Trial Outcomes & Findings for The Role of Highly Selective Androgen Receptor (AR) Targeted Therapy in Men With Biochemically Relapsed Hormone Sensitive Prostate Cancer (NCT NCT01790126)

Last Updated: 2020-03-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

90 participants

Primary outcome timeframe

Baseline, at 12 months

Results posted on

2020-03-11

Participant Flow

Participant milestones

Participant milestones
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) 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.	Apalutamide 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).	LHRHa + Apalutamide 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).
Overall Study STARTED	30	29	31
Overall Study Treated	29	29	31
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	30	29	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) 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.	Apalutamide 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).	LHRHa + Apalutamide 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).
Overall Study PSA Progression	12	16	16
Overall Study Other	5	4	8
Overall Study Initiation of Non-Protocol Therapy	3	4	2
Overall Study Withdrawal by Physician	1	1	2
Overall Study Withdrawal by Subject	3	1	2
Overall Study Lost to Follow-up	1	0	1
Overall Study Adverse Event	0	2	0
Overall Study Death	2	0	0
Overall Study Radiographic Progression	3	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=30 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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 n=90 Participants Total of all reporting groups
Age, Continuous	67.3 Years STANDARD_DEVIATION 6.51 • n=93 Participants	66.1 Years STANDARD_DEVIATION 6.18 • n=4 Participants	67.5 Years STANDARD_DEVIATION 6.67 • n=27 Participants	67.0 Years STANDARD_DEVIATION 6.42 • n=483 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Sex: Female, Male Male	30 Participants n=93 Participants	29 Participants n=4 Participants	31 Participants n=27 Participants	90 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	3 Participants n=4 Participants	0 Participants n=27 Participants	3 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	30 Participants n=93 Participants	26 Participants n=4 Participants	30 Participants n=27 Participants	86 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	2 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	4 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants
Race (NIH/OMB) White	26 Participants n=93 Participants	26 Participants n=4 Participants	29 Participants n=27 Participants	81 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	3 Participants n=483 Participants
Region of Enrollment UNITED STATES	30 Participants n=93 Participants	29 Participants n=4 Participants	31 Participants n=27 Participants	90 Participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline, at 12 months

Population: 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.

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=30 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score at 12 Months	-8.04 Units on a scale Standard Error 2.40	-6.60 Units on a scale Standard Error 2.53	-9.42 Units on a scale Standard Error 2.30

SECONDARY outcome

Timeframe: Baseline, at 3 and 24 months

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

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=30 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
Change From Baseline in FACT-P Total Score at 3 and 24 Months Change at 3 months	-2.62 Units on a scale Standard Error 2.49	-4.80 Units on a scale Standard Error 2.45	-6.72 Units on a scale Standard Error 2.29
Change From Baseline in FACT-P Total Score at 3 and 24 Months Change at 24 months	-4.43 Units on a scale Standard Error 2.91	1.84 Units on a scale Standard Error 3.17	-1.87 Units on a scale Standard Error 2.59

SECONDARY outcome

Timeframe: Baseline, at 3, 12 and 24 months

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

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.

