An Efficacy and Safety Study of Apalutamide (JNJ-56021927) in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Participants With Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC)

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ClinicalTrials.gov Identifier: NCT02257736

Recruitment Status : Active, not recruiting

First Posted : October 6, 2014

Results First Posted : August 16, 2021

Last Update Posted : April 25, 2024

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Sponsor:

Information provided by (Responsible Party):

Aragon Pharmaceuticals, Inc.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Prostatic Neoplasms
Interventions	Drug: Apalutamide Drug: Abiraterone acetate Drug: Prednisone Drug: Placebo
Enrollment	982

Participant Flow

Recruitment Details
Pre-assignment Details	Treatment disposition has been reported in participant flow.


Arm/Group Title	Placebo+ Abiraterone Acetate - Prednisolone	Apalutamide + Abiraterone Acetate - Prednisolone
Arm/Group Description	Participants received 4*60 milligra...	Participants received 4*60 mg table...
Arm/Group Description	Participants received 460 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.	Participants received 460 mg tablets of apalutamide tablets orally qd with or without food and 4250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
Period Title: Overall Study
Started	490	492
Completed	39	45
Not Completed	451	447
Reason Not Completed
Progressive disease	365	327
Adverse Event	45	56
Withdrawal by Subject	21	38
Death	11	6
Physician Decision	5	9
Non-Compliance with study drug	1	2
Protocol Violation	1	0
Other	1	7
Randomized, not treated	1	2

Baseline Characteristics

Arm/Group Title		Placebo+ Abiraterone Acetate - Prednisolone	Apalutamide + Abiraterone Acetate - Prednisolone	Total
Arm/Group Description		Participants received 4*60 milligra...	Participants received 4*60 mg table...	Total of all reporting groups
Arm/Group Description		Participants received 460 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.	Participants received 460 mg tablets of apalutamide tablets orally qd with or without food and 4250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.	Total of all reporting groups
Overall Number of Baseline Participants		490	492	982
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	490 participants	492 participants	982 participants
		70.7 (8.06)	71.4 (8.34)	71.1 (8.21)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	490 participants	492 participants	982 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	490 100.0%	492 100.0%	982 100.0%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	490 participants	492 participants	982 participants
	Hispanic or Latino	54 11.0%	50 10.2%	104 10.6%
	Not Hispanic or Latino	411 83.9%	422 85.8%	833 84.8%
	Unknown or Not Reported	25 5.1%	20 4.1%	45 4.6%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	490 participants	492 participants	982 participants
American Indian or Alaska Native		8 1.6%	9 1.8%	17 1.7%
Asian		53 10.8%	58 11.8%	111 11.3%
Black or African American		18 3.7%	19 3.9%	37 3.8%
Native Hawaiian or Other Pacific Islander		0 0.0%	0 0.0%	0 0.0%
White		373 76.1%	365 74.2%	738 75.2%
More than one race		0 0.0%	0 0.0%	0 0.0%
Unknown or Not Reported		20 4.1%	20 4.1%	40 4.1%
Other		18 3.7%	21 4.3%	39 4.0%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	490 participants	492 participants	982 participants
ARGENTINA		3 0.6%	3 0.6%	6 0.6%
AUSTRALIA		31 6.3%	47 9.6%	78 7.9%
BELGIUM		16 3.3%	16 3.3%	32 3.3%
BRAZIL		21 4.3%	18 3.7%	39 4.0%
CANADA		12 2.4%	18 3.7%	30 3.1%
FRANCE		18 3.7%	16 3.3%	34 3.5%
GERMANY		10 2.0%	9 1.8%	19 1.9%
ITALY		33 6.7%	36 7.3%	69 7.0%
JAPAN		23 4.7%	27 5.5%	50 5.1%
MEXICO		19 3.9%	16 3.3%	35 3.6%
NETHERLANDS		14 2.9%	16 3.3%	30 3.1%
RUSSIAN FEDERATION		59 12.0%	46 9.3%	105 10.7%
SOUTH AFRICA		9 1.8%	8 1.6%	17 1.7%
SOUTH KOREA		28 5.7%	29 5.9%	57 5.8%
SPAIN		43 8.8%	36 7.3%	79 8.0%
UNITED KINGDOM		23 4.7%	27 5.5%	50 5.1%
UNITED STATES		128 26.1%	124 25.2%	252 25.7%

Outcome Measures

1.Primary Outcome


Title	Radiographic Progression-free Survival (rPFS)
Description	The rPFS was defined as the time from randomization to the occurrence ...
Description	The rPFS was defined as the time from randomization to the occurrence of one of the following: 1) a participant was considered to have progressed by bone scan if - a) the first bone scan with greater than or equal to (>=) 2 new lesions compared to baseline was observed in less than (<) 12 weeks from randomization and was confirmed by a second bone scan taken >=6 weeks later showing >=2 additional new lesions (a total of >=4 new lesions compared to baseline), b) the first bone scan with >=2 new lesions compared to baseline was observed in >=12 weeks from randomization and the new lesions were verified on the next bone scan >=6 weeks later (a total of >=2 new lesions compared to baseline); 2) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Time Frame	Up to 3 years and 4 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.


