The Role of Highly Selective Androgen Receptor (AR) Targe... | NCT01790126

ID	Type	Description	Link
ARN-509-002

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

Name	Type	Description	Arm Group Labels	Other Names
ARN-509	Drug		ARN-509 LHRH agonist + ARN-509
LHRH Agonist

Measure	Description	Time Frame
Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score 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.	Baseline, at 12 months

Measure	Description	Time Frame
Change From Baseline in FACT-P Total Score 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.

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Aragon Pharmaceuticals, Inc Clinical Trial	Aragon Pharmaceuticals, Inc.	Study Director

ID	Title	Description
FG000	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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 1, 2019	Feb 27, 2020

ID	Title	Description
BG000	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.
BG001	Apalutamide	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (830 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 (460 mg tablets).
BG002	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).
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00030 BG00129 BG00231 BG00390

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score 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.

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.

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline, at 12 months

ID	Title	Description
OG000	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.
OG001	Apalutamide	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (830 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 (460 mg tablets).
OG002	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).

Units	Counts
Participants	OG00030 OG00129 OG00231

Title

Denominators

Categories

Title	Measurements
	OG000-8.04± 2.40 OG001-6.60± 2.53 OG002-9.42± 2.30

Secondary

Change From Baseline in FACT-P Total Score at 3 and 24 Months

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

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline, at 3 and 24 months

ID	Title	Description
OG000	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.
OG001

Secondary

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

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.

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

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline, at 3, 12 and 24 months

ID	Title	Description
OG000	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.

Secondary

Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score 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).

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

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline, at 3, 12 and 24 months

ID	Title	Description
OG000	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.
OG001	Apalutamide

Secondary

Change From Baseline in Sexual Health Inventory for Men (SHIM) Total Score 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.

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

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline, at 3, 12, 24 months

ID	Title	Description
OG000	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.
OG001	Apalutamide	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (830 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 (460 mg tablets).

Secondary

Time to Prostate Specific Antigen (PSA) Progression Based on Modified Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria

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.

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

Posted

Median

95% Confidence Interval

Months

Up to 24 months

ID	Title	Description
OG000	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.
OG001	Apalutamide	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (830 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 (460 mg tablets).

Secondary

Percentage of Participants Without PSA or Radiographic Progression and With Recovery of Serum Testosterone

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]).

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.

Posted

Number

Percentage of participants

Up to 24 months

ID	Title	Description
OG000	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.

Secondary

Percentage of Participants With a Serum PSA Less Than 0.2 ng/mL

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

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.

Posted

Number

Percentage of participants

From 7 to 24 months

ID	Title	Description
OG000	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.
OG001	Apalutamide	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (830 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 (460 mg tablets).

Secondary

Change From Baseline in Body Mass Index (BMI)

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.

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.

Posted

Mean

Standard Deviation

Kilogram per meter square (kg/m^2)

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)

ID	Title	Description
OG000	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.
OG001	Apalutamide	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (830 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 (460 mg tablets).

Secondary

Change From Baseline in Fasting Plasma Glucose

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

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.

Posted

Least Squares Mean

Standard Error

Millimoles per liter (mmol/L)

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

ID	Title	Description
OG000	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.
OG001	Apalutamide	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (830 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 (460 mg tablets).

Secondary

Change From Baseline in Glycated Hemoglobin (HbA1C)

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

Posted

Least Squares Mean

Standard Error

Percentage of HbA1C

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

ID	Title	Description
OG000	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.
OG001	Apalutamide	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (830 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 (460 mg tablets).

Secondary

Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides

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

Posted

Least Squares Mean

Standard Error

mmol/L

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

ID	Title	Description
OG000	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.
OG001	Apalutamide	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (830 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 (460 mg tablets).

Secondary

Change From Baseline in Bone Mineral Density (BMD)

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

Posted

Least Squares Mean

Standard Error

Gram per centimeter square (g/cm^2)

Baseline, Cycle 12 Day 35

ID	Title	Description
OG000	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.
OG001	Apalutamide	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (830 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 (460 mg tablets).

Secondary

Median Time to Serum Testosterone Recovery to Greater Than (>) 50 ng/dL (Non-castrate) and > 150 ng/dL

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.

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.

Posted

Median

95% Confidence Interval

Months

Month 13 to Month 24

ID	Title	Description
OG000	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.
OG001	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).