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=30 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
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 Cognitive functioning: Change at 12 months	-2.21 Units on a scale Standard Error 3.40	-11.50 Units on a scale Standard Error 3.58	-8.27 Units on a scale Standard Error 3.19
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 Constipation: Change at 3 months	2.90 Units on a scale Standard Error 3.01	-3.21 Units on a scale Standard Error 2.94	3.45 Units on a scale Standard Error 2.65
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 Constipation: Change at 12 months	10.12 Units on a scale Standard Error 3.18	0.27 Units on a scale Standard Error 3.36	7.69 Units on a scale Standard Error 2.96
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 Diarrhoea: Change at 3 months	5.99 Units on a scale Standard Error 4.26	8.10 Units on a scale Standard Error 4.20	8.09 Units on a scale Standard Error 3.77
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 Emotional functioning: Change at 12 months	1.39 Units on a scale Standard Error 2.46	1.71 Units on a scale Standard Error 2.60	3.84 Units on a scale Standard Error 2.29
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 Fatigue: Change at 24 months	11.33 Units on a scale Standard Error 4.96	5.53 Units on a scale Standard Error 5.49	5.81 Units on a scale Standard Error 4.10
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 Financial difficulties: Change at 3 months	-5.91 Units on a scale Standard Error 3.39	-1.79 Units on a scale Standard Error 3.33	2.49 Units on a scale Standard Error 3.03
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 Global health status: Change at 24 months	-8.14 Units on a scale Standard Error 4.14	-3.73 Units on a scale Standard Error 4.52	-7.05 Units on a scale Standard Error 3.39
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 Insomnia: Change at 3 months	6.88 Units on a scale Standard Error 6.18	5.31 Units on a scale Standard Error 6.08	14.34 Units on a scale Standard Error 5.46
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 Social functioning: Change at 3 months	-5.72 Units on a scale Standard Error 4.03	-1.95 Units on a scale Standard Error 3.96	-9.57 Units on a scale Standard Error 3.56
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 Appetite loss: Change at 3 months	2.80 Units on a scale Standard Error 2.84	3.43 Units on a scale Standard Error 2.75	8.04 Units on a scale Standard Error 2.48
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 Social functioning: Change at 24 months	5.15 Units on a scale Standard Error 4.64	3.90 Units on a scale Standard Error 5.06	-2.93 Units on a scale Standard Error 3.81
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 Appetite loss: Change at 12 months	3.49 Units on a scale Standard Error 3.34	4.87 Units on a scale Standard Error 3.51	5.70 Units on a scale Standard Error 3.09
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 Appetite loss: Change at 24 months	-2.29 Units on a scale Standard Error 4.05	-2.50 Units on a scale Standard Error 4.35	5.28 Units on a scale Standard Error 3.29
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 Cognitive functioning: Change at 3 months	-2.44 Units on a scale Standard Error 3.69	-6.83 Units on a scale Standard Error 3.62	-7.73 Units on a scale Standard Error 3.28
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 Cognitive functioning: Change at 24 months	-5.08 Units on a scale Standard Error 4.16	-12.71 Units on a scale Standard Error 4.64	-4.42 Units on a scale Standard Error 3.55
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 Constipation: Change at 24 months	0.45 Units on a scale Standard Error 4.10	0.91 Units on a scale Standard Error 4.43	-0.10 Units on a scale Standard Error 3.33
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 Diarrhoea: Change at 12 months	0.02 Units on a scale Standard Error 3.66	0.96 Units on a scale Standard Error 3.87	3.28 Units on a scale Standard Error 3.42
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 Diarrhoea: Change at 24 months	-0.35 Units on a scale Standard Error 4.49	-1.96 Units on a scale Standard Error 4.97	4.38 Units on a scale Standard Error 3.73
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 Dyspnoea: Change at 3 months	6.42 Units on a scale Standard Error 4.36	13.22 Units on a scale Standard Error 4.29	12.85 Units on a scale Standard Error 3.86
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 Dyspnoea: Change at 12 months	4.45 Units on a scale Standard Error 4.07	10.32 Units on a scale Standard Error 4.34	9.49 Units on a scale Standard Error 3.82
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 Dyspnoea: Change at 24 months	11.16 Units on a scale Standard Error 5.41	8.89 Units on a scale Standard Error 5.86	7.34 Units on a scale Standard Error 4.42