Arm/Group Title	Placebo+ Abiraterone Acetate - Prednisolone	Apalutamide + Abiraterone Acetate - Prednisolone
Arm/Group Description:	Participants received 4*60 milligra...	Participants received 4*60 mg table...
Arm/Group Description:	Participants received 460 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.	Participants received 460 mg tablets of apalutamide tablets orally qd with or without food and 4250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
Overall Number of Participants Analyzed	490	492
Median (95% Confidence Interval) Unit of Measure: months
	16.59 (13.86 to 19.32)	23.98 (19.71 to 27.50)

2.Secondary Outcome


Title	Overall Survival (OS)
Description	The OS was defined as the time from randomization to date of death fro...
Description	The OS was defined as the time from randomization to date of death from any cause.
Time Frame	Up to 5 years and 10 months

Outcome Measure Data

Analysis Population Description

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


Arm/Group Title	Placebo+ Abiraterone Acetate - Prednisolone	Apalutamide + Abiraterone Acetate - Prednisolone
Arm/Group Description:	Participants received 4*60 milligra...	Participants received 4*60 mg table...
Arm/Group Description:	Participants received 460 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.	Participants received 460 mg tablets of apalutamide tablets orally qd with or without food and 4250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
Overall Number of Participants Analyzed	490	492
Median (95% Confidence Interval) Unit of Measure: months
	33.71 (31.24 to 38.28)	36.17 (32.76 to 38.77)

3.Secondary Outcome


Title	Time to Chronic Opioid Use
Description	Time to chronic opioid use was defined as the time from date of random...
Description	Time to chronic opioid use was defined as the time from date of randomization to the first date of opioid use.
Time Frame	Up to 5 years and 10 months

Outcome Measure Data

Analysis Population Description

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


Arm/Group Title	Placebo+ Abiraterone Acetate - Prednisolone	Apalutamide + Abiraterone Acetate - Prednisolone
Arm/Group Description:	Participants received 4*60 milligra...	Participants received 4*60 mg table...
Arm/Group Description:	Participants received 460 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.	Participants received 460 mg tablets of apalutamide tablets orally qd with or without food and 4250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
Overall Number of Participants Analyzed	490	492
Median (95% Confidence Interval) Unit of Measure: months
	53.26 ^[1] (42.02 to NA)	46.98 ^[1] (39.23 to NA)

[1]

Here 'NA' represents that upper limit of CI was not estimable due to lesser number of events.

4.Secondary Outcome


Title	Time to Initiation of Cytotoxic Chemotherapy
Description	Time to initiation of cytotoxic chemotherapy was defined as the time f...
Description	Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.
Time Frame	Up to 5 years and 10 months

Outcome Measure Data

Analysis Population Description

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


Arm/Group Title	Placebo+ Abiraterone Acetate - Prednisolone	Apalutamide + Abiraterone Acetate - Prednisolone
Arm/Group Description:	Participants received 4*60 milligra...	Participants received 4*60 mg table...
Arm/Group Description:	Participants received 460 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.	Participants received 460 mg tablets of apalutamide tablets orally qd with or without food and 4250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
Overall Number of Participants Analyzed	490	492
Median (95% Confidence Interval) Unit of Measure: months
	34.23 (29.54 to 39.16)	36.11 (32.23 to 42.55)

5.Secondary Outcome


Title	Time to Pain Progression
Description	Time to pain progression: time from randomization to first date that p...
Description	Time to pain progression: time from randomization to first date that participant either experienced an increase by 2 points from baseline in Brief Pain Inventory Short Form (BPI-SF) worst pain intensity item (item 3) or Case Report Form (CRF) pain, observed at 2 consecutive evaluations >=4 wks apart, or initiation of chronic opioids as defined in time to chronic opioid use, whichever occurred first. BPI-SF is a self-administered questionnaire developed to assess severity of pain and impact of pain on daily functions. Item 3(worst pain intensity) asks participants to rate worst pain in prior 7-days on a 0-10 numeric rating scale, where "0" indicates "No pain" and "10" indicates "Pain as bad as you can imagine." A lower score is better.CRF pain refers to participant's response to global pain assessment "How would you rate your pain over the past 7 days?"with a scale of 0("No pain") to 10("Pain as bad as you can imagine"),that is systematically reported and recorded on the eCRF.
Time Frame	Up to 5 years and 10 months

Outcome Measure Data

Analysis Population Description

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


Arm/Group Title	Placebo+ Abiraterone Acetate - Prednisolone	Apalutamide + Abiraterone Acetate - Prednisolone
Arm/Group Description:	Participants received 4*60 milligra...	Participants received 4*60 mg table...
Arm/Group Description:	Participants received 460 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.	Participants received 460 mg tablets of apalutamide tablets orally qd with or without food and 4250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
Overall Number of Participants Analyzed	490	492
Median (95% Confidence Interval) Unit of Measure: months
	26.51 (22.57 to 29.50)	21.82 (17.97 to 25.66)

Adverse Events

Time Frame	Up to 3 years and 4 months
Adverse Event Reporting Description	Safety Analysis set included all participants who received at least 1 dose of study drug, with treatment assignments designated according to actual study treatment received.