Secondary

Change From Baseline in Serum Dihydrotestosterone (DHT) Levels

Change from baseline in serum DHT levels was reported.

Posted

Least Squares Mean

Standard Error

Nanomoles per liter (nmol/L)

Baseline, Day 35 (Cycle 6 and Cycle 12)

ID	Title	Description
OG000	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.
OG001	Apalutamide	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (830 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 (460 mg tablets).

Secondary

Change From Baseline in Estradiol Levels

Change from baseline in estradiol levels was reported.

Posted

Least Squares Mean

Standard Error

Picomoles per liter (pmol/L)

Baseline, Day 35 (Cycle 6 and Cycle 12)

ID	Title	Description
OG000	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.
OG001	Apalutamide	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (830 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 (460 mg tablets).

Secondary

Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)

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.

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

Posted

Number

Percentage of participants

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

ID	Title	Description
OG000	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.
OG001	Apalutamide

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0004 affected29 at risk EG0010 affected29 at risk EG0020 affected31 at risk
Angina Pectoris	Cardiac disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0010 affected29 at risk EG0022 affected31 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0013 affected29 at risk EG0020 affected31 at risk
Hypothyroidism	Endocrine disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0011 affected29 at risk EG0022 affected31 at risk
Eyelid Ptosis	Eye disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0012 affected29 at risk EG0020 affected31 at risk
Abdominal Discomfort	Gastrointestinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0015 affected29 at risk EG0022 affected31 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0013 affected29 at risk EG0024 affected31 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0012 affected29 at risk EG0023 affected31 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0017 affected29 at risk EG0024 affected31 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0013 affected29 at risk EG0022 affected31 at risk
Flatulence	Gastrointestinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0014 affected29 at risk EG0023 affected31 at risk
Gastrooesophageal Reflux Disease	Gastrointestinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0011 affected29 at risk EG0022 affected31 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0014 affected29 at risk EG0027 affected31 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0011 affected29 at risk EG0023 affected31 at risk
Asthenia	General disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0022 affected31 at risk
Fatigue	General disorders	MedDRA Version 21.1	Non-systematic Assessment	EG00022 affected29 at risk EG00119 affected29 at risk EG00224 affected31 at risk
Oedema Peripheral	General disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0011 affected29 at risk EG0023 affected31 at risk
Bronchitis	Infections and infestations	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0022 affected31 at risk
Conjunctivitis	Infections and infestations	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0012 affected29 at risk EG0020 affected31 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0013 affected29 at risk EG0024 affected31 at risk
Fall	Injury, poisoning and procedural complications	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0011 affected29 at risk EG0024 affected31 at risk
Aspartate Aminotransferase Increased	Investigations	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0010 affected29 at risk EG0020 affected31 at risk
Heart Rate Irregular	Investigations	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0012 affected29 at risk EG0020 affected31 at risk
Weight Decreased	Investigations	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0011 affected29 at risk EG0022 affected31 at risk
Weight Increased	Investigations	MedDRA Version 21.1	Non-systematic Assessment	EG0003 affected29 at risk EG0012 affected29 at risk EG0023 affected31 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0012 affected29 at risk EG0024 affected31 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0003 affected29 at risk EG0014 affected29 at risk EG0026 affected31 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0011 affected29 at risk EG0023 affected31 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0005 affected29 at risk EG0018 affected29 at risk EG0027 affected31 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0011 affected29 at risk EG0026 affected31 at risk
Muscle Atrophy	Musculoskeletal and connective tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0011 affected29 at risk EG0020 affected31 at risk
Muscle Spasms	Musculoskeletal and connective tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0011 affected29 at risk EG0021 affected31 at risk
Muscular Weakness	Musculoskeletal and connective tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0012 affected29 at risk EG0024 affected31 at risk
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0012 affected29 at risk EG0022 affected31 at risk
Osteopenia	Musculoskeletal and connective tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0010 affected29 at risk EG0020 affected31 at risk
Pain in Extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0011 affected29 at risk EG0026 affected31 at risk
Spinal Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0022 affected31 at risk
Basal Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0022 affected31 at risk
Cognitive Disorder	Nervous system disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0011 affected29 at risk EG0023 affected31 at risk
Dizziness	Nervous system disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0014 affected29 at risk EG0024 affected31 at risk
Dysgeusia	Nervous system disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0016 affected29 at risk EG0025 affected31 at risk
Headache	Nervous system disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0012 affected29 at risk EG0026 affected31 at risk
Memory Impairment	Nervous system disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0012 affected29 at risk EG0023 affected31 at risk
Paraesthesia	Nervous system disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0022 affected31 at risk
Anxiety	Psychiatric disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0012 affected29 at risk EG0021 affected31 at risk
Depression	Psychiatric disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0013 affected29 at risk EG0024 affected31 at risk
Insomnia	Psychiatric disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0011 affected29 at risk EG00210 affected31 at risk
Irritability	Psychiatric disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0010 affected29 at risk EG0020 affected31 at risk
Libido Decreased	Psychiatric disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0003 affected29 at risk EG0011 affected29 at risk EG0023 affected31 at risk
Loss of Libido	Psychiatric disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0010 affected29 at risk EG0020 affected31 at risk
Haematuria	Renal and urinary disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0003 affected29 at risk EG0011 affected29 at risk EG0021 affected31 at risk
Incontinence	Renal and urinary disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0022 affected31 at risk
Breast Tenderness	Reproductive system and breast disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0014 affected29 at risk EG0022 affected31 at risk
Erectile Dysfunction	Reproductive system and breast disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0013 affected29 at risk EG0021 affected31 at risk
Gynaecomastia	Reproductive system and breast disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0003 affected29 at risk EG00112 affected29 at risk EG0021 affected31 at risk
Nipple Pain	Reproductive system and breast disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG00112 affected29 at risk EG0020 affected31 at risk
Testicular Pain	Reproductive system and breast disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0011 affected29 at risk EG0021 affected31 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0012 affected29 at risk EG0022 affected31 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0012 affected29 at risk EG0020 affected31 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0002 affected29 at risk EG0012 affected29 at risk EG0023 affected31 at risk
Dyspnoea Exertional	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0012 affected29 at risk EG0021 affected31 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0011 affected29 at risk EG0022 affected31 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0014 affected29 at risk EG0023 affected31 at risk
Hypotrichosis	Skin and subcutaneous tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0022 affected31 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0012 affected29 at risk EG0022 affected31 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0015 affected29 at risk EG0025 affected31 at risk
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0013 affected29 at risk EG0020 affected31 at risk
Rash Pruritic	Skin and subcutaneous tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0012 affected29 at risk EG0021 affected31 at risk
Hot Flush	Vascular disorders	MedDRA Version 21.1	Non-systematic Assessment	EG00025 affected29 at risk EG0019 affected29 at risk EG00226 affected31 at risk
Hypertension	Vascular disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0011 affected29 at risk EG0026 affected31 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Scottsdale	Arizona		United States