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 Emotional functioning: Change at 3 months	-0.81 Units on a scale Standard Error 2.79	-2.59 Units on a scale Standard Error 2.73	1.41 Units on a scale Standard Error 2.46
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 Emotional functioning: Change at 24 months	-0.60 Units on a scale Standard Error 3.37	3.59 Units on a scale Standard Error 3.67	3.13 Units on a scale Standard Error 2.77
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 Fatigue: Change at 3 months	11.40 Units on a scale Standard Error 4.32	21.85 Units on a scale Standard Error 4.30	22.40 Units on a scale Standard Error 3.80
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 Fatigue: Change at 12 months	15.29 Units on a scale Standard Error 3.97	13.29 Units on a scale Standard Error 4.22	19.80 Units on a scale Standard Error 3.70
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 Financial difficulties: Change at 12 months	-6.26 Units on a scale Standard Error 3.49	3.98 Units on a scale Standard Error 3.70	3.90 Units on a scale Standard Error 3.28
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 Financial difficulties: Change at 24 months	-10.69 Units on a scale Standard Error 4.47	-1.56 Units on a scale Standard Error 4.88	-3.90 Units on a scale Standard Error 3.71
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 Global health status: Change at 3 months	-3.57 Units on a scale Standard Error 3.45	-10.30 Units on a scale Standard Error 3.36	-9.19 Units on a scale Standard Error 3.01
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 Global health status: Change at 12 months	-4.90 Units on a scale Standard Error 3.08	-8.28 Units on a scale Standard Error 3.23	-6.08 Units on a scale Standard Error 2.85
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 Insomnia: Change at 12 months	15.89 Units on a scale Standard Error 5.46	2.71 Units on a scale Standard Error 5.80	8.60 Units on a scale Standard Error 5.12
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 Insomnia: Change at 24 months	16.34 Units on a scale Standard Error 6.96	2.49 Units on a scale Standard Error 7.83	-3.00 Units on a scale Standard Error 5.76
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 Nausea and vomiting: Change at 3 months	2.88 Units on a scale Standard Error 1.56	3.62 Units on a scale Standard Error 1.53	3.99 Units on a scale Standard Error 1.38
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 Nausea and vomiting: Change at 12 months	2.08 Units on a scale Standard Error 1.34	2.05 Units on a scale Standard Error 1.43	3.51 Units on a scale Standard Error 1.26
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 Nausea and vomiting: Change at 24 months	1.19 Units on a scale Standard Error 1.19	0 Units on a scale Standard Error 0	1.59 Units on a scale Standard Error 1.09
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 Pain: Change at 3 months	2.57 Units on a scale Standard Error 4.03	1.63 Units on a scale Standard Error 3.95	3.53 Units on a scale Standard Error 3.56
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 Pain: Change at 12 months	6.24 Units on a scale Standard Error 3.89	4.41 Units on a scale Standard Error 4.11	14.42 Units on a scale Standard Error 3.64
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 Pain: Change at 24 months	2.84 Units on a scale Standard Error 4.84	2.12 Units on a scale Standard Error 5.21	2.99 Units on a scale Standard Error 3.92
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 Physical functioning: Change at 3 months	-1.68 Units on a scale Standard Error 2.51	-7.72 Units on a scale Standard Error 2.46	-3.87 Units on a scale Standard Error 2.22
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 Physical functioning: Change at 12 months	-4.90 Units on a scale Standard Error 2.45	-6.32 Units on a scale Standard Error 2.59	-6.78 Units on a scale Standard Error 2.30
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 Physical functioning: Change at 24 months	-7.08 Units on a scale Standard Error 2.96	-3.61 Units on a scale Standard Error 3.21	-3.80 Units on a scale Standard Error 2.50
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 Role functioning: Change at 3 months	-6.92 Units on a scale Standard Error 3.94	-4.70 Units on a scale Standard Error 3.87	-8.14 Units on a scale Standard Error 3.48
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 Role functioning: Change at 12 months	-6.55 Units on a scale Standard Error 4.00	-9.65 Units on a scale Standard Error 4.24	-12.12 Units on a scale Standard Error 3.75
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 Role functioning: Change at 24 months	-3.48 Units on a scale Standard Error 4.99	0.08 Units on a scale Standard Error 5.43	-7.57 Units on a scale Standard Error 4.06
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 Social functioning: Change at 12 months	-6.95 Units on a scale Standard Error 3.69	-0.37 Units on a scale Standard Error 3.91	-5.01 Units on a scale Standard Error 3.45