Arm/Group Title	Placebo+ Abiraterone Acetate - Prednisolone	Apalutamide + Abiraterone Acetate - Prednisolone
Arm/Group Description	Participants received 4*60 milligra...	Participants received 4*60 mg table...
Arm/Group Description	Participants received 460 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.	Participants received 460 mg tablets of apalutamide tablets orally qd with or without food and 4250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
All-Cause Mortality
	Placebo+ Abiraterone Acetate - Prednisolone	Apalutamide + Abiraterone Acetate - Prednisolone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	350/489 (71.57%)	338/490 (68.98%)
Serious Adverse Events Serious Adverse Events
	Placebo+ Abiraterone Acetate - Prednisolone	Apalutamide + Abiraterone Acetate - Prednisolone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	166/489 (33.95%)	192/490 (39.18%)
Blood and lymphatic system disorders
Anaemia ^* 1	5/489 (1.02%)	2/490 (0.41%)
Blood Loss Anaemia ^* 1	1/489 (0.20%)	0/490 (0.00%)
Disseminated Intravascular Coagulation ^* 1	1/489 (0.20%)	0/490 (0.00%)
Febrile Neutropenia ^* 1	4/489 (0.82%)	1/490 (0.20%)
Neutropenia ^* 1	0/489 (0.00%)	1/490 (0.20%)
Thrombocytopenia ^* 1	1/489 (0.20%)	0/490 (0.00%)
Cardiac disorders
Acute Left Ventricular Failure ^* 1	1/489 (0.20%)	0/490 (0.00%)
Acute Myocardial Infarction ^* 1	4/489 (0.82%)	4/490 (0.82%)
Angina Pectoris ^* 1	0/489 (0.00%)	4/490 (0.82%)
Aortic Valve Incompetence ^* 1	0/489 (0.00%)	1/490 (0.20%)
Aortic Valve Stenosis ^* 1	0/489 (0.00%)	1/490 (0.20%)
Atrial Fibrillation ^* 1	6/489 (1.23%)	3/490 (0.61%)
Atrioventricular Block Complete ^* 1	0/489 (0.00%)	1/490 (0.20%)
Bradycardia ^* 1	0/489 (0.00%)	2/490 (0.41%)
Cardiac Failure ^* 1	3/489 (0.61%)	2/490 (0.41%)
Cardiac Failure Chronic ^* 1	1/489 (0.20%)	0/490 (0.00%)
Cardiac Failure Congestive ^* 1	4/489 (0.82%)	4/490 (0.82%)
Coronary Artery Disease ^* 1	2/489 (0.41%)	1/490 (0.20%)
Coronary Artery Stenosis ^* 1	1/489 (0.20%)	0/490 (0.00%)
Left Ventricular Dysfunction ^* 1	0/489 (0.00%)	1/490 (0.20%)
Myocardial Infarction ^* 1	1/489 (0.20%)	6/490 (1.22%)
Palpitations ^* 1	0/489 (0.00%)	1/490 (0.20%)
Sinus Node Dysfunction ^* 1	1/489 (0.20%)	0/490 (0.00%)
Stress Cardiomyopathy ^* 1	0/489 (0.00%)	1/490 (0.20%)
Supraventricular Tachycardia ^* 1	0/489 (0.00%)	1/490 (0.20%)
Ventricular Tachycardia ^* 1	0/489 (0.00%)	2/490 (0.41%)
Endocrine disorders
Inappropriate Antidiuretic Hormone Secretion ^* 1	1/489 (0.20%)	0/490 (0.00%)
Eye disorders
Cataract ^* 1	1/489 (0.20%)	2/490 (0.41%)
Diplopia ^* 1	1/489 (0.20%)	0/490 (0.00%)
Visual Impairment ^* 1	0/489 (0.00%)	1/490 (0.20%)
Gastrointestinal disorders
Anal Haemorrhage ^* 1	1/489 (0.20%)	0/490 (0.00%)
Constipation ^* 1	2/489 (0.41%)	0/490 (0.00%)
Diarrhoea ^* 1	1/489 (0.20%)	2/490 (0.41%)
Diverticulum ^* 1	1/489 (0.20%)	0/490 (0.00%)
Diverticulum Intestinal Haemorrhagic ^* 1	2/489 (0.41%)	0/490 (0.00%)
Duodenal Ulcer Perforation ^* 1	1/489 (0.20%)	0/490 (0.00%)
Enteritis ^* 1	1/489 (0.20%)	0/490 (0.00%)
Food Poisoning ^* 1	1/489 (0.20%)	0/490 (0.00%)
Gastric Haemorrhage ^* 1	1/489 (0.20%)	0/490 (0.00%)
Gastritis ^* 1	0/489 (0.00%)	1/490 (0.20%)
Gastrointestinal Haemorrhage ^* 1	3/489 (0.61%)	2/490 (0.41%)
Haematochezia ^* 1	1/489 (0.20%)	0/490 (0.00%)
Inguinal Hernia ^* 1	0/489 (0.00%)	1/490 (0.20%)
Intestinal Obstruction ^* 1	2/489 (0.41%)	3/490 (0.61%)
Large Intestine Polyp ^* 1	1/489 (0.20%)	0/490 (0.00%)
Lumbar Hernia ^* 1	0/489 (0.00%)	1/490 (0.20%)
Melaena ^* 1	1/489 (0.20%)	0/490 (0.00%)
Nausea ^* 1	2/489 (0.41%)	0/490 (0.00%)
Pancreatitis ^* 1	0/489 (0.00%)	1/490 (0.20%)
Peptic Ulcer Perforation ^* 1	1/489 (0.20%)	0/490 (0.00%)
