Abiraterone Acetate in Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy

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ClinicalTrials.gov Identifier: NCT00638690

Recruitment Status : Completed

First Posted : March 19, 2008

Results First Posted : May 16, 2013

Last Update Posted : April 30, 2014

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Sponsor:

Information provided by (Responsible Party):

Cougar Biotechnology, Inc.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Prostatic Neoplasms
Interventions	Drug: Placebo Drug: Abiraterone acetate Drug: Prednisone/prednisolone
Enrollment	1195

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Abiraterone Acetate	Placebo
Arm/Group Description	Abiraterone acetate plus prednisone...	Placebo plus prednisone/prednisolon...
Arm/Group Description	Abiraterone acetate plus prednisone/prednisolone administered as four 250 mg tablets of abiraterone acetate once daily plus 5 mg prednisone/5 mg prednisolone twice daily until disease progression.	Placebo plus prednisone/prednisolone administered as four placebo tablets once daily plus 5 mg prednisone/5 mg prednisolone tablet twice daily until disease progression.
Period Title: Overall Study
Started	797	398
Completed	116	56
Not Completed	681	342
Reason Not Completed
Death	655	335
Withdrawal by Subject	22	5
Lost to Follow-up	4	2

Baseline Characteristics

Arm/Group Title		Abiraterone Acetate	Placebo	Total
Arm/Group Description		Abiraterone acetate plus prednisone...	Placebo plus prednisone/prednisolon...	Total of all reporting groups
Arm/Group Description		Abiraterone acetate plus prednisone/prednisolone administered as four 250 mg tablets of abiraterone acetate once daily plus 5 mg prednisone/5 mg prednisolone twice daily until disease progression.	Placebo plus prednisone/prednisolone	Total of all reporting groups
Overall Number of Baseline Participants		797	398	1195
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	797 participants	398 participants	1195 participants
		69.1 (8.4)	68.9 (8.61)	69 (8.46)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	797 participants	398 participants	1195 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	797 100.0%	398 100.0%	1195 100.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	797 participants	398 participants	1195 participants
Australia		69	35	104
Austria		11	1	12
Belgium		32	11	43
Canada		97	57	154
France		57	33	90
Germany		26	12	38
Hungary		5	2	7
Italy		21	12	33
Netherlands		4	2	6
Republic of Ireland		7	7	14
Spain		13	3	16
United Kingdom		119	61	180
United States		336	162	498

Outcome Measures

1.Primary Outcome


Title	Overall Survival
Description	Overall survival is defined as the time interval from the date of rand...
Description	Overall survival is defined as the time interval from the date of randomization to the date of death from any cause.
Time Frame	Up to 60 months

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Intent-to-Treat (ITT) population. The ITT population is composed of all patients randomized into the study and who will be classified according to their assigned teatment group, regardless of the actual treatment received.


Arm/Group Title	Abiraterone Acetate	Placebo
Arm/Group Description:	Abiraterone acetate plus prednisone...	Placebo plus prednisone/prednisolon...
Arm/Group Description:	Abiraterone acetate plus prednisone/prednisolone administered as four 250 mg tablets of abiraterone acetate once daily plus 5 mg prednisone/5 mg prednisolone twice daily until disease progression.	Placebo plus prednisone/prednisolone administered as four placebo tablets once daily plus 5 mg prednisone/5 mg prednisolone tablet twice daily until disease progression.
Overall Number of Participants Analyzed	797	398
Median (95% Confidence Interval) Unit of Measure: Days
	450.0 (430.0 to 470.0)	332.0 (310.0 to 366.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abiraterone Acetate, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Nominal P-value is 0.0142 at interim analysis based on group sequential design.
	Method	Log Rank
	Comments	This was a stratified analysis.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.646
	Confidence Interval	(2-Sided) 95% 0.543 to 0.768
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Time to Prostate-Specific Antigen Progression According to Prostate Specific Antigen Working Group Criteria
Description	The time interval from the date of randomization to the date of the pr...
Description	The time interval from the date of randomization to the date of the prostate-specific antigen (PSA) progression as defined in the protocol-specific Prostate Specific Antigen Working Group (PSAWG) criteria, namely, a PSA level of at least 5 ng/ml that has risen on at least 2 successive occasions, at least 2 weeks apart.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Abiraterone Acetate	Placebo
Arm/Group Description:	Abiraterone acetate plus prednisone...	Placebo plus prednisone/prednisolon...
Arm/Group Description:	Abiraterone acetate plus prednisone/prednisolone administered as four 250 mg tablets of abiraterone acetate once daily plus 5 mg prednisone/5 mg prednisolone twice daily until disease progression.	Placebo plus prednisone/prednisolone administered as four placebo tablets once daily plus 5 mg prednisone/5 mg prednisolone tablet twice daily until disease progression.
Overall Number of Participants Analyzed	797	398
Median (95% Confidence Interval) Unit of Measure: Days
	309.0 (255.0 to 421.0)	200.0 (170.0 to 254.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abiraterone Acetate, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Nominal P-value = 0.05.
	Method	Log Rank
	Comments	This was a stratified analysis.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.580
	Confidence Interval	95% 0.462 to 0.728
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Number of Patients Achieving a Prostate-Specific Antigen Decline >=50%
Description	A prostate-specific antigen (PSA) response was defined as a >=50% d...
Description	A prostate-specific antigen (PSA) response was defined as a >=50% decline from baseline.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Abiraterone Acetate	Placebo
Arm/Group Description:	Abiraterone acetate plus prednisone...	Placebo plus prednisone/prednisolon...
Arm/Group Description:	Abiraterone acetate plus prednisone/prednisolone administered as four 250 mg tablets of abiraterone acetate once daily plus 5 mg prednisone/5 mg prednisolone twice daily until disease progression.	Placebo plus prednisone/prednisolone administered as four placebo tablets once daily plus 5 mg prednisone/5 mg prednisolone tablet twice daily until disease progression.
Overall Number of Participants Analyzed	797	398
Measure Type: Number Unit of Measure: Participants
	232	22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abiraterone Acetate, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Nominal P-value = 0.05.
	Method	Chi-squared
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	5.266
	Confidence Interval	(2-Sided) 95% 3.459 to 8.018
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Radiographic Progression-free Survival
Description	Radiographic progression-free survival is based on imaging studies acc...
Description	Radiographic progression-free survival is based on imaging studies according to modified Response Evaluation Criteria in Solid Tumors (RECIST): baseline lymph node size must be >=2.0 cm to be considered a target lesion; progression on bone scans with >=2 new lesions not consistent with tumor flare, confirmed on a second scan >=6 weeks later that shows >=1 additional new lesion.
Time Frame	Up to 11 months