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Term
C572045	apalutamide
D007987	Gonadotropin-Releasing Hormone
C493311	luprolide acetate gel depot
D016729	Leuprolide
D017273	Goserelin
D017329	Triptorelin Pamoate

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

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	1	29	3	29	28	29
EG001	Apalutamide	Participants received apalutamide, 240 milligram (mg) soft-gel capsules (830 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 (460 mg tablets).	0	29	0	29	29	29
EG002	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).	0	31	5	31	30	31

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute Myocardial Infarction	Cardiac disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0021 affected31 at risk
Angina Pectoris	Cardiac disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0021 affected31 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0021 affected31 at risk
Ventricular Tachycardia	Cardiac disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0010 affected29 at risk EG0020 affected31 at risk
Vertigo	Ear and labyrinth disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0010 affected29 at risk EG0020 affected31 at risk
Wound Infection	Infections and infestations	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0021 affected31 at risk
Rib Fracture	Injury, poisoning and procedural complications	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0021 affected31 at risk
Transient Ischaemic Attack	Nervous system disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0021 affected31 at risk
Device Failure	Product Issues	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0010 affected29 at risk EG0020 affected31 at risk
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0021 affected31 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0021 affected31 at risk
Toxic Epidermal Necrolysis	Skin and subcutaneous tissue disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0001 affected29 at risk EG0010 affected29 at risk EG0020 affected31 at risk
Hypertension	Vascular disorders	MedDRA Version 21.1	Non-systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0021 affected31 at risk