pain in Extremity	0/29 (0%)		1/29 (3.4%)		6/31 (19.4%)
Spinal Pain	0/29 (0%)		0/29 (0%)		2/31 (6.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma	0/29 (0%)		0/29 (0%)		2/31 (6.5%)
Nervous system disorders
Cognitive Disorder	0/29 (0%)		1/29 (3.4%)		3/31 (9.7%)
Dizziness	1/29 (3.4%)		4/29 (13.8%)		4/31 (12.9%)
Dysgeusia	0/29 (0%)		6/29 (20.7%)		5/31 (16.1%)
Headache	0/29 (0%)		2/29 (6.9%)		6/31 (19.4%)
Memory Impairment	0/29 (0%)		2/29 (6.9%)		3/31 (9.7%)
Paraesthesia	0/29 (0%)		0/29 (0%)		2/31 (6.5%)
Psychiatric disorders
Anxiety	0/29 (0%)		2/29 (6.9%)		1/31 (3.2%)
Depression	1/29 (3.4%)		3/29 (10.3%)		4/31 (12.9%)
Insomnia	2/29 (6.9%)		1/29 (3.4%)		10/31 (32.3%)
Irritability	2/29 (6.9%)		0/29 (0%)		0/31 (0%)
Libido Decreased	3/29 (10.3%)		1/29 (3.4%)		3/31 (9.7%)
Loss of Libido	2/29 (6.9%)		0/29 (0%)		0/31 (0%)
Renal and urinary disorders
Haematuria	3/29 (10.3%)		1/29 (3.4%)		1/31 (3.2%)
Incontinence	0/29 (0%)		0/29 (0%)		2/31 (6.5%)
Reproductive system and breast disorders
Breast Tenderness	0/29 (0%)		4/29 (13.8%)		2/31 (6.5%)
Erectile Dysfunction	1/29 (3.4%)		3/29 (10.3%)		1/31 (3.2%)
Gynaecomastia	3/29 (10.3%)		12/29 (41.4%)		1/31 (3.2%)
Nipple Pain	0/29 (0%)		12/29 (41.4%)		0/31 (0%)
Testicular Pain	2/29 (6.9%)		1/29 (3.4%)		1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
Cough	2/29 (6.9%)		2/29 (6.9%)		2/31 (6.5%)
Dysphonia	0/29 (0%)		2/29 (6.9%)		0/31 (0%)
Dyspnoea	2/29 (6.9%)		2/29 (6.9%)		3/31 (9.7%)
Dyspnoea Exertional	0/29 (0%)		2/29 (6.9%)		1/31 (3.2%)
Rhinorrhoea	0/29 (0%)		1/29 (3.4%)		2/31 (6.5%)
Skin and subcutaneous tissue disorders
Alopecia	0/29 (0%)		4/29 (13.8%)		3/31 (9.7%)
Hypotrichosis	0/29 (0%)		0/29 (0%)		2/31 (6.5%)
Pruritus	0/29 (0%)		2/29 (6.9%)		2/31 (6.5%)
Rash	1/29 (3.4%)		5/29 (17.2%)		5/31 (16.1%)
Rash Maculo-Papular	0/29 (0%)		3/29 (10.3%)		0/31 (0%)
Rash Pruritic	1/29 (3.4%)		2/29 (6.9%)		1/31 (3.2%)
Vascular disorders
Hot Flush	25/29 (86.2%)		9/29 (31%)		26/31 (83.9%)
Hypertension	0/29 (0%)		1/29 (3.4%)		6/31 (19.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.