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Abiraterone Acetate	Placebo
Arm/Group Description:	Abiraterone acetate plus prednisone...	Placebo plus prednisone/prednisolon...
Arm/Group Description:	Abiraterone acetate plus prednisone/prednisolone administered as four 250 mg tablets of abiraterone acetate once daily plus 5 mg prednisone/5 mg prednisolone twice daily until disease progression.	Placebo plus prednisone/prednisolone administered as four placebo tablets once daily plus 5 mg prednisone/5 mg prednisolone tablet twice daily until disease progression.
Overall Number of Participants Analyzed	797	398
Median (95% Confidence Interval) Unit of Measure: Days
	171.0 (169.0 to 192.0)	110.0 (88.0 to 168.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abiraterone Acetate, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	The nominal P-value = 0.05.
	Method	Log Rank
	Comments	This was a stratified analysis.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.673
	Confidence Interval	(2-Sided) 95% 0.585 to 0.776
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	5 years
Adverse Event Reporting Description	Following interim analysis of the study by the Independent Data Monitoring Committee in August 2010, the protocol was amended to provide for the unblinding of all study participants and the option for placebo participants to receive abiraterone acetate treatment; 67 placebo participants crossed over.

Arm/Group Title	Abiraterone Acetate	Placebo	Placebo to Abiraterone Acetate
Arm/Group Description	Abiraterone acetate plus prednisone...	Placebo plus prednisone/prednisolon...	Placebo plus prednisone/prednisolon...
Arm/Group Description	Abiraterone acetate plus prednisone/prednisolone administered as four 250 mg tablets of abiraterone acetate once daily plus 5 mg prednisone/5 mg prednisolone twice daily until disease progression.	Placebo plus prednisone/prednisolone	Placebo plus prednisone/prednisolone crossed over to abiraterone acetate plus prednisone/prednisolone
All-Cause Mortality
	Abiraterone Acetate	Placebo	Placebo to Abiraterone Acetate
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Abiraterone Acetate	Placebo	Placebo to Abiraterone Acetate
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	365/791 (46.14%)	175/394 (44.42%)	29/67 (43.28%)
Blood and lymphatic system disorders
Anaemia ^† 1	26/791 (3.29%)	15/394 (3.81%)	1/67 (1.49%)
Coagulopathy ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Pancytopenia ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Thrombocytopenia ^† 1	6/791 (0.76%)	1/394 (0.25%)	0/67 (0.00%)
Febrile bone marrow aplasia ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Febrile neutropenia ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Neutropenia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Cardiac disorders
Bradycardia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Acute coronary syndrome ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Angina pectoris ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Atrial fibrillation ^† 1	6/791 (0.76%)	3/394 (0.76%)	1/67 (1.49%)
Atrioventricular block complete ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Cardiac failure ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Cardiac failure congestive ^† 1	4/791 (0.51%)	1/394 (0.25%)	0/67 (0.00%)
Cardio-respiratory arrest ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Cardiogenic shock ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Chest pain ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Left ventricular dysfunction ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Myocardial infarction ^† 1	7/791 (0.88%)	1/394 (0.25%)	0/67 (0.00%)
Pericardial effusion ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Supraventricular extrasystoles ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Supraventricular tachycardia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Tachycardia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Ear and labyrinth disorders
Hypoacusis ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Tinnitus ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Vertigo ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Endocrine disorders
Hyperglycaemia ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Adrenal insufficiency ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Adrenal suppression ^† 1	0/791 (0.00%)	0/394 (0.00%)	1/67 (1.49%)
Hyperthyroidism ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Eye disorders
Blindness ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Cataract ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Diplopia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Keratitis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Blindness unilateral ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Eye pain ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Pupils unequal ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Retinal vein occlusion ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Vitreous haemorrhage ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Gastrointestinal disorders
Constipation ^† 1	5/791 (0.63%)	3/394 (0.76%)	0/67 (0.00%)
Diarrhoea ^† 1	3/791 (0.38%)	2/394 (0.51%)	0/67 (0.00%)
Dysphagia ^† 1	1/791 (0.13%)	2/394 (0.51%)	0/67 (0.00%)
Enteritis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Faecaloma ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Gastritis ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Haematemesis ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Ileus ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Melaena ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Nausea ^† 1	8/791 (1.01%)	3/394 (0.76%)	0/67 (0.00%)
Oesophagitis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Subileus ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Vomiting ^† 1	17/791 (2.15%)	9/394 (2.28%)	1/67 (1.49%)