SECONDARY outcome

Timeframe: Baseline, at 3, 12 and 24 months

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

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).

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=30 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Incontinence aid: Change at 3 months	21.74 Units on a scale Standard Error 11.72	3.35 Units on a scale Standard Error 14.22	12.09 Units on a scale Standard Error 10.97
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Incontinence aid: Change at 12 months	14.31 Units on a scale Standard Error 9.92	15.11 Units on a scale Standard Error 10.07	2.78 Units on a scale Standard Error 9.44
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Incontinence aid: Change at 24 months	20.60 Units on a scale Standard Error 16.04	32.59 Units on a scale Standard Error 12.52	19.46 Units on a scale Standard Error 9.82
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Bowel symptoms: Change at 3 months	1.43 Units on a scale Standard Error 1.53	4.27 Units on a scale Standard Error 1.49	5.37 Units on a scale Standard Error 1.33
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Bowel symptoms: Change at 12 months	5.11 Units on a scale Standard Error 1.57	1.36 Units on a scale Standard Error 1.69	3.76 Units on a scale Standard Error 1.45
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Bowel symptoms: Change at 24 months	-0.82 Units on a scale Standard Error 1.98	0.93 Units on a scale Standard Error 2.09	1.48 Units on a scale Standard Error 1.56
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months HTRS: Change at 3 months	10.56 Units on a scale Standard Error 2.25	8.09 Units on a scale Standard Error 2.21	13.32 Units on a scale Standard Error 2.01
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months HTRS: Change at 12 months	14.72 Units on a scale Standard Error 2.44	18.05 Units on a scale Standard Error 2.59	19.43 Units on a scale Standard Error 2.30
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months HTRS: Change at 24 months	6.42 Units on a scale Standard Error 3.16	1.30 Units on a scale Standard Error 3.45	5.39 Units on a scale Standard Error 2.62
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Sexual activity: Change at 3 months	20.18 Units on a scale Standard Error 4.40	16.10 Units on a scale Standard Error 4.32	19.78 Units on a scale Standard Error 3.98
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Sexual activity: Change at 12 months	33.50 Units on a scale Standard Error 4.03	19.16 Units on a scale Standard Error 4.24	25.02 Units on a scale Standard Error 3.83
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Sexual activity: Change at 24 months	13.17 Units on a scale Standard Error 5.23	11.46 Units on a scale Standard Error 5.72	12.56 Units on a scale Standard Error 4.39
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Sexual functioning: Change at 3 months	9.65 Units on a scale Standard Error 9.80	22.03 Units on a scale Standard Error 9.03	37.20 Units on a scale Standard Error 10.73
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Sexual functioning: Change at 12 months	10.65 Units on a scale Standard Error 10.09	-1.19 Units on a scale Standard Error 9.05	10.73 Units on a scale Standard Error 11.14
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Sexual functioning: Change at 24 months	-6.41 Units on a scale Standard Error 12.58	12.33 Units on a scale Standard Error 11.54	0.32 Units on a scale Standard Error 11.34
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Urinary symptoms: Change at 3 months	8.87 Units on a scale Standard Error 2.61	2.55 Units on a scale Standard Error 2.54	7.16 Units on a scale Standard Error 2.28
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Urinary symptoms: Change at 12 months	5.47 Units on a scale Standard Error 2.45	1.81 Units on a scale Standard Error 2.57	10.54 Units on a scale Standard Error 2.26
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Urinary symptoms: Change at 24 months	5.87 Units on a scale Standard Error 3.26	0.52 Units on a scale Standard Error 3.50	9.16 Units on a scale Standard Error 2.70

SECONDARY outcome

Timeframe: Baseline, at 3, 12, 24 months

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

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.

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=30 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
Change From Baseline in Sexual Health Inventory for Men (SHIM) Total Score at 3, 12, 24 Months Change at 3 months	-3.64 Units on a scale Standard Error 0.74	-1.80 Units on a scale Standard Error 0.67	-3.54 Units on a scale Standard Error 0.63
Change From Baseline in Sexual Health Inventory for Men (SHIM) Total Score at 3, 12, 24 Months Change at 12 months	-3.52 Units on a scale Standard Error 0.81	-2.91 Units on a scale Standard Error 0.83	-3.79 Units on a scale Standard Error 0.78
Change From Baseline in Sexual Health Inventory for Men (SHIM) Total Score at 3, 12, 24 Months Change at 24 months	-1.97 Units on a scale Standard Error 1.16	-2.03 Units on a scale Standard Error 1.17	-2.39 Units on a scale Standard Error 0.99

SECONDARY outcome

Timeframe: Up to 24 months

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

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.