Periodontal Disease ^* 1	1/489 (0.20%)	0/490 (0.00%)
Proctitis ^* 1	0/489 (0.00%)	1/490 (0.20%)
Rectal Haemorrhage ^* 1	5/489 (1.02%)	0/490 (0.00%)
Small Intestinal Obstruction ^* 1	0/489 (0.00%)	1/490 (0.20%)
Vomiting ^* 1	1/489 (0.20%)	1/490 (0.20%)
General disorders
Asthenia ^* 1	2/489 (0.41%)	4/490 (0.82%)
Fatigue ^* 1	0/489 (0.00%)	1/490 (0.20%)
Gait Inability ^* 1	0/489 (0.00%)	1/490 (0.20%)
General Physical Health Deterioration ^* 1	3/489 (0.61%)	0/490 (0.00%)
Generalised Oedema ^* 1	1/489 (0.20%)	0/490 (0.00%)
Granuloma ^* 1	0/489 (0.00%)	1/490 (0.20%)
Multiple Organ Dysfunction Syndrome ^* 1	3/489 (0.61%)	0/490 (0.00%)
Non-Cardiac Chest Pain ^* 1	1/489 (0.20%)	5/490 (1.02%)
Oedema Peripheral ^* 1	2/489 (0.41%)	0/490 (0.00%)
Pyrexia ^* 1	4/489 (0.82%)	2/490 (0.41%)
Systemic Inflammatory Response Syndrome ^* 1	1/489 (0.20%)	0/490 (0.00%)
Hepatobiliary disorders
Bile Duct Stone ^* 1	0/489 (0.00%)	2/490 (0.41%)
Cholangitis ^* 1	2/489 (0.41%)	0/490 (0.00%)
Cholecystitis ^* 1	0/489 (0.00%)	1/490 (0.20%)
Cholelithiasis ^* 1	1/489 (0.20%)	0/490 (0.00%)
Cholestasis ^* 1	1/489 (0.20%)	0/490 (0.00%)
Hepatic Function Abnormal ^* 1	1/489 (0.20%)	0/490 (0.00%)
Immune system disorders
Anaphylactic Reaction ^* 1	0/489 (0.00%)	1/490 (0.20%)
Contrast Media Allergy ^* 1	0/489 (0.00%)	1/490 (0.20%)
Infections and infestations
Appendicitis ^* 1	1/489 (0.20%)	0/490 (0.00%)
Appendicitis Perforated ^* 1	1/489 (0.20%)	0/490 (0.00%)
Bacteraemia ^* 1	1/489 (0.20%)	1/490 (0.20%)
Bronchitis ^* 1	1/489 (0.20%)	2/490 (0.41%)
Catheter Site Infection ^* 1	1/489 (0.20%)	0/490 (0.00%)
Cellulitis ^* 1	1/489 (0.20%)	1/490 (0.20%)
Clostridium Difficile Colitis ^* 1	1/489 (0.20%)	0/490 (0.00%)
Diverticulitis ^* 1	2/489 (0.41%)	1/490 (0.20%)
Erysipelas ^* 1	0/489 (0.00%)	1/490 (0.20%)
Gangrene ^* 1	1/489 (0.20%)	0/490 (0.00%)
Gastroenteritis ^* 1	2/489 (0.41%)	2/490 (0.41%)
Gastroenteritis Viral ^* 1	0/489 (0.00%)	1/490 (0.20%)
Gastrointestinal Infection ^* 1	1/489 (0.20%)	0/490 (0.00%)
Herpes Zoster ^* 1	0/489 (0.00%)	1/490 (0.20%)
Infection ^* 1	1/489 (0.20%)	0/490 (0.00%)
Influenza ^* 1	2/489 (0.41%)	0/490 (0.00%)
Legionella Infection ^* 1	0/489 (0.00%)	1/490 (0.20%)
Liver Abscess ^* 1	1/489 (0.20%)	0/490 (0.00%)
Localised Infection ^* 1	0/489 (0.00%)	1/490 (0.20%)
Lower Respiratory Tract Infection ^* 1	1/489 (0.20%)	2/490 (0.41%)
Osteomyelitis ^* 1	1/489 (0.20%)	2/490 (0.41%)
Pharyngitis ^* 1	0/489 (0.00%)	1/490 (0.20%)
Pneumonia ^* 1	10/489 (2.04%)	18/490 (3.67%)
Pneumonia Klebsiella ^* 1	0/489 (0.00%)	1/490 (0.20%)
Pneumonia Legionella ^* 1	0/489 (0.00%)	1/490 (0.20%)
Post Procedural Infection ^* 1	1/489 (0.20%)	0/490 (0.00%)
Prostate Infection ^* 1	0/489 (0.00%)	1/490 (0.20%)
Pseudomembranous Colitis ^* 1	1/489 (0.20%)	0/490 (0.00%)
Pulmonary Mycosis ^* 1	1/489 (0.20%)	0/490 (0.00%)
Pulmonary Tuberculosis ^* 1	1/489 (0.20%)	0/490 (0.00%)
Pyelonephritis ^* 1	1/489 (0.20%)	4/490 (0.82%)
Renal Abscess ^* 1	1/489 (0.20%)	0/490 (0.00%)
Respiratory Tract Infection ^* 1	1/489 (0.20%)	1/490 (0.20%)
Sepsis ^* 1	7/489 (1.43%)	5/490 (1.02%)
Septic Shock ^* 1	2/489 (0.41%)	1/490 (0.20%)
Sinusitis ^* 1	0/489 (0.00%)	1/490 (0.20%)
Staphylococcal Infection ^* 1	0/489 (0.00%)	1/490 (0.20%)
Tracheobronchitis ^* 1	0/489 (0.00%)	1/490 (0.20%)
Upper Respiratory Tract Infection ^* 1	2/489 (0.41%)	0/490 (0.00%)
Urinary Tract Infection ^* 1	7/489 (1.43%)	12/490 (2.45%)
Urosepsis ^* 1	2/489 (0.41%)	2/490 (0.41%)
Injury, poisoning and procedural complications
Alcohol Poisoning ^* 1	0/489 (0.00%)	1/490 (0.20%)
Ankle Fracture ^* 1	0/489 (0.00%)	1/490 (0.20%)
Cervical Vertebral Fracture ^* 1	1/489 (0.20%)	0/490 (0.00%)
Clavicle Fracture ^* 1	0/489 (0.00%)	1/490 (0.20%)
Fall ^* 1	1/489 (0.20%)	8/490 (1.63%)
Femoral Neck Fracture ^* 1	0/489 (0.00%)	1/490 (0.20%)
Femur Fracture ^* 1	1/489 (0.20%)	3/490 (0.61%)
Foot Fracture ^* 1	0/489 (0.00%)	1/490 (0.20%)
Hand Fracture ^* 1	0/489 (0.00%)	2/490 (0.41%)
Hip Fracture ^* 1	0/489 (0.00%)	1/490 (0.20%)
Humerus Fracture ^* 1	0/489 (0.00%)	1/490 (0.20%)
Limb Traumatic Amputation ^* 1	0/489 (0.00%)	1/490 (0.20%)
Lower Limb Fracture ^* 1	1/489 (0.20%)	0/490 (0.00%)
Lumbar Vertebral Fracture ^* 1	2/489 (0.41%)	0/490 (0.00%)
Multiple Fractures ^* 1	0/489 (0.00%)	1/490 (0.20%)
Muscle Strain ^* 1	1/489 (0.20%)	0/490 (0.00%)
Pelvic Fracture ^* 1	0/489 (0.00%)	1/490 (0.20%)
Radius Fracture ^* 1	1/489 (0.20%)	0/490 (0.00%)
Rib Fracture ^* 1	0/489 (0.00%)	1/490 (0.20%)
Spinal Compression Fracture ^* 1	0/489 (0.00%)	2/490 (0.41%)
Spinal Fracture ^* 1	0/489 (0.00%)	1/490 (0.20%)
Subdural Haematoma ^* 1	0/489 (0.00%)	2/490 (0.41%)
Toxicity to Various Agents ^* 1	0/489 (0.00%)	1/490 (0.20%)
Traumatic Fracture ^* 1	0/489 (0.00%)	1/490 (0.20%)
Upper Limb Fracture ^* 1	1/489 (0.20%)	0/490 (0.00%)
Investigations
Alanine Aminotransferase Increased ^* 1	1/489 (0.20%)	0/490 (0.00%)
Blood Creatinine Increased ^* 1	0/489 (0.00%)	2/490 (0.41%)
Oxygen Saturation Decreased ^* 1	0/489 (0.00%)	1/490 (0.20%)
Metabolism and nutrition disorders
Decreased Appetite ^* 1	2/489 (0.41%)	0/490 (0.00%)
Dehydration ^* 1	2/489 (0.41%)	2/490 (0.41%)
Diabetes Mellitus ^* 1	0/489 (0.00%)	1/490 (0.20%)
Diabetes Mellitus Inadequate Control ^* 1	1/489 (0.20%)	0/490 (0.00%)
Failure to Thrive ^* 1	0/489 (0.00%)	1/490 (0.20%)
Hyperglycaemia ^* 1	3/489 (0.61%)	1/490 (0.20%)
Hyperkalaemia ^* 1	1/489 (0.20%)	0/490 (0.00%)
Hypokalaemia ^* 1	2/489 (0.41%)	2/490 (0.41%)
Hyponatraemia ^* 1	1/489 (0.20%)	0/490 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	0/489 (0.00%)	4/490 (0.82%)
Back Pain ^* 1	8/489 (1.64%)	4/490 (0.82%)
Bone Pain ^* 1	2/489 (0.41%)	3/490 (0.61%)
Flank Pain ^* 1	0/489 (0.00%)	1/490 (0.20%)
Muscular Weakness ^* 1	3/489 (0.61%)	0/490 (0.00%)
Osteoarthritis ^* 1	0/489 (0.00%)	2/490 (0.41%)
Osteoporosis ^* 1	0/489 (0.00%)	1/490 (0.20%)
Pain in Extremity ^* 1	0/489 (0.00%)	3/490 (0.61%)
Pathological Fracture ^* 1	3/489 (0.61%)	2/490 (0.41%)
Rheumatoid Arthritis ^* 1	0/489 (0.00%)	1/490 (0.20%)
Spinal Osteoarthritis ^* 1	0/489 (0.00%)	1/490 (0.20%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Astrocytoma ^* 1	1/489 (0.20%)	0/490 (0.00%)
B-Cell Lymphoma ^* 1	1/489 (0.20%)	0/490 (0.00%)
Basal Cell Carcinoma ^* 1	1/489 (0.20%)	1/490 (0.20%)
Bladder Transitional Cell Carcinoma ^* 1	1/489 (0.20%)	0/490 (0.00%)
Cancer Pain ^* 1	1/489 (0.20%)	0/490 (0.00%)
Colon Cancer ^* 1	1/489 (0.20%)	0/490 (0.00%)
Colorectal Adenocarcinoma ^* 1	0/489 (0.00%)	1/490 (0.20%)
Gallbladder Cancer ^* 1	0/489 (0.00%)	1/490 (0.20%)
Gastric Neoplasm ^* 1	1/489 (0.20%)	0/490 (0.00%)
Hepatic Cancer ^* 1	0/489 (0.00%)	1/490 (0.20%)
Intestinal Metastasis ^* 1	0/489 (0.00%)	1/490 (0.20%)
Intraductal Papillary Mucinous Neoplasm ^* 1	0/489 (0.00%)	1/490 (0.20%)
Lung Adenocarcinoma ^* 1	1/489 (0.20%)	0/490 (0.00%)
Malignant Melanoma ^* 1	0/489 (0.00%)	1/490 (0.20%)
Metastases to Bone ^* 1	0/489 (0.00%)	1/490 (0.20%)
Metastatic Malignant Melanoma ^* 1	0/489 (0.00%)	1/490 (0.20%)
Oesophageal Adenocarcinoma ^* 1	0/489 (0.00%)	1/490 (0.20%)
Oesophageal Neoplasm ^* 1	0/489 (0.00%)	1/490 (0.20%)
Pancreatic Carcinoma ^* 1	0/489 (0.00%)	1/490 (0.20%)
Prostate Cancer Metastatic ^* 1	1/489 (0.20%)	0/490 (0.00%)
Small Cell Carcinoma ^* 1	0/489 (0.00%)	1/490 (0.20%)
Squamous Cell Carcinoma ^* 1	0/489 (0.00%)	1/490 (0.20%)
Thyroid Cancer ^* 1	0/489 (0.00%)	1/490 (0.20%)
Transitional Cell Carcinoma ^* 1	0/489 (0.00%)	1/490 (0.20%)
Nervous system disorders
Altered State of Consciousness ^* 1	0/489 (0.00%)	1/490 (0.20%)
Carotid Artery Stenosis ^* 1	2/489 (0.41%)	0/490 (0.00%)
Cerebral Haemorrhage ^* 1	0/489 (0.00%)	1/490 (0.20%)
Cerebrovascular Accident ^* 1	4/489 (0.82%)	2/490 (0.41%)
Cognitive Disorder ^* 1	0/489 (0.00%)	1/490 (0.20%)
Dementia ^* 1	1/489 (0.20%)	1/490 (0.20%)
Dizziness ^* 1	1/489 (0.20%)	1/490 (0.20%)
Embolic Cerebral Infarction ^* 1	1/489 (0.20%)	0/490 (0.00%)
Encephalopathy ^* 1	1/489 (0.20%)	0/490 (0.00%)
Haemorrhagic Stroke ^* 1	0/489 (0.00%)	1/490 (0.20%)
Headache ^* 1	0/489 (0.00%)	1/490 (0.20%)
Ischaemic Stroke ^* 1	2/489 (0.41%)	1/490 (0.20%)
Loss of Consciousness ^* 1	1/489 (0.20%)	0/490 (0.00%)
Nervous System Disorder ^* 1	1/489 (0.20%)	0/490 (0.00%)
Neuralgia ^* 1	0/489 (0.00%)	1/490 (0.20%)
Parkinson's Disease ^* 1	1/489 (0.20%)	0/490 (0.00%)
Peripheral Motor Neuropathy ^* 1	1/489 (0.20%)	0/490 (0.00%)
Presyncope ^* 1	3/489 (0.61%)	1/490 (0.20%)
Sciatica ^* 1	0/489 (0.00%)	1/490 (0.20%)
Seizure ^* 1	0/489 (0.00%)	2/490 (0.41%)
Spinal Cord Compression ^* 1	3/489 (0.61%)	5/490 (1.02%)
Subarachnoid Haemorrhage ^* 1	1/489 (0.20%)	0/490 (0.00%)
Syncope ^* 1	5/489 (1.02%)	6/490 (1.22%)
Transient Ischaemic Attack ^* 1	1/489 (0.20%)	3/490 (0.61%)
Product Issues
Device Occlusion ^* 1	0/489 (0.00%)	2/490 (0.41%)
Psychiatric disorders
Anxiety ^* 1	1/489 (0.20%)	1/490 (0.20%)
Confusional State ^* 1	0/489 (0.00%)	1/490 (0.20%)
Delirium ^* 1	0/489 (0.00%)	1/490 (0.20%)
Renal and urinary disorders
Acute Kidney Injury ^* 1	7/489 (1.43%)	6/490 (1.22%)
Bladder Obstruction ^* 1	0/489 (0.00%)	1/490 (0.20%)
Calculus Bladder ^* 1	1/489 (0.20%)	1/490 (0.20%)
Haematuria ^* 1	13/489 (2.66%)	6/490 (1.22%)
Hydronephrosis ^* 1	0/489 (0.00%)	4/490 (0.82%)
Nephrolithiasis ^* 1	2/489 (0.41%)	1/490 (0.20%)
Oliguria ^* 1	1/489 (0.20%)	0/490 (0.00%)
Renal Failure ^* 1	0/489 (0.00%)	1/490 (0.20%)
Renal Impairment ^* 1	0/489 (0.00%)	1/490 (0.20%)
Ureteric Obstruction ^* 1	0/489 (0.00%)	1/490 (0.20%)
Urethral Stenosis ^* 1	1/489 (0.20%)	1/490 (0.20%)
Urinary Incontinence ^* 1	1/489 (0.20%)	3/490 (0.61%)
Urinary Retention ^* 1	3/489 (0.61%)	3/490 (0.61%)
Urinary Tract Obstruction ^* 1	1/489 (0.20%)	4/490 (0.82%)
Reproductive system and breast disorders
Testicular Pain ^* 1	0/489 (0.00%)	1/490 (0.20%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure ^* 1	1/489 (0.20%)	1/490 (0.20%)
Chronic Obstructive Pulmonary Disease ^* 1	2/489 (0.41%)	1/490 (0.20%)
Cough ^* 1	1/489 (0.20%)	0/490 (0.00%)
Dyspnoea ^* 1	1/489 (0.20%)	0/490 (0.00%)
Epistaxis ^* 1	1/489 (0.20%)	1/490 (0.20%)
Pneumothorax ^* 1	1/489 (0.20%)	1/490 (0.20%)
Pulmonary Congestion ^* 1	1/489 (0.20%)	0/490 (0.00%)
Pulmonary Embolism ^* 1	6/489 (1.23%)	1/490 (0.20%)
Pulmonary Fibrosis ^* 1	1/489 (0.20%)	0/490 (0.00%)
Pulmonary Oedema ^* 1	1/489 (0.20%)	0/490 (0.00%)
Respiratory Failure ^* 1	3/489 (0.61%)	0/490 (0.00%)
Skin and subcutaneous tissue disorders
Rash ^* 1	0/489 (0.00%)	2/490 (0.41%)
Rash Pruritic ^* 1	0/489 (0.00%)	1/490 (0.20%)
Skin Ulcer ^* 1	1/489 (0.20%)	0/490 (0.00%)
Subcutaneous Emphysema ^* 1	1/489 (0.20%)	0/490 (0.00%)
Surgical and medical procedures
Coronary Angioplasty ^* 1	1/489 (0.20%)	0/490 (0.00%)
Vascular disorders
Aortic Aneurysm ^* 1	2/489 (0.41%)	2/490 (0.41%)
Aortic Dissection ^* 1	0/489 (0.00%)	1/490 (0.20%)
Aortic Stenosis ^* 1	1/489 (0.20%)	0/490 (0.00%)
Deep Vein Thrombosis ^* 1	4/489 (0.82%)	1/490 (0.20%)
Embolism ^* 1	2/489 (0.41%)	0/490 (0.00%)
Haemodynamic Instability ^* 1	1/489 (0.20%)	0/490 (0.00%)
Hypertension ^* 1	3/489 (0.61%)	1/490 (0.20%)
Hypertensive Urgency ^* 1	0/489 (0.00%)	1/490 (0.20%)
Hypotension ^* 1	1/489 (0.20%)	1/490 (0.20%)
Pelvic Venous Thrombosis ^* 1	1/489 (0.20%)	0/490 (0.00%)
Peripheral Arterial Occlusive Disease ^* 1	1/489 (0.20%)	0/490 (0.00%)
Peripheral Ischaemia ^* 1	0/489 (0.00%)	1/490 (0.20%)
Thrombosis ^* 1	0/489 (0.00%)	1/490 (0.20%)
1 Term from vocabulary, MedDRA Version 23.0 * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo+ Abiraterone Acetate - Prednisolone	Apalutamide + Abiraterone Acetate - Prednisolone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	459/489 (93.87%)	472/490 (96.33%)
Blood and lymphatic system disorders
Anaemia ^* 1	77/489 (15.75%)	70/490 (14.29%)
Endocrine disorders
Hypothyroidism ^* 1	8/489 (1.64%)	27/490 (5.51%)
Gastrointestinal disorders
Abdominal Pain ^* 1	25/489 (5.11%)	24/490 (4.90%)
Constipation ^* 1	94/489 (19.22%)	96/490 (19.59%)
Diarrhoea ^* 1	73/489 (14.93%)	91/490 (18.57%)
Dyspepsia ^* 1	21/489 (4.29%)	28/490 (5.71%)
Nausea ^* 1	76/489 (15.54%)	84/490 (17.14%)
Vomiting ^* 1	35/489 (7.16%)	39/490 (7.96%)
General disorders
Asthenia ^* 1	63/489 (12.88%)	65/490 (13.27%)
Fatigue ^* 1	134/489 (27.40%)	164/490 (33.47%)
Oedema Peripheral ^* 1	72/489 (14.72%)	77/490 (15.71%)
Pyrexia ^* 1	36/489 (7.36%)	36/490 (7.35%)
Infections and infestations
Influenza ^* 1	28/489 (5.73%)	20/490 (4.08%)
Nasopharyngitis ^* 1	57/489 (11.66%)	52/490 (10.61%)
Upper Respiratory Tract Infection ^* 1	40/489 (8.18%)	42/490 (8.57%)
Urinary Tract Infection ^* 1	49/489 (10.02%)	37/490 (7.55%)
Injury, poisoning and procedural complications
Contusion ^* 1	49/489 (10.02%)	34/490 (6.94%)
Fall ^* 1	92/489 (18.81%)	106/490 (21.63%)
Rib Fracture ^* 1	23/489 (4.70%)	25/490 (5.10%)
Investigations
Alanine Aminotransferase Increased ^* 1	57/489 (11.66%)	20/490 (4.08%)
Aspartate Aminotransferase Increased ^* 1	53/489 (10.84%)	21/490 (4.29%)
Blood Alkaline Phosphatase Increased ^* 1	34/489 (6.95%)	19/490 (3.88%)
Blood Pressure Increased ^* 1	17/489 (3.48%)	26/490 (5.31%)
Weight Decreased ^* 1	84/489 (17.18%)	136/490 (27.76%)
Weight Increased ^* 1	28/489 (5.73%)	12/490 (2.45%)
Metabolism and nutrition disorders
Decreased Appetite ^* 1	60/489 (12.27%)	72/490 (14.69%)
Hypercholesterolaemia ^* 1	18/489 (3.68%)	28/490 (5.71%)
Hyperglycaemia ^* 1	37/489 (7.57%)	29/490 (5.92%)
Hypokalaemia ^* 1	73/489 (14.93%)	79/490 (16.12%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	121/489 (24.74%)	127/490 (25.92%)
Back Pain ^* 1	133/489 (27.20%)	154/490 (31.43%)
Bone Pain ^* 1	48/489 (9.82%)	34/490 (6.94%)
Muscle Spasms ^* 1	45/489 (9.20%)	30/490 (6.12%)
Musculoskeletal Chest Pain ^* 1	50/489 (10.22%)	48/490 (9.80%)
Musculoskeletal Pain ^* 1	46/489 (9.41%)	50/490 (10.20%)
Myalgia ^* 1	28/489 (5.73%)	27/490 (5.51%)
Neck Pain ^* 1	13/489 (2.66%)	26/490 (5.31%)
Pain in Extremity ^* 1	57/489 (11.66%)	79/490 (16.12%)
Nervous system disorders
Dizziness ^* 1	46/489 (9.41%)	61/490 (12.45%)
Dysgeusia ^* 1	12/489 (2.45%)	33/490 (6.73%)
Headache ^* 1	63/489 (12.88%)	79/490 (16.12%)
Psychiatric disorders
Anxiety ^* 1	16/489 (3.27%)	28/490 (5.71%)
Insomnia ^* 1	30/489 (6.13%)	46/490 (9.39%)
Renal and urinary disorders
Haematuria ^* 1	40/489 (8.18%)	42/490 (8.57%)
Pollakiuria ^* 1	31/489 (6.34%)	21/490 (4.29%)
Respiratory, thoracic and mediastinal disorders
Cough ^* 1	66/489 (13.50%)	53/490 (10.82%)
Dyspnoea ^* 1	43/489 (8.79%)	41/490 (8.37%)
Skin and subcutaneous tissue disorders
Rash ^* 1	24/489 (4.91%)	44/490 (8.98%)
Vascular disorders
Hot Flush ^* 1	56/489 (11.45%)	74/490 (15.10%)
Hypertension ^* 1	122/489 (24.95%)	144/490 (29.39%)
1 Term from vocabulary, MedDRA Version 23.0 * Indicates events were collected by non-systematic assessment

Limitations and Caveats

This study used an electronic handheld device to collect responses for patient-reported outcome (PRO) questionnaires, which might have resulted in a lower-than-expected compliance due to unfamiliarity of the elderly population with the device.

More Information

Certain Agreements

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

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

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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Executive Medical Director
Organization:	Aragon Pharmaceuticals, Inc.
Phone:	844-434-4210
EMail:	ClinicalTrialDisclosure@its.jnj.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Saad F, Efstathiou E, Attard G, Flaig TW, Franke F, Goodman OB Jr, Oudard S, Steuber T, Suzuki H, Wu D, Yeruva K, De Porre P, Brookman-May S, Li S, Li J, Thomas S, Bevans KB, Mundle SD, McCarthy SA, Rathkopf DE; ACIS Investigators. Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castration-resistant prostate cancer (ACIS): a randomised, placebo-controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2021 Nov;22(11):1541-1559. doi: 10.1016/S1470-2045(21)00402-2. Epub 2021 Sep 30.

Layout table for additonal information

Responsible Party:	Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT02257736
Other Study ID Numbers:	CR105505 56021927PCR3001 ( Other Identifier: Janssen Research & Development, LLC ) 2014-001718-25 ( EudraCT Number )
First Submitted:	October 2, 2014
First Posted:	October 6, 2014
Results First Submitted:	July 21, 2021
Results First Posted:	August 16, 2021
Last Update Posted:	April 25, 2024

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