Abdominal pain ^† 1	6/791 (0.76%)	3/394 (0.76%)	0/67 (0.00%)
Anal fistula ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Colitis ischaemic ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Colonic obstruction ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Diverticular perforation ^† 1	1/791 (0.13%)	0/394 (0.00%)	1/67 (1.49%)
Gastrointestinal haemorrhage ^† 1	4/791 (0.51%)	0/394 (0.00%)	0/67 (0.00%)
Gastrointestinal obstruction ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Gastrooesophageal reflux disease ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Haemorrhoids ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Inguinal hernia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Intestinal obstruction ^† 1	1/791 (0.13%)	2/394 (0.51%)	1/67 (1.49%)
Intestinal perforation ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Pancreatitis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Pancreatitis acute ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Rectal haemorrhage ^† 1	3/791 (0.38%)	3/394 (0.76%)	0/67 (0.00%)
Small intestinal perforation ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Upper gastrointestinal haemorrhage ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
General disorders
Malaise ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Pain ^† 1	1/791 (0.13%)	6/394 (1.52%)	0/67 (0.00%)
Pyrexia ^† 1	6/791 (0.76%)	9/394 (2.28%)	3/67 (4.48%)
Asthenia ^† 1	9/791 (1.14%)	1/394 (0.25%)	0/67 (0.00%)
Catheter related complication ^† 1	0/791 (0.00%)	0/394 (0.00%)	1/67 (1.49%)
Chest pain ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Disease progression ^† 1	12/791 (1.52%)	2/394 (0.51%)	2/67 (2.99%)
Fatigue ^† 1	9/791 (1.14%)	6/394 (1.52%)	1/67 (1.49%)
General physical health deterioration ^† 1	5/791 (0.63%)	2/394 (0.51%)	0/67 (0.00%)
Generalised oedema ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Hernia obstructive ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Injection site haemorrhage ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Localised oedema ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Non-cardiac chest pain ^† 1	1/791 (0.13%)	2/394 (0.51%)	0/67 (0.00%)
Oedema peripheral ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Performance status decreased ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Hepatobiliary disorders
Cholecystitis ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Hepatitis ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Hepatotoxicity ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Hyperbilirubinaemia ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Bile duct obstruction ^† 1	2/791 (0.25%)	1/394 (0.25%)	0/67 (0.00%)
Cholecystitis acute ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Cholecystitis chronic ^† 1	0/791 (0.00%)	0/394 (0.00%)	1/67 (1.49%)
Infections and infestations
Bronchitis ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Cellulitis ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Cystitis ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Diverticulitis ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Gastroenteritis ^† 1	5/791 (0.63%)	0/394 (0.00%)	1/67 (1.49%)
Infection ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Meningitis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Parotitis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Pneumonia ^† 1	21/791 (2.65%)	5/394 (1.27%)	3/67 (4.48%)
Pyelonephritis ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Sepsis ^† 1	14/791 (1.77%)	2/394 (0.51%)	1/67 (1.49%)
Sinusitis ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Urosepsis ^† 1	4/791 (0.51%)	1/394 (0.25%)	0/67 (0.00%)
Abscess jaw ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Arthritis infective ^† 1	0/791 (0.00%)	0/394 (0.00%)	1/67 (1.49%)
Bacterial sepsis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Bronchopneumonia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Candida sepsis ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Catheter sepsis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Central line infection ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Enterocolitis infectious ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Escherichia infection ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Escherichia sepsis ^† 1	1/791 (0.13%)	0/394 (0.00%)	1/67 (1.49%)
Escherichia urinary tract infection ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Genitourinary tract infection ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Groin infection ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Herpes zoster ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Influenza ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Kidney infection ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Lobar pneumonia ^† 1	0/791 (0.00%)	3/394 (0.76%)	0/67 (0.00%)
Localised infection ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Lower respiratory tract infection ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Lung infection ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Osteomyelitis ^† 1	0/791 (0.00%)	0/394 (0.00%)	1/67 (1.49%)
Pelvic abscess ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Pneumonia escherichia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Post procedural infection ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Pyelonephritis acute ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Respiratory tract infection ^† 1	1/791 (0.13%)	2/394 (0.51%)	0/67 (0.00%)
Staphylococcal infection ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Tooth infection ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Urinary tract infection ^† 1	19/791 (2.40%)	3/394 (0.76%)	3/67 (4.48%)
Wound infection ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Injury, poisoning and procedural complications