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=30 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
Time to Prostate Specific Antigen (PSA) Progression Based on Modified Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria	30.88 Months Interval 22.54 to Here, NA indicates upper limit of 95% confidence interval (CI) was not estimable due to insufficient number of events.	25.79 Months Interval 20.04 to 38.9	36.11 Months Interval 26.97 to 56.64

SECONDARY outcome

Timeframe: Up to 24 months

Population: 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.

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 \[MRI\]).

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=26 Participants 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.	Apalutamide n=27 Participants 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).	LHRHa + Apalutamide n=29 Participants 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).
Percentage of Participants Without PSA or Radiographic Progression and With Recovery of Serum Testosterone	19.2 Percentage of participants	37.0 Percentage of participants	37.9 Percentage of participants

SECONDARY outcome

Timeframe: From 7 to 24 months

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.

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

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=26 Participants 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.	Apalutamide n=27 Participants 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).	LHRHa + Apalutamide n=29 Participants 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).
Percentage of Participants With a Serum PSA Less Than 0.2 ng/mL	88.5 Percentage of participants	88.9 Percentage of participants	96.6 Percentage of participants

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=29 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
Change From Baseline in Body Mass Index (BMI) Change at Cycle 1 Day 1	0.00 Kilogram per meter square (kg/m^2)	—	0.00 Kilogram per meter square (kg/m^2)
Change From Baseline in Body Mass Index (BMI) Change at Cycle 1 Day 28	0.00 Kilogram per meter square (kg/m^2) Standard Deviation 0.443	-0.02 Kilogram per meter square (kg/m^2) Standard Deviation 0.569	-0.29 Kilogram per meter square (kg/m^2) Standard Deviation 0.458
Change From Baseline in Body Mass Index (BMI) Change at Cycle 2 Day 28	-0.06 Kilogram per meter square (kg/m^2) Standard Deviation 0.903	-0.23 Kilogram per meter square (kg/m^2) Standard Deviation 0.616	-0.32 Kilogram per meter square (kg/m^2) Standard Deviation 0.524
Change From Baseline in Body Mass Index (BMI) Change at Cycle 3 Day 35	0.02 Kilogram per meter square (kg/m^2) Standard Deviation 0.837	-0.34 Kilogram per meter square (kg/m^2) Standard Deviation 0.729	-0.24 Kilogram per meter square (kg/m^2) Standard Deviation 0.610
Change From Baseline in Body Mass Index (BMI) Change at Cycle 4 Day 28	0.19 Kilogram per meter square (kg/m^2) Standard Deviation 0.784	-0.17 Kilogram per meter square (kg/m^2) Standard Deviation 0.710	-0.12 Kilogram per meter square (kg/m^2) Standard Deviation 0.645
Change From Baseline in Body Mass Index (BMI) Change at Cycle 5 Day 28	0.26 Kilogram per meter square (kg/m^2) Standard Deviation 0.892	-0.15 Kilogram per meter square (kg/m^2) Standard Deviation 0.830	0.05 Kilogram per meter square (kg/m^2) Standard Deviation 0.716
Change From Baseline in Body Mass Index (BMI) Change at Cycle 6 Day 35	0.43 Kilogram per meter square (kg/m^2) Standard Deviation 0.851	-0.15 Kilogram per meter square (kg/m^2) Standard Deviation 1.041	-0.01 Kilogram per meter square (kg/m^2) Standard Deviation 0.771
Change From Baseline in Body Mass Index (BMI) Change at Cycle 7 Day 28	0.48 Kilogram per meter square (kg/m^2) Standard Deviation 0.862	-0.16 Kilogram per meter square (kg/m^2) Standard Deviation 1.114	0.07 Kilogram per meter square (kg/m^2) Standard Deviation 0.743
Change From Baseline in Body Mass Index (BMI) Change at Cycle 8 Day 28	0.56 Kilogram per meter square (kg/m^2) Standard Deviation 0.880	0.02 Kilogram per meter square (kg/m^2) Standard Deviation 1.208	0.15 Kilogram per meter square (kg/m^2) Standard Deviation 0.811
Change From Baseline in Body Mass Index (BMI) Change at Cycle 9 Day 35	0.58 Kilogram per meter square (kg/m^2) Standard Deviation 0.919	0.04 Kilogram per meter square (kg/m^2) Standard Deviation 1.189	0.06 Kilogram per meter square (kg/m^2) Standard Deviation 0.822
Change From Baseline in Body Mass Index (BMI) Change at Cycle 10 Day 28	0.66 Kilogram per meter square (kg/m^2) Standard Deviation 1.059	0.12 Kilogram per meter square (kg/m^2) Standard Deviation 1.345	0.20 Kilogram per meter square (kg/m^2) Standard Deviation 0.584
Change From Baseline in Body Mass Index (BMI) Change at Cycle 11 Day 28	0.63 Kilogram per meter square (kg/m^2) Standard Deviation 1.227	0.04 Kilogram per meter square (kg/m^2) Standard Deviation 1.248	0.24 Kilogram per meter square (kg/m^2) Standard Deviation 0.825
Change From Baseline in Body Mass Index (BMI) Change at Cycle 12 Day 35	0.66 Kilogram per meter square (kg/m^2) Standard Deviation 1.049	0.01 Kilogram per meter square (kg/m^2) Standard Deviation 1.312	0.15 Kilogram per meter square (kg/m^2) Standard Deviation 0.682
Change From Baseline in Body Mass Index (BMI) Endpoint	0.65 Kilogram per meter square (kg/m^2) Standard Deviation 0.992	-0.07 Kilogram per meter square (kg/m^2) Standard Deviation 1.272	0.11 Kilogram per meter square (kg/m^2) Standard Deviation 0.705