Fall ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Accidental overdose ^† 1	0/791 (0.00%)	0/394 (0.00%)	1/67 (1.49%)
Ankle fracture ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Cervical vertebral fracture ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Concussion ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Cystitis radiation ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Dislocation of joint prosthesis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Drug toxicity ^† 1	0/791 (0.00%)	2/394 (0.51%)	0/67 (0.00%)
Femur fracture ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Foot fracture ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Gastroenteritis radiation ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Head injury ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Hip fracture ^† 1	5/791 (0.63%)	0/394 (0.00%)	0/67 (0.00%)
Humerus fracture ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Incisional hernia ^† 1	0/791 (0.00%)	0/394 (0.00%)	1/67 (1.49%)
Joint dislocation ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Lumbar vertebral fracture ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Medical device complication ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Pathological fracture ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Radiation associated pain ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Radius fracture ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Rib fracture ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Spinal compression fracture ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Spinal cord injury ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Spinal fracture ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Stent occlusion ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Subdural haematoma ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Tibia fracture ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Traumatic haematoma ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Upper limb fracture ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Urostomy complication ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Investigations
Alanine aminotransferase increased ^† 1	3/791 (0.38%)	1/394 (0.25%)	0/67 (0.00%)
Aspartate aminotransferase increased ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Blood alkaline phosphatase increased ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Blood creatinine increased ^† 1	4/791 (0.51%)	2/394 (0.51%)	0/67 (0.00%)
Blood phosphorus decreased ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Electrocardiogram QT prolonged ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Heart rate increased ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
International normalised ratio increased ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Liver function test abnormal ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Platelet count decreased ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Metabolism and nutrition disorders
Alkalosis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Anorexia ^† 1	4/791 (0.51%)	2/394 (0.51%)	0/67 (0.00%)
Dehydration ^† 1	14/791 (1.77%)	4/394 (1.02%)	1/67 (1.49%)
Gout ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Hyperglycaemia ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Hyperuricaemia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Hypocalcaemia ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Hypoglycaemia ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Hypokalaemia ^† 1	7/791 (0.88%)	0/394 (0.00%)	1/67 (1.49%)
Hyponatraemia ^† 1	4/791 (0.51%)	1/394 (0.25%)	0/67 (0.00%)
Hypophosphataemia ^† 1	2/791 (0.25%)	2/394 (0.51%)	0/67 (0.00%)
Diabetes mellitus ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Failure to thrive ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Hyperkalaemia ^† 1	1/791 (0.13%)	0/394 (0.00%)	1/67 (1.49%)
Hypomagnesaemia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	3/791 (0.38%)	4/394 (1.02%)	0/67 (0.00%)
Bursitis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Coccydynia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Myopathy ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Osteoarthritis ^† 1	2/791 (0.25%)	1/394 (0.25%)	0/67 (0.00%)
Osteonecrosis ^† 1	2/791 (0.25%)	0/394 (0.00%)	2/67 (2.99%)
Back pain ^† 1	12/791 (1.52%)	11/394 (2.79%)	4/67 (5.97%)
Bone lesion ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Bone pain ^† 1	16/791 (2.02%)	13/394 (3.30%)	1/67 (1.49%)
Flank pain ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Groin pain ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Intervertebral disc protrusion ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Mobility decreased ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Muscular weakness ^† 1	4/791 (0.51%)	1/394 (0.25%)	0/67 (0.00%)
Musculoskeletal chest pain ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Musculoskeletal pain ^† 1	3/791 (0.38%)	1/394 (0.25%)	0/67 (0.00%)
Neck pain ^† 1	3/791 (0.38%)	1/394 (0.25%)	1/67 (1.49%)
Osteoporotic fracture ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Pain in extremity ^† 1	4/791 (0.51%)	7/394 (1.78%)	2/67 (2.99%)
Pathological fracture ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Spinal column stenosis ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Spinal disorder ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Synovial cyst ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Cancer pain ^† 1	3/791 (0.38%)	1/394 (0.25%)	0/67 (0.00%)
Chronic lymphocytic leukaemia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Colon cancer ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Gastric cancer ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Malignant melanoma ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Malignant pleural effusion ^† 1	1/791 (0.13%)	0/394 (0.00%)	1/67 (1.49%)