SECONDARY outcome

Timeframe: Baseline, Day 35 (Cycle 3, 6, 9 and 12)

Population: 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.

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

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=29 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
Change From Baseline in Fasting Plasma Glucose Change at Cycle 6 Day 35	0.19 Millimoles per liter (mmol/L) Standard Error 0.19	-0.00 Millimoles per liter (mmol/L) Standard Error 0.19	0.27 Millimoles per liter (mmol/L) Standard Error 0.17
Change From Baseline in Fasting Plasma Glucose Change at Cycle 9 Day 35	0.10 Millimoles per liter (mmol/L) Standard Error 0.18	-0.10 Millimoles per liter (mmol/L) Standard Error 0.19	0.41 Millimoles per liter (mmol/L) Standard Error 0.16
Change From Baseline in Fasting Plasma Glucose Change at Cycle 3 Day 35	-0.07 Millimoles per liter (mmol/L) Standard Error 0.24	0.11 Millimoles per liter (mmol/L) Standard Error 0.23	0.61 Millimoles per liter (mmol/L) Standard Error 0.21
Change From Baseline in Fasting Plasma Glucose Change at Cycle 12 Day 35	0.29 Millimoles per liter (mmol/L) Standard Error 0.19	0.15 Millimoles per liter (mmol/L) Standard Error 0.19	0.26 Millimoles per liter (mmol/L) Standard Error 0.16

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=29 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
Change From Baseline in Glycated Hemoglobin (HbA1C) Change at Cycle 3 Day 35	0.14 Percentage of HbA1C Standard Error 0.06	-0.07 Percentage of HbA1C Standard Error 0.06	0.06 Percentage of HbA1C Standard Error 0.06
Change From Baseline in Glycated Hemoglobin (HbA1C) Change at Cycle 6 Day 35	0.09 Percentage of HbA1C Standard Error 0.06	-0.10 Percentage of HbA1C Standard Error 0.06	0.08 Percentage of HbA1C Standard Error 0.06
Change From Baseline in Glycated Hemoglobin (HbA1C) Change at Cycle 9 Day 35	0.16 Percentage of HbA1C Standard Error 0.06	-0.13 Percentage of HbA1C Standard Error 0.06	0.04 Percentage of HbA1C Standard Error 0.06
Change From Baseline in Glycated Hemoglobin (HbA1C) Change at Cycle 12 Day 35	0.18 Percentage of HbA1C Standard Error 0.06	-0.09 Percentage of HbA1C Standard Error 0.06	0.13 Percentage of HbA1C Standard Error 0.06

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=29 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides LDL Cholesterol: Change at Cycle 3 Day 35	0.08 mmol/L Standard Error 0.15	0.67 mmol/L Standard Error 0.15	0.91 mmol/L Standard Error 0.13
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides LDL Cholesterol: Change at Cycle 6 Day 35	-0.03 mmol/L Standard Error 0.15	0.36 mmol/L Standard Error 0.15	0.87 mmol/L Standard Error 0.13
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides LDL Cholesterol: Change at Cycle 9 Day 35	0.01 mmol/L Standard Error 0.14	0.28 mmol/L Standard Error 0.15	0.69 mmol/L Standard Error 0.13
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides LDL Cholesterol: Change at Cycle 12 Day 35	0.07 mmol/L Standard Error 0.15	0.31 mmol/L Standard Error 0.16	0.57 mmol/L Standard Error 0.13
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides HDL Cholesterol: Change at Cycle 12 Day 35	0.12 mmol/L Standard Error 0.05	0.21 mmol/L Standard Error 0.06	0.12 mmol/L Standard Error 0.05
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides Triglycerides: Change at Cycle 3 Day 35	0.27 mmol/L Standard Error 0.14	0.31 mmol/L Standard Error 0.14	0.34 mmol/L Standard Error 0.12
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides Cholesterol: Change at Cycle 3 Day 35	0.34 mmol/L Standard Error 0.16	0.98 mmol/L Standard Error 0.16	1.28 mmol/L Standard Error 0.13
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides Cholesterol: Change at Cycle 6 Day 35	0.18 mmol/L Standard Error 0.16	0.71 mmol/L Standard Error 0.16	1.35 mmol/L Standard Error 0.13
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides Cholesterol: Change at Cycle 9 Day 35	0.24 mmol/L Standard Error 0.16	0.66 mmol/L Standard Error 0.17	1.21 mmol/L Standard Error 0.14
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides Cholesterol: Change at Cycle 12 Day 35	0.38 mmol/L Standard Error 0.16	0.71 mmol/L Standard Error 0.17	0.92 mmol/L Standard Error 0.15
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides HDL Cholesterol: Change at Cycle 3 Day 35	0.08 mmol/L Standard Error 0.04	0.07 mmol/L Standard Error 0.05	0.13 mmol/L Standard Error 0.04
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides HDL Cholesterol: Change at Cycle 6 Day 35	0.09 mmol/L Standard Error 0.04	0.16 mmol/L Standard Error 0.05	0.12 mmol/L Standard Error 0.04
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides HDL Cholesterol: Change at Cycle 9 Day 35	0.10 mmol/L Standard Error 0.05	0.21 mmol/L Standard Error 0.05	0.17 mmol/L Standard Error 0.04
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides Triglycerides: Change at Cycle 6 Day 35	0.21 mmol/L Standard Error 0.15	0.14 mmol/L Standard Error 0.15	0.52 mmol/L Standard Error 0.13
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides Triglycerides: Change at Cycle 9 Day 35	0.30 mmol/L Standard Error 0.15	-0.01 mmol/L Standard Error 0.16	0.53 mmol/L Standard Error 0.14
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides Triglycerides: Change at Cycle 12 Day 35	0.43 mmol/L Standard Error 0.15	0.08 mmol/L Standard Error 0.16	0.28 mmol/L Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline, Cycle 12 Day 35

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

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=29 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
Change From Baseline in Bone Mineral Density (BMD) Femoral Neck	0.00 Gram per centimeter square (g/cm^2) Standard Error 0.03	0.07 Gram per centimeter square (g/cm^2) Standard Error 0.03	-0.02 Gram per centimeter square (g/cm^2) Standard Error 0.02
Change From Baseline in Bone Mineral Density (BMD) Lumbar Spine	0.00 Gram per centimeter square (g/cm^2) Standard Error 0.02	0.01 Gram per centimeter square (g/cm^2) Standard Error 0.02	-0.06 Gram per centimeter square (g/cm^2) Standard Error 0.02

SECONDARY outcome

Timeframe: Month 13 to Month 24

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. This outcome measure was planned to be analyzed and reported for LHRHa-based treatment arms.

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.