Metastases to bone ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Metastases to central nervous system ^† 1	4/791 (0.51%)	1/394 (0.25%)	0/67 (0.00%)
Metastases to liver ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Metastases to lung ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Metastases to meninges ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Metastases to soft tissue ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Metastases to spine ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Metastatic pain ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Myelodysplastic syndrome ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Tumour pain ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Nervous system disorders
Convulsion ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Dizziness ^† 1	3/791 (0.38%)	1/394 (0.25%)	0/67 (0.00%)
Encephalopathy ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Epiduritis ^† 1	0/791 (0.00%)	2/394 (0.51%)	0/67 (0.00%)
Headache ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Hemiparesis ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Neuralgia ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Paraplegia ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Syncope ^† 1	3/791 (0.38%)	2/394 (0.51%)	0/67 (0.00%)
Brachial plexopathy ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Brain compression ^† 1	0/791 (0.00%)	2/394 (0.51%)	0/67 (0.00%)
Brain oedema ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Bulbar palsy ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Cauda equina syndrome ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Cerebral haemorrhage ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Cerebral ischaemia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Cerebrovascular accident ^† 1	4/791 (0.51%)	0/394 (0.00%)	0/67 (0.00%)
Cervical cord compression ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Cranial neuropathy ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Facial paresis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Hydrocephalus ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Loss of consciousness ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Lumbar radiculopathy ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Nerve root compression ^† 1	1/791 (0.13%)	1/394 (0.25%)	0/67 (0.00%)
Nerve root lesion ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Neurological symptom ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Neuropathy peripheral ^† 1	1/791 (0.13%)	2/394 (0.51%)	0/67 (0.00%)
Peroneal nerve palsy ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Polyneuropathy ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Radiculopathy ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Spinal cord compression ^† 1	23/791 (2.91%)	18/394 (4.57%)	3/67 (4.48%)
Subdural hygroma ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Syncope vasovagal ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Transient ischaemic attack ^† 1	4/791 (0.51%)	2/394 (0.51%)	0/67 (0.00%)
VIth nerve paralysis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Psychiatric disorders
Delirium ^† 1	1/791 (0.13%)	0/394 (0.00%)	1/67 (1.49%)
Depression ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Confusional state ^† 1	4/791 (0.51%)	3/394 (0.76%)	0/67 (0.00%)
Mental status changes ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Renal and urinary disorders
Anuria ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Dysuria ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Haematuria ^† 1	12/791 (1.52%)	11/394 (2.79%)	0/67 (0.00%)
Hydronephrosis ^† 1	12/791 (1.52%)	3/394 (0.76%)	2/67 (2.99%)
Polyuria ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Bladder stenosis ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Bladder tamponade ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Calculus ureteric ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Haemorrhage urinary tract ^† 1	3/791 (0.38%)	1/394 (0.25%)	0/67 (0.00%)
Nephrolithiasis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Obstructive uropathy ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Pollakiuria ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Renal failure ^† 1	4/791 (0.51%)	2/394 (0.51%)	0/67 (0.00%)
Renal failure acute ^† 1	7/791 (0.88%)	5/394 (1.27%)	2/67 (2.99%)
Renal impairment ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Stress urinary incontinence ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Ureteric obstruction ^† 1	3/791 (0.38%)	1/394 (0.25%)	1/67 (1.49%)
Urinary hesitation ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Urinary incontinence ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Urinary retention ^† 1	9/791 (1.14%)	6/394 (1.52%)	0/67 (0.00%)
Urinary tract obstruction ^† 1	0/791 (0.00%)	2/394 (0.51%)	0/67 (0.00%)
Reproductive system and breast disorders
Benign prostatic hyperplasia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Oedema genital ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Pelvic haematoma ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Pelvic pain ^† 1	2/791 (0.25%)	2/394 (0.51%)	0/67 (0.00%)
Respiratory, thoracic and mediastinal disorders
Asthma ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Dyspnoea ^† 1	11/791 (1.39%)	4/394 (1.02%)	1/67 (1.49%)
Pneumothorax ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Acute respiratory distress syndrome ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Acute respiratory failure ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Bronchial obstruction ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Chronic obstructive pulmonary disease ^† 1	1/791 (0.13%)	0/394 (0.00%)	1/67 (1.49%)
Epistaxis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Hypoxia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Pleural effusion ^† 1	2/791 (0.25%)	0/394 (0.00%)	2/67 (2.99%)
Pleuritic pain ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Pneumonia aspiration ^† 1	0/791 (0.00%)	2/394 (0.51%)	0/67 (0.00%)
Pulmonary embolism ^† 1	7/791 (0.88%)	10/394 (2.54%)	2/67 (2.99%)
Pulmonary oedema ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Respiratory distress ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Respiratory failure ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Skin and subcutaneous tissue disorders
Purpura ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Erythema ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Leukocytoclastic vasculitis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Skin ulcer ^† 1	2/791 (0.25%)	0/394 (0.00%)	0/67 (0.00%)
Surgical and medical procedures
Eye muscle recession ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Malignant tumour excision ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Pain management ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Ureteral stent insertion ^† 1	0/791 (0.00%)	1/394 (0.25%)	0/67 (0.00%)
Vascular disorders
Hypertension ^† 1	3/791 (0.38%)	0/394 (0.00%)	0/67 (0.00%)
Hypotension ^† 1	4/791 (0.51%)	1/394 (0.25%)	1/67 (1.49%)
Cardiovascular insufficiency ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Deep vein thrombosis ^† 1	5/791 (0.63%)	1/394 (0.25%)	0/67 (0.00%)
Embolism ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Hot flush ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Peripheral ischaemia ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Phlebitis ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
Superior vena caval occlusion ^† 1	1/791 (0.13%)	0/394 (0.00%)	0/67 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA Version 11.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Abiraterone Acetate	Placebo	Placebo to Abiraterone Acetate
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	766/791 (96.84%)	381/394 (96.70%)	57/67 (85.07%)
Blood and lymphatic system disorders
Anaemia ^† 1	202/791 (25.54%)	105/394 (26.65%)	11/67 (16.42%)
Gastrointestinal disorders
Constipation ^† 1	236/791 (29.84%)	124/394 (31.47%)	14/67 (20.90%)
Diarrhoea ^† 1	166/791 (20.99%)	57/394 (14.47%)	13/67 (19.40%)
Dyspepsia ^† 1	54/791 (6.83%)	15/394 (3.81%)	4/67 (5.97%)
Nausea ^† 1	272/791 (34.39%)	132/394 (33.50%)	19/67 (28.36%)
Vomiting ^† 1	204/791 (25.79%)	97/394 (24.62%)	14/67 (20.90%)
Abdominal pain ^† 1	111/791 (14.03%)	45/394 (11.42%)	4/67 (5.97%)
Dry mouth ^† 1	61/791 (7.71%)	20/394 (5.08%)	4/67 (5.97%)
General disorders
Pyrexia ^† 1	87/791 (11.00%)	28/394 (7.11%)	7/67 (10.45%)
Asthenia ^† 1	131/791 (16.56%)	54/394 (13.71%)	5/67 (7.46%)
Fatigue ^† 1	384/791 (48.55%)	172/394 (43.65%)	19/67 (28.36%)
Oedema peripheral ^† 1	228/791 (28.82%)	75/394 (19.04%)	11/67 (16.42%)
Pain ^† 1	40/791 (5.06%)	15/394 (3.81%)	2/67 (2.99%)
Infections and infestations
Nasopharyngitis ^† 1	58/791 (7.33%)	25/394 (6.35%)	6/67 (8.96%)
Upper respiratory tract infection ^† 1	57/791 (7.21%)	11/394 (2.79%)	2/67 (2.99%)
Urinary tract infection ^† 1	100/791 (12.64%)	27/394 (6.85%)	6/67 (8.96%)
Injury, poisoning and procedural complications
Contusion ^† 1	70/791 (8.85%)	22/394 (5.58%)	3/67 (4.48%)
Investigations
Weight decreased ^† 1	110/791 (13.91%)	57/394 (14.47%)	4/67 (5.97%)
Metabolism and nutrition disorders
Anorexia ^† 1	155/791 (19.60%)	74/394 (18.78%)	4/67 (5.97%)
Hyperglycaemia ^† 1	61/791 (7.71%)	20/394 (5.08%)	2/67 (2.99%)
Hypokalaemia ^† 1	149/791 (18.84%)	36/394 (9.14%)	10/67 (14.93%)
Decreased appetite ^† 1	89/791 (11.25%)	36/394 (9.14%)	4/67 (5.97%)
Dehydration ^† 1	43/791 (5.44%)	18/394 (4.57%)	2/67 (2.99%)
Hypomagnesaemia ^† 1	9/791 (1.14%)	3/394 (0.76%)	4/67 (5.97%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	246/791 (31.10%)	93/394 (23.60%)	20/67 (29.85%)
Back pain ^† 1	282/791 (35.65%)	138/394 (35.03%)	23/67 (34.33%)
Bone pain ^† 1	219/791 (27.69%)	112/394 (28.43%)	12/67 (17.91%)
Groin pain ^† 1	51/791 (6.45%)	22/394 (5.58%)	5/67 (7.46%)
Muscle spasms ^† 1	79/791 (9.99%)	37/394 (9.39%)	4/67 (5.97%)
Muscular weakness ^† 1	94/791 (11.88%)	38/394 (9.64%)	8/67 (11.94%)
Musculoskeletal pain ^† 1	140/791 (17.70%)	56/394 (14.21%)	12/67 (17.91%)
Myalgia ^† 1	50/791 (6.32%)	17/394 (4.31%)	6/67 (8.96%)
Neck pain ^† 1	35/791 (4.42%)	20/394 (5.08%)	4/67 (5.97%)
Pain in extremity ^† 1	170/791 (21.49%)	81/394 (20.56%)	13/67 (19.40%)
Nervous system disorders
Dizziness ^† 1	99/791 (12.52%)	40/394 (10.15%)	2/67 (2.99%)
Headache ^† 1	111/791 (14.03%)	42/394 (10.66%)	6/67 (8.96%)
Hypoaesthesia ^† 1	41/791 (5.18%)	15/394 (3.81%)	2/67 (2.99%)
Paraesthesia ^† 1	41/791 (5.18%)	15/394 (3.81%)	3/67 (4.48%)
Psychiatric disorders
Anxiety ^† 1	55/791 (6.95%)	21/394 (5.33%)	2/67 (2.99%)
Depression ^† 1	47/791 (5.94%)	21/394 (5.33%)	2/67 (2.99%)
Insomnia ^† 1	98/791 (12.39%)	52/394 (13.20%)	5/67 (7.46%)
Renal and urinary disorders
Haematuria ^† 1	76/791 (9.61%)	27/394 (6.85%)	2/67 (2.99%)
Nocturia ^† 1	54/791 (6.83%)	17/394 (4.31%)	4/67 (5.97%)
Pollakiuria ^† 1	61/791 (7.71%)	21/394 (5.33%)	4/67 (5.97%)
Urinary incontinence ^† 1	42/791 (5.31%)	15/394 (3.81%)	4/67 (5.97%)
Reproductive system and breast disorders
Pelvic pain ^† 1	20/791 (2.53%)	20/394 (5.08%)	2/67 (2.99%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	116/791 (14.66%)	33/394 (8.38%)	7/67 (10.45%)
Dyspnoea ^† 1	117/791 (14.79%)	49/394 (12.44%)	10/67 (14.93%)
Skin and subcutaneous tissue disorders
Ecchymosis ^† 1	17/791 (2.15%)	12/394 (3.05%)	4/67 (5.97%)
Hyperhidrosis ^† 1	44/791 (5.56%)	16/394 (4.06%)	1/67 (1.49%)
Vascular disorders
Hypertension ^† 1	79/791 (9.99%)	27/394 (6.85%)	5/67 (7.46%)
Hot flush ^† 1	157/791 (19.85%)	68/394 (17.26%)	2/67 (2.99%)
Hypotension ^† 1	35/791 (4.42%)	18/394 (4.57%)	4/67 (5.97%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA Version 11.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

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

The sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is at least 60 days from the time submitted to the sponsor for review. After 1) publication of multi-center results, 2) notification by sponsor that a multi-center submission is no longer planned, or 3) the 18 month anniversary of the termination of the study at all sites, the institution and investigator may publish or publicly present study data.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Senior Director, Clinical Research
Organization:	Johnson & Johnson Pharmaceutical Research & Development
Phone:	310-914-2915

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

Heller G, McCormack R, Kheoh T, Molina A, Smith MR, Dreicer R, Saad F, de Wit R, Aftab DT, Hirmand M, Limon A, Fizazi K, Fleisher M, de Bono JS, Scher HI. Circulating Tumor Cell Number as a Response Measure of Prolonged Survival for Metastatic Castration-Resistant Prostate Cancer: A Comparison With Prostate-Specific Antigen Across Five Randomized Phase III Clinical Trials. J Clin Oncol. 2018 Feb 20;36(6):572-580. doi: 10.1200/JCO.2017.75.2998. Epub 2017 Dec 22.

Chi KN, Kheoh T, Ryan CJ, Molina A, Bellmunt J, Vogelzang NJ, Rathkopf DE, Fizazi K, Kantoff PW, Li J, Azad AA, Eigl BJ, Heng DY, Joshua AM, de Bono JS, Scher HI. A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel. Ann Oncol. 2016 Mar;27(3):454-60. doi: 10.1093/annonc/mdv594. Epub 2015 Dec 18.

Fizazi K, Flaig TW, Stockle M, Scher HI, de Bono JS, Rathkopf DE, Ryan CJ, Kheoh T, Li J, Todd MB, Griffin TW, Molina A, Ohlmann CH. Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials. Ann Oncol. 2016 Apr;27(4):699-705. doi: 10.1093/annonc/mdv545. Epub 2015 Nov 25.

Antoun S, Bayar A, Ileana E, Laplanche A, Fizazi K, di Palma M, Escudier B, Albiges L, Massard C, Loriot Y. High subcutaneous adipose tissue predicts the prognosis in metastatic castration-resistant prostate cancer patients in post chemotherapy setting. Eur J Cancer. 2015 Nov;51(17):2570-7. doi: 10.1016/j.ejca.2015.07.042. Epub 2015 Aug 13.

Xu XS, Ryan CJ, Stuyckens K, Smith MR, Saad F, Griffin TW, Park YC, Yu MK, Vermeulen A, Poggesi I, Nandy P. Correlation between Prostate-Specific Antigen Kinetics and Overall Survival in Abiraterone Acetate-Treated Castration-Resistant Prostate Cancer Patients. Clin Cancer Res. 2015 Jul 15;21(14):3170-7. doi: 10.1158/1078-0432.CCR-14-1549. Epub 2015 Mar 31.

Scher HI, Heller G, Molina A, Attard G, Danila DC, Jia X, Peng W, Sandhu SK, Olmos D, Riisnaes R, McCormack R, Burzykowski T, Kheoh T, Fleisher M, Buyse M, de Bono JS. Circulating tumor cell biomarker panel as an individual-level surrogate for survival in metastatic castration-resistant prostate cancer. J Clin Oncol. 2015 Apr 20;33(12):1348-55. doi: 10.1200/JCO.2014.55.3487. Epub 2015 Mar 23.

Mulders PF, Molina A, Marberger M, Saad F, Higano CS, Chi KN, Li J, Kheoh T, Haqq CM, Fizazi K. Efficacy and safety of abiraterone acetate in an elderly patient subgroup (aged 75 and older) with metastatic castration-resistant prostate cancer after docetaxel-based chemotherapy. Eur Urol. 2014 May;65(5):875-83. doi: 10.1016/j.eururo.2013.09.005. Epub 2013 Sep 20.

Harland S, Staffurth J, Molina A, Hao Y, Gagnon DD, Sternberg CN, Cella D, Fizazi K, Logothetis CJ, Kheoh T, Haqq CM, de Bono JS, Scher HI; COU-AA-301 Investigators. Effect of abiraterone acetate treatment on the quality of life of patients with metastatic castration-resistant prostate cancer after failure of docetaxel chemotherapy. Eur J Cancer. 2013 Nov;49(17):3648-57. doi: 10.1016/j.ejca.2013.07.144. Epub 2013 Aug 22.

Ryan CJ, Molina A, Li J, Kheoh T, Small EJ, Haqq CM, Grant RP, de Bono JS, Scher HI. Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial. J Clin Oncol. 2013 Aug 1;31(22):2791-8. doi: 10.1200/JCO.2012.45.4595. Epub 2013 Jul 1.

Logothetis CJ, Basch E, Molina A, Fizazi K, North SA, Chi KN, Jones RJ, Goodman OB, Mainwaring PN, Sternberg CN, Efstathiou E, Gagnon DD, Rothman M, Hao Y, Liu CS, Kheoh TS, Haqq CM, Scher HI, de Bono JS. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol. 2012 Dec;13(12):1210-7. doi: 10.1016/S1470-2045(12)70473-4. Epub 2012 Nov 9.

Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, Staffurth JN, North S, Vogelzang NJ, Saad F, Mainwaring P, Harland S, Goodman OB Jr, Sternberg CN, Li JH, Kheoh T, Haqq CM, de Bono JS; COU-AA-301 Investigators. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012 Oct;13(10):983-92. doi: 10.1016/S1470-2045(12)70379-0. Epub 2012 Sep 18. Erratum In: Lancet Oncol. 2012 Nov;13(11):e464. Lancet Oncol. 2014 Aug;15(9):e365.

de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Flechon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI; COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011 May 26;364(21):1995-2005. doi: 10.1056/NEJMoa1014618.

Layout table for additonal information

Responsible Party:	Cougar Biotechnology, Inc.
ClinicalTrials.gov Identifier:	NCT00638690
Other Study ID Numbers:	CR016924 COU-AA-301 ( Other Identifier: Cougar Biotechnology, Inc )
First Submitted:	March 13, 2008
First Posted:	March 19, 2008
Results First Submitted:	August 23, 2011
Results First Posted:	May 16, 2013
Last Update Posted:	April 30, 2014

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