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=27 Participants 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.	Apalutamide n=30 Participants 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).	LHRHa + Apalutamide 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).
Median Time to Serum Testosterone Recovery to Greater Than (>) 50 ng/dL (Non-castrate) and > 150 ng/dL > 50 ng/dL	18.89 Months Interval 18.04 to 23.95	18.10 Months Interval 17.91 to 24.05	—
Median Time to Serum Testosterone Recovery to Greater Than (>) 50 ng/dL (Non-castrate) and > 150 ng/dL > 150 ng/dL	23.33 Months Interval 18.14 to 24.87	23.98 Months Interval 18.0 to 24.08	—

SECONDARY outcome

Timeframe: Baseline, Day 35 (Cycle 6 and Cycle 12)

Change from baseline in serum DHT levels was reported.

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=29 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
Change From Baseline in Serum Dihydrotestosterone (DHT) Levels Change at Cycle 6 Day 35	-0.90 Nanomoles per liter (nmol/L) Standard Error 0.26	0.93 Nanomoles per liter (nmol/L) Standard Error 0.27	-0.90 Nanomoles per liter (nmol/L) Standard Error 0.23
Change From Baseline in Serum Dihydrotestosterone (DHT) Levels Change at Cycle 12 Day 35	-0.90 Nanomoles per liter (nmol/L) Standard Error 0.24	0.86 Nanomoles per liter (nmol/L) Standard Error 0.25	-0.90 Nanomoles per liter (nmol/L) Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline, Day 35 (Cycle 6 and Cycle 12)

Change from baseline in estradiol levels was reported.

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=29 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
Change From Baseline in Estradiol Levels Change at Cycle 6 Day 35	-88.63 Picomoles per liter (pmol/L) Standard Error 12.24	87.87 Picomoles per liter (pmol/L) Standard Error 13.37	-94.11 Picomoles per liter (pmol/L) Standard Error 11.58
Change From Baseline in Estradiol Levels Change at Cycle 12 Day 35	-77.12 Picomoles per liter (pmol/L) Standard Error 13.46	81.29 Picomoles per liter (pmol/L) Standard Error 13.88	-103.01 Picomoles per liter (pmol/L) Standard Error 12.76

SECONDARY outcome

Timeframe: From date of 1st dose of study drug to date of last dose of study drug plus 30 days (up to 6 years)

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

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.

Outcome measures

Outcome measures
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=29 Participants 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.	Apalutamide n=29 Participants 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).	LHRHa + Apalutamide n=31 Participants 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).
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)	96.6 Percentage of participants	100.0 Percentage of participants	100.0 Percentage of participants

Adverse Events

Luteinizing Hormone Releasing Hormone Agonist (LHRHa)

Serious events: 3 serious events

Other events: 28 other events

Deaths: 1 deaths

Apalutamide

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

LHRHa + Apalutamide

Serious events: 5 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Luteinizing Hormone Releasing Hormone Agonist (LHRHa) n=29 participants at risk 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.	Apalutamide n=29 participants at risk 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).	LHRHa + Apalutamide n=31 participants at risk 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).
Cardiac disorders Acute Myocardial Infarction	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	3.2% 1/31 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.
Cardiac disorders Angina Pectoris	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	3.2% 1/31 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.
Cardiac disorders Atrial Fibrillation	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	3.2% 1/31 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.
Cardiac disorders Ventricular Tachycardia	3.4% 1/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/31 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.
Ear and labyrinth disorders Vertigo	3.4% 1/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/31 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.
Infections and infestations Wound Infection	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	3.2% 1/31 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.
Injury, poisoning and procedural complications Rib Fracture	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	3.2% 1/31 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.
Nervous system disorders Transient Ischaemic Attack	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	3.2% 1/31 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.
Product Issues Device Failure	3.4% 1/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/31 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	3.2% 1/31 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	3.2% 1/31 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.
Skin and subcutaneous tissue disorders Toxic Epidermal Necrolysis	3.4% 1/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/31 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.
Vascular disorders Hypertension	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	0.00% 0/29 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.	3.2% 1/31 • Up to 6 years The safety population included all participants who received at least 1 dose of study drug as actually treated.

Other adverse events

Additional Information

EXECUTIVE MEDICAL DIRECTOR

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER