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Radium-223 Dichloride and Abiraterone Acetate Compared to Placebo and Abiraterone Acetate for Men With Cancer of the Prostate When Medical or Surgical Castration Does Not Work and When the Cancer Has Spread to the Bone, Has Not Been Treated With Chemotherapy and is Causing no or Only Mild Symptoms (ERA 223)

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ClinicalTrials.gov Identifier: NCT02043678
Recruitment Status : Active, not recruiting
First Posted : January 23, 2014
Results First Posted : March 5, 2019
Last Update Posted : May 11, 2021
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Bayer

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: Radium-223 dichloride (Xofigo, BAY88-8223)
Drug: Matching placebo (normal saline)
Drug: Abiraterone
Drug: Prednisone/Prednisolone
Enrollment 806
Recruitment Details Study was conducted at multiple centers in 19 countries between 30 March 2014 (first participant first visit) and 31 October 2019 (data cut-off date).
Pre-assignment Details Overall, 1144 participants were screened. Of them, 338 participants did not complete screening, 806 participants were randomized to treatment and 786 participants received study treatment.
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met). Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Period Title: Overall Study
Started 401 405
Treated 390 396
Completed [1] 0 0
Not Completed 401 405
Reason Not Completed
Never treated             11             9
AE with clinical progressive disease(PD)             18             18
AE without clinical PD             51             34
Lost to Follow-up             1             1
Other             19             16
Clinical PD             108             138
Radiological PD             91             80
Protocol-driven decision point             56             56
Withdrawal by Subject             12             15
Ongoing with treatment             34             38
[1]
Completed treatment
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred Total
Hide Arm/Group Description Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met). Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met). Total of all reporting groups
Overall Number of Baseline Participants 401 405 806
Hide Baseline Analysis Population Description
Intent-to-treat analysis set (ITT) included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 401 participants 405 participants 806 participants
70.9  (8.5) 71.4  (8.4) 71.1  (8.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 401 participants 405 participants 806 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
401
 100.0%
405
 100.0%
806
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 401 participants 405 participants 806 participants
Hispanic or Latino
17
   4.2%
23
   5.7%
40
   5.0%
Not Hispanic or Latino
361
  90.0%
355
  87.7%
716
  88.8%
Unknown or Not Reported
23
   5.7%
27
   6.7%
50
   6.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 401 participants 405 participants 806 participants
American Indian or Alaska Native
1
   0.2%
1
   0.2%
2
   0.2%
Asian
79
  19.7%
78
  19.3%
157
  19.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
10
   2.5%
16
   4.0%
26
   3.2%
White
285
  71.1%
284
  70.1%
569
  70.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
26
   6.5%
26
   6.4%
52
   6.5%
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)
Number Analyzed 396 participants 400 participants 796 participants
82.19  (16.75) 82.40  (16.01) 82.30  (16.37)
[1]
Measure Analysis Population Description: ITT analysis set with evaluable number of participants
Stage of prostate cancer at diagnosis (Tumor Node Metastasis [TNM] Classification)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 401 participants 405 participants 806 participants
Missing
19
   4.7%
24
   5.9%
43
   5.3%
Stage I
27
   6.7%
18
   4.4%
45
   5.6%
Stage IIA
22
   5.5%
20
   4.9%
42
   5.2%
Stage IIB
34
   8.5%
49
  12.1%
83
  10.3%
Stage III
102
  25.4%
88
  21.7%
190
  23.6%
Stage IV
197
  49.1%
206
  50.9%
403
  50.0%
[1]
Measure Description: TNM staging system stands for Tumour, Node, Metastasis. Stage I: cancer is in half of one side of the prostate or less. Stage II: cancer is in more than half of one side of the prostate, completely contained within the prostate gland. Stage III: cancer has broken through the capsule of the prostate gland, and may have spread into tubes that carry semen. Stage IV: cancer has spread into nearby body organs, such as the back passage or bladder; or has spread to nearby lymph nodes; or has spread to other parts of the body outside the pelvis, such as the lungs or liver.
Cancer pain assessment by Brief Pain Inventory-Short Form (BPI-SF)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 401 participants 405 participants 806 participants
Missing
25
   6.2%
33
   8.1%
58
   7.2%
Asymptomatic (Worst pain score = 0)
195
  48.6%
198
  48.9%
393
  48.8%
Mildly Symptomatic (Worst pain score 1 - 3)
181
  45.1%
174
  43.0%
355
  44.0%
[1]
Measure Description: The BPI-SF is a short, self-administered questionnaire with 11 items designed to evaluate the intensity of, and the impairment caused by pain. Four items measure pain intensity (pain now, average pain, worst pain, and least pain) using 0 ("no pain") to 10 ("pain as bad as you can imagine") numeric rating scales, and 7 items measure the level of interference with function caused by pain (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life) using 0 (no interference) to 10 (complete interference) rating scales.
Gleason score at diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 401 participants 405 participants 806 participants
Missing
15
   3.7%
18
   4.4%
33
   4.1%
Less than (<) 8
140
  34.9%
154
  38.0%
294
  36.5%
Greater than or equal to (>=) 8
246
  61.3%
233
  57.5%
479
  59.4%
[1]
Measure Description: The Gleason score is an indication of prognosis based on prostate pathology. The total score ranges from 2 to 10 (ie: "1+1" to "5+5") with a higher score reflecting less-differentiated tumors with worse prognosis. The total score is a sum of two numbers which are based on the microscopic appearance of cells. The first number is the score based on the dominant, cell morphology (scored 1-5) and the second number is based on the highest grade of the non-dominant cell pattern (scored 1-5).
Prostate-specific antigen   [1] 
Mean (Standard Deviation)
Unit of measure:  Micrograms per liter (ug/L)
Number Analyzed 396 participants 401 participants 797 participants
92.39  (191.62) 92.33  (328.00) 92.36  (268.85)
[1]
Measure Analysis Population Description: ITT set with evaluable number of participants.
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 401 participants 405 participants 806 participants
Missing
2
   0.5%
3
   0.7%
5
   0.6%
0
262
  65.3%
281
  69.4%
543
  67.4%
1
137
  34.2%
121
  29.9%
258
  32.0%
[1]
Measure Description: Eastern cooperative oncology group (ECOG) performance status: 0= Fully active, able to carry on all pre-disease performance without restriction; 1= Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2= Ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3= Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4= Completely disabled, cannot carry on any self-care, totally confined to bed or chair.
Extent of Disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 401 participants 405 participants 806 participants
Normal or abnormal because of benign bone disease
2
   0.5%
0
   0.0%
2
   0.2%
< 6 metastases
134
  33.4%
141
  34.8%
275
  34.1%
6-20 metastases
175
  43.6%
181
  44.7%
356
  44.2%
>20 lesions but not a superscan
71
  17.7%
70
  17.3%
141
  17.5%
Superscan
19
   4.7%
13
   3.2%
32
   4.0%
1.Primary Outcome
Title Symptomatic Skeletal Event Free Survival (SSE-FS)
Hide Description SSE-FS was defined as time (months) from randomization to the earliest of onset date of skeletal symptoms treated with external beam radiotherapy (EBRT), onset date of pathological bone fracture, onset date of spinal cord compression, procedure date of tumor-related orthopedic surgery, or death from any cause. Subjects who died without prior SSE and ≥ 13 weeks after the last SSE assessment are censored at the last SSE assessment date. Subjects alive at the survival cut-off date are censored at the last date known to be alive. Subjects with multiple events are only counted for the category in which the first event occurred. If multiple SSE (component events) occur on the same date for 1 subject, the subject is only counted into 1 category in the order of: spinal cord compression > bone fracture > orthopedic surgery > EBRT.
Time Frame From randomization until first onset of on-study symptomatic skeletal event (SSE) or death, up to 47 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) analysis set (included all randomized participants)
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 401 405
Median (95% Confidence Interval)
Unit of Measure: Months
22.3
(20.4 to 24.8)
26.0
(21.8 to 28.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Radium-223 Dichloride + Abi/Pred, Placebo + Abi/Pred
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2636
Comments [Not Specified]
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.122
Confidence Interval (2-Sided) 95%
0.917 to 1.374
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time (months) from the date of randomization to the date of death due to any cause. Subjects alive at the survival cut-off date were censored at the last date known to be alive.
Time Frame From randomization until death from any cause, up to 67 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set (included all randomized participants)
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 401 405
Median (95% Confidence Interval)
Unit of Measure: Months
30.1
(27.5 to 33.2)
34.8
(31.5 to 37.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Radium-223 Dichloride + Abi/Pred, Placebo + Abi/Pred
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1194
Comments [Not Specified]
Method Cox Proportional Hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.151
Confidence Interval (2-Sided) 95%
0.964 to 1.374
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Radiological Progression Free Survival (rPFS)
Hide Description rPFS was defined as the time (months) from the date of randomization to the date of confirmed radiological progression or death (if death occurred before progression) based on independent assessment.
Time Frame From randomization until the date of confirmed radiological progression or death, up to 47 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set (included all randomized participants)
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 401 405
Median (95% Confidence Interval)
Unit of Measure: Months
11.2
(9.1 to 11.8)
12.4
(10.8 to 14.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Radium-223 Dichloride + Abi/Pred, Placebo + Abi/Pred
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1283
Comments [Not Specified]
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.152
Confidence Interval (2-Sided) 95%
0.960 to 1.383
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to Pain Progression
Hide Description Time to pain progression was defined as the interval from randomization to the first date a subject experienced pain progression, assessed by BPI-SF (see Baseline Characteristics) and defined as: an increase of 2 or more points in the average worst pain score (WPS) from baseline observed at 2 consecutive evaluations >= 4 weeks apart or initiation of short- or long-acting opioid use for pain for subjects with WPS 0 at baseline; an increase of 2 or more points in the average WPS from baseline observed at 2 consecutive evaluations ≥ 4 weeks apart and an average WPS of ≥ 4 OR initiation of short- or long-acting opioid use for pain for subjects with WPS 1 to 3 at baseline. Subjects without pain progression at the end of study are censored at the last date known to have not progressed: the last evaluation date for pain scores or last visit when recorded opiate use, whichever is last. Subjects with no on-study assessment or no baseline assessment are censored at the date of randomization.
Time Frame From randomization until the date of pain progression based on pain score, up to 47 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set (included all randomized participants)
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 401 405
Median (95% Confidence Interval)
Unit of Measure: Months
14.4
(11.1 to 20.1)
18.7
(15.4 to 23.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Radium-223 Dichloride + Abi/Pred, Placebo + Abi/Pred
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1669
Comments [Not Specified]
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.145
Confidence Interval (2-Sided) 95%
0.945 to 1.389
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time to Cytotoxic Chemotherapy
Hide Description Time to cytotoxic chemotherapy is time (months) from randomization to the earliest date of the first cytotoxic chemotherapy. Participants who have not started cytotoxic chemotherapy during the study were censored at the last assessment date.
Time Frame From randomization until the date of first cytotoxic chemotherapy, up to 47 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set (included all randomized participants)
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 401 405
Median (95% Confidence Interval)
Unit of Measure: Months
29.5
(26.5 to 35.7)
28.5 [1] 
(23.7 to NA)
[1]
Upper limit cannot be estimated due to censored data.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Radium-223 Dichloride + Abi/Pred, Placebo + Abi/Pred
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7871
Comments [Not Specified]
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.033
Confidence Interval (2-Sided) 95%
0.816 to 1.308
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to Opiate Use for Cancer Pain
Hide Description Time to opiate use for cancer pain was defined as the interval from the date of randomization to the date of opiate use.
Time Frame From randomization until the date of opiate use, up to 47 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set excluding participants who had opiate use at baseline
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 398 392
Median (95% Confidence Interval)
Unit of Measure: Months
19.0
(14.4 to 23.2)
22.6
(18.0 to 25.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Radium-223 Dichloride + Abi/Pred, Placebo + Abi/Pred
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2467
Comments [Not Specified]
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.126
Confidence Interval (2-Sided) 95%
0.921 to 1.378
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events
Hide Description An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a participant in the study. A serious adverse event (SAE) was any untoward medical occurrence that at any dose was resulting in death, was lifethreatening, requires hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity. AEs or SAEs occurring after start of study treatment until the end of the treatment period were defined as treatment-emergent AEs (TEAEs) or serious TEAEs. Drug-related TEAEs or serious TEAEs were those with "reasonable causal relationship" to the study treatment decided by the investigators.
Time Frame From start of study treatment until the end of the treatment period, up to 65 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set (SAF): included all randomized subjects who received at least one dose of any study drug
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 392 394
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
382
  97.4%
387
  98.2%
Any drug-related TEAE
265
  67.6%
271
  68.8%
Radium-223/Placebo-related TEAE
92
  23.5%
92
  23.4%
Any serious TEAE
175
  44.6%
172
  43.7%
Any drug-related serious TEAE
32
   8.2%
29
   7.4%
Radium-223/Placebo-related serious TEAE
11
   2.8%
7
   1.8%
8.Secondary Outcome
Title Number of Subjects With Radium-223/Placebo-related Treatment-emergent Adverse Events Per Maximum Intensity
Hide Description An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a participant in the study. A serious adverse event (SAE) was any untoward medical occurrence that at any dose was resulting in death, was lifethreatening, requires hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity. AEs or SAEs occurring after start of study treatment until the end of the treatment period were defined as treatment-emergent AEs (TEAEs) or serious TEAEs. Radium-223/placebo-related TEAEs or serious TEAEs were those with "reasonable causal relationship" to radium-223 or placebo decided by the investigators.
Time Frame From start of study treatment until the end of the treatment period, up to 65 months
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Hide Analysis Population Description
Safety analysis set (SAF): included all randomized subjects who received at least one dose of any study drug
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 392 394
Measure Type: Count of Participants
Unit of Measure: Participants
TEAE - Grade 1
44
  11.2%
53
  13.5%
TEAE - Grade 2
28
   7.1%
24
   6.1%
TEAE - Grade 3
19
   4.8%
13
   3.3%
TEAE - Grade 4
1
   0.3%
2
   0.5%
Serious TEAE - Grade 2
3
   0.8%
0
   0.0%
Serious TEAE - Grade 3
8
   2.0%
5
   1.3%
Serious TEAE - Grade 4
0
   0.0%
2
   0.5%
9.Secondary Outcome
Title Number of Participants With Any Treatment-emergent Additional Primary Malignancies
Hide Description Treatment-emergent additional primary malignancies were adverse events identified as additional primary malignancies that occurred after start of study treatment until the end of the treatment period.
Time Frame From start of study treatment until 4 weeks after last study treatment, up to 65 months
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Hide Analysis Population Description
Safety analysis set (SAF): included all randomized subjects who received at least one dose of any study drug
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 392 394
Measure Type: Count of Participants
Unit of Measure: Participants
26
   6.6%
25
   6.3%
10.Secondary Outcome
Title Number of Participants With Treatment-emergent Bone Fractures
Hide Description Treatment-emergent fractures were adverse events identified as fractures that occurred after start of study treatment until the end of the treatment period. All bone fractures and bone-associated events (e.g., osteoporosis) were reported as either AEs, or SAEs if the criteria of SAE were met, regardless of the investigator's causality assessment.
Time Frame From start of study treatment until 4 weeks after last study treatment, up to 65 months
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Hide Analysis Population Description
Safety analysis set (SAF): included all randomized subjects who received at least one dose of any study drug
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 392 394
Measure Type: Count of Participants
Unit of Measure: Participants
107
  27.3%
49
  12.4%
11.Secondary Outcome
Title Number of Participants With Post-treatment Adverse Events
Hide Description An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a participant in the study. Any bleeding event occurring during the study was not documented as an AE because this event was planned to be captured in the assessment of efficacy. AEs that started after the treatment period were defined as post-treatment AEs. Drug-related AEs were those with "reasonable causal relationship" to the study treatment decided by the investigators.
Time Frame After the treatment period, up to 46 months
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Hide Analysis Population Description
Safety analysis set (SAF): included all randomized subjects who received at least one dose of any study drug
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 392 394
Measure Type: Count of Participants
Unit of Measure: Participants
Any events
138
  35.2%
133
  33.8%
Any drug-related events
18
   4.6%
9
   2.3%
Any chemotherapy-related events
31
   7.9%
34
   8.6%
Any additional primary malignancies
6
   1.5%
7
   1.8%
12.Secondary Outcome
Title Number of Participants With Any Study Drug-related Post-treatment Adverse Events Per Maximum Intensity
Hide Description An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a participant in the study. Any bleeding event occurring during the study was not documented as an AE because this event was planned to be captured in the assessment of efficacy. AEs that started after the treatment period were defined as post-treatment AEs. Drug-related AEs were those with "reasonable causal relationship" to the study treatment decided by the investigators.
Time Frame After the treatment period, up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set (SAF): included all randomized subjects who received at least one dose of any study drug
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 392 394
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
3
   0.8%
3
   0.8%
Grade 2
9
   2.3%
3
   0.8%
Grade 3
5
   1.3%
3
   0.8%
Grade 4
1
   0.3%
0
   0.0%
13.Secondary Outcome
Title Number of Participants With Post-treatment Chemotherapy-related Blood and Lymphatic System Disorders
Hide Description Post-treatment blood and lymphatic system disorders were adverse events identified as blood and lymphatic system disorders that occurred after the end of the treatment period until participant died, was lost to follow-up, withdrew informed consent, actively objected to collection of further data, or was transitioned to the extended safety follow-up study.
Time Frame After the treatment period, up to 46 months
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Hide Analysis Population Description
Safety analysis set (SAF): included all randomized subjects who received at least one dose of any study drug
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 392 394
Measure Type: Count of Participants
Unit of Measure: Participants
Anaemia
5
   1.3%
4
   1.0%
Bone marrow failure
1
   0.3%
0
   0.0%
Febrile neutropenia
5
   1.3%
8
   2.0%
Leukopenia
1
   0.3%
0
   0.0%
Neutropenia
8
   2.0%
3
   0.8%
Pancytopenia
0
   0.0%
1
   0.3%
Thrombocytopenia
2
   0.5%
2
   0.5%
14.Secondary Outcome
Title Number of Participants With Post-treatment Bone Fractures
Hide Description Post-treatment fractures were adverse events identified as fractures that occured after the end of the treatment period until participant died, was lost to follow-up, withdrew informed consent, actively objected to collection of further data, or was transitioned to the extended safety follow-up study. All bone fractures and bone-associated events (e.g., osteoporosis), were reported as either AEs, or SAEs if the criteria of SAE were met, regardless of the investigator's causality assessment.
Time Frame After the treatment period, up to 46 months
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Hide Analysis Population Description
Safety analysis set (SAF): included all randomized subjects who received at least one dose of any study drug
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description:
Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met).
Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
Overall Number of Participants Analyzed 392 394
Measure Type: Count of Participants
Unit of Measure: Participants
Lumbar vertebral fracture
0
   0.0%
1
   0.3%
Rib fracture
0
   0.0%
1
   0.3%
Spinal compression fracture
0
   0.0%
1
   0.3%
Thoracic vertebral fracture
0
   0.0%
1
   0.3%
Traumatic fracture
6
   1.5%
2
   0.5%
Osteoporotic fracture
6
   1.5%
0
   0.0%
Pathological fracture
12
   3.1%
13
   3.3%
Time Frame From start of study treatment to cut-off date 31-OCT-2019, which is about 67 months.
Adverse Event Reporting Description Adverse events (AEs) included any event arising or worsening from the start of the study treatment. All occurrences of additional malignancies, chemotherapy-related events, bone fractures and bone associated events were reported as AE regardless of the investigator's causality assessment.
 
Arm/Group Title Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Hide Arm/Group Description Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met). Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met).
All-Cause Mortality
Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Affected / at Risk (%) Affected / at Risk (%)
Total   254/392 (64.80%)      242/394 (61.42%)    
Hide Serious Adverse Events
Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   190/392 (48.47%)      185/394 (46.95%)    
Blood and lymphatic system disorders     
Anaemia * 1  9/392 (2.30%)  19 4/394 (1.02%)  5
Disseminated intravascular coagulation * 1  0/392 (0.00%)  0 1/394 (0.25%)  2
Febrile neutropenia * 1  3/392 (0.77%)  3 6/394 (1.52%)  6
Leukopenia * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Lymphopenia * 1  1/392 (0.26%)  6 0/394 (0.00%)  0
Neutropenia * 1  2/392 (0.51%)  2 1/394 (0.25%)  1
Pancytopenia * 1  0/392 (0.00%)  0 2/394 (0.51%)  2
Thrombocytopenia * 1  3/392 (0.77%)  9 0/394 (0.00%)  0
Bone marrow failure * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Cardiac disorders     
Acute myocardial infarction * 1  5/392 (1.28%)  6 4/394 (1.02%)  4
Aortic valve incompetence * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Aortic valve stenosis * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Arrhythmia * 1  0/392 (0.00%)  0 1/394 (0.25%)  2
Atrial fibrillation * 1  4/392 (1.02%)  5 8/394 (2.03%)  8
Atrial flutter * 1  1/392 (0.26%)  2 1/394 (0.25%)  1
Atrioventricular block complete * 1  2/392 (0.51%)  3 0/394 (0.00%)  0
Cardiac arrest * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Cardiac failure * 1  1/392 (0.26%)  2 3/394 (0.76%)  6
Cardiac failure congestive * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Cardio-respiratory arrest * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Coronary artery stenosis * 1  0/392 (0.00%)  0 2/394 (0.51%)  2
Coronary ostial stenosis * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Myocardial infarction * 1  3/392 (0.77%)  4 1/394 (0.25%)  1
Sinus bradycardia * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Ventricular fibrillation * 1  1/392 (0.26%)  2 1/394 (0.25%)  2
Ventricular tachycardia * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Acute coronary syndrome * 1  2/392 (0.51%)  2 0/394 (0.00%)  0
Cardiac disorder * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Congenital, familial and genetic disorders     
Inborn error of metabolism * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Ear and labyrinth disorders     
Vertigo * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Endocrine disorders     
Primary adrenal insufficiency * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Eye disorders     
Cataract * 1  1/392 (0.26%)  1 2/394 (0.51%)  2
Retinal artery occlusion * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Abdominal pain lower * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Constipation * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Diarrhoea * 1  3/392 (0.77%)  3 5/394 (1.27%)  5
Diverticulum intestinal haemorrhagic * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Duodenal ulcer * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Dysphagia * 1  2/392 (0.51%)  2 0/394 (0.00%)  0
Enterocolitis * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Gastric haemorrhage * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Gastric ulcer * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Gastrointestinal disorder * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Gastrointestinal haemorrhage * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Ileus * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Incarcerated inguinal hernia * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Inguinal hernia * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Large intestine perforation * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Nausea * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Oesophageal achalasia * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Oesophageal ulcer * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Rectal haemorrhage * 1  0/392 (0.00%)  0 2/394 (0.51%)  2
Small intestinal obstruction * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Small intestinal perforation * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Vomiting * 1  3/392 (0.77%)  3 2/394 (0.51%)  2
Lower gastrointestinal haemorrhage * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Large intestine polyp * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Anal prolapse * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
General disorders     
Asthenia * 1  1/392 (0.26%)  2 4/394 (1.02%)  6
Death * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Fatigue * 1  2/392 (0.51%)  2 2/394 (0.51%)  2
Influenza like illness * 1  0/392 (0.00%)  0 1/394 (0.25%)  2
Malaise * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Oedema peripheral * 1  2/392 (0.51%)  2 1/394 (0.25%)  1
Pain * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Pyrexia * 1  5/392 (1.28%)  5 4/394 (1.02%)  4
Sudden death * 1  0/392 (0.00%)  0 2/394 (0.51%)  2
Peripheral swelling * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
General physical health deterioration * 1  10/392 (2.55%)  14 13/394 (3.30%)  19
Physical deconditioning * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Non-cardiac chest pain * 1  2/392 (0.51%)  2 1/394 (0.25%)  1
Multiple organ dysfunction syndrome * 1  2/392 (0.51%)  2 0/394 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis * 1  0/392 (0.00%)  0 1/394 (0.25%)  2
Cholecystitis acute * 1  1/392 (0.26%)  1 2/394 (0.51%)  2
Hepatic function abnormal * 1  0/392 (0.00%)  0 1/394 (0.25%)  2
Bile duct obstruction * 1  1/392 (0.26%)  2 0/394 (0.00%)  0
Hepatobiliary disease * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Infections and infestations     
Acute sinusitis * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Appendicitis * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Bacteraemia * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Bronchitis * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Cellulitis * 1  3/392 (0.77%)  3 2/394 (0.51%)  2
Clostridium difficile colitis * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Diverticulitis * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Encephalitis * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Erysipelas * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Gastroenteritis * 1  3/392 (0.77%)  3 2/394 (0.51%)  2
Gastroenteritis clostridial * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Gastrointestinal infection * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Infection * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Influenza * 1  1/392 (0.26%)  1 2/394 (0.51%)  2
Lower respiratory tract infection * 1  2/392 (0.51%)  2 1/394 (0.25%)  1
Lyme disease * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Osteomyelitis * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Pneumonia * 1  12/392 (3.06%)  15 16/394 (4.06%)  20
Pulmonary tuberculosis * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Sepsis * 1  2/392 (0.51%)  4 4/394 (1.02%)  7
Septic shock * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Sinusitis * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Skin infection * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Upper respiratory tract infection * 1  0/392 (0.00%)  0 5/394 (1.27%)  6
Urinary tract infection * 1  18/392 (4.59%)  21 10/394 (2.54%)  12
Viral upper respiratory tract infection * 1  0/392 (0.00%)  0 2/394 (0.51%)  3
Wound infection * 1  1/392 (0.26%)  3 0/394 (0.00%)  0
Urosepsis * 1  1/392 (0.26%)  1 6/394 (1.52%)  12
Tooth infection * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Acute endocarditis * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Neutropenic sepsis * 1  2/392 (0.51%)  2 0/394 (0.00%)  0
Groin infection * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Pulmonary sepsis * 1  2/392 (0.51%)  4 1/394 (0.25%)  1
Arthritis bacterial * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Clostridium difficile infection * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Infective exacerbation of chronic obstructive airways disease * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Staphylococcal infection * 1  0/392 (0.00%)  0 1/394 (0.25%)  2
Pneumonia bacterial * 1  0/392 (0.00%)  0 1/394 (0.25%)  2
Arthritis infective * 1  1/392 (0.26%)  2 0/394 (0.00%)  0
Respiratory tract infection * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Encephalitis fungal * 1  1/392 (0.26%)  2 0/394 (0.00%)  0
Gastroenteritis norovirus * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Large intestine infection * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Injury, poisoning and procedural complications     
Alcohol poisoning * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Fall * 1  0/392 (0.00%)  0 3/394 (0.76%)  3
Femoral neck fracture * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Femur fracture * 1  0/392 (0.00%)  0 2/394 (0.51%)  2
Humerus fracture * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Joint dislocation * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Pneumothorax traumatic * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Radius fracture * 1  0/392 (0.00%)  0 1/394 (0.25%)  2
Soft tissue injury * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Spinal compression fracture * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Subdural haematoma * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Ulna fracture * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Traumatic fracture * 1  13/392 (3.32%)  19 5/394 (1.27%)  5
Lumbar vertebral fracture * 1  1/392 (0.26%)  2 0/394 (0.00%)  0
Brain contusion * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Pseudophakic bullous keratopathy * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Investigations     
Alanine aminotransferase increased * 1  2/392 (0.51%)  6 1/394 (0.25%)  1
Aspartate aminotransferase increased * 1  2/392 (0.51%)  5 1/394 (0.25%)  1
Blood bilirubin increased * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Blood lactate dehydrogenase increased * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Platelet count decreased * 1  1/392 (0.26%)  1 1/394 (0.25%)  3
Weight decreased * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Influenza A virus test positive * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Metabolism and nutrition disorders     
Dehydration * 1  4/392 (1.02%)  4 1/394 (0.25%)  1
Diabetes mellitus * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Hypercalcaemia * 1  0/392 (0.00%)  0 1/394 (0.25%)  3
Hyperglycaemia * 1  1/392 (0.26%)  1 2/394 (0.51%)  3
Hypokalaemia * 1  2/392 (0.51%)  3 1/394 (0.25%)  3
Hyponatraemia * 1  1/392 (0.26%)  2 2/394 (0.51%)  11
Iron deficiency * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Decreased appetite * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Hypophagia * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  3/392 (0.77%)  3 2/394 (0.51%)  2
Back pain * 1  8/392 (2.04%)  10 11/394 (2.79%)  12
Bone pain * 1  7/392 (1.79%)  8 5/394 (1.27%)  8
Bursitis * 1  0/392 (0.00%)  0 1/394 (0.25%)  2
Lumbar spinal stenosis * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Muscular weakness * 1  3/392 (0.77%)  4 2/394 (0.51%)  3
Musculoskeletal pain * 1  1/392 (0.26%)  1 1/394 (0.25%)  2
Neck pain * 1  1/392 (0.26%)  1 2/394 (0.51%)  2
Osteoarthritis * 1  1/392 (0.26%)  1 2/394 (0.51%)  2
Osteonecrosis * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Osteoporosis * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Osteoporotic fracture * 1  9/392 (2.30%)  14 1/394 (0.25%)  3
Pain in extremity * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Pathological fracture * 1  8/392 (2.04%)  13 4/394 (1.02%)  4
Rhabdomyolysis * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Spinal osteoarthritis * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Mobility decreased * 1  1/392 (0.26%)  2 0/394 (0.00%)  0
Intervertebral disc protrusion * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Osteonecrosis of jaw * 1  3/392 (0.77%)  3 1/394 (0.25%)  1
Spinal pain * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma gastric * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Adenocarcinoma of colon * 1  1/392 (0.26%)  3 1/394 (0.25%)  1
Anaplastic thyroid cancer * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
B-cell lymphoma * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Basal cell carcinoma * 1  3/392 (0.77%)  8 6/394 (1.52%)  12
Bladder cancer * 1  1/392 (0.26%)  1 2/394 (0.51%)  3
Bladder cancer recurrent * 1  1/392 (0.26%)  1 2/394 (0.51%)  6
Bladder transitional cell carcinoma * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Bowen's disease * 1  1/392 (0.26%)  1 2/394 (0.51%)  2
Bronchial carcinoma * 1  1/392 (0.26%)  2 0/394 (0.00%)  0
Cholangiocarcinoma * 1  0/392 (0.00%)  0 1/394 (0.25%)  2
Chronic lymphocytic leukaemia * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Colon cancer * 1  3/392 (0.77%)  3 1/394 (0.25%)  1
Gastric cancer * 1  1/392 (0.26%)  1 1/394 (0.25%)  3
Kaposi's sarcoma * 1  1/392 (0.26%)  2 0/394 (0.00%)  0
Lung adenocarcinoma * 1  2/392 (0.51%)  2 1/394 (0.25%)  1
Malignant melanoma * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Meningioma * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Nasal sinus cancer * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Pancreatic carcinoma * 1  1/392 (0.26%)  1 1/394 (0.25%)  2
Small cell lung cancer * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Squamous cell carcinoma of skin * 1  7/392 (1.79%)  8 7/394 (1.78%)  23
Tumour pain * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Intestinal adenocarcinoma * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Colorectal cancer metastatic * 1  1/392 (0.26%)  2 0/394 (0.00%)  0
Carcinoid tumour of the small bowel * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Thyroid cancer metastatic * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Lung neoplasm malignant * 1  0/392 (0.00%)  0 1/394 (0.25%)  2
Non-small cell lung cancer metastatic * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Brain neoplasm * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Colorectal cancer * 1  2/392 (0.51%)  3 0/394 (0.00%)  0
Hepatocellular carcinoma * 1  1/392 (0.26%)  2 0/394 (0.00%)  0
Nervous system disorders     
Alexia * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Carotid artery stenosis * 1  0/392 (0.00%)  0 2/394 (0.51%)  2
Cauda equina syndrome * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Cerebrovascular accident * 1  1/392 (0.26%)  1 2/394 (0.51%)  2
Dizziness * 1  2/392 (0.51%)  2 0/394 (0.00%)  0
Haemorrhage intracranial * 1  0/392 (0.00%)  0 1/394 (0.25%)  2
Monoplegia * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Neuralgia * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Paraparesis * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Peripheral sensory neuropathy * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Presyncope * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Radiculopathy * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Sciatica * 1  2/392 (0.51%)  3 0/394 (0.00%)  0
Seizure * 1  1/392 (0.26%)  1 2/394 (0.51%)  2
Spinal cord compression * 1  7/392 (1.79%)  7 9/394 (2.28%)  9
Subarachnoid haemorrhage * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Syncope * 1  2/392 (0.51%)  2 2/394 (0.51%)  2
Transient global amnesia * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Transient ischaemic attack * 1  2/392 (0.51%)  2 2/394 (0.51%)  2
Spinal epidural haematoma * 1  0/392 (0.00%)  0 1/394 (0.25%)  2
Cognitive disorder * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Vascular dementia * 1  1/392 (0.26%)  3 0/394 (0.00%)  0
Ischaemic stroke * 1  2/392 (0.51%)  2 0/394 (0.00%)  0
Parkinson's disease * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Facial neuralgia * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Psychiatric disorders     
Confusional state * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Delirium * 1  2/392 (0.51%)  2 1/394 (0.25%)  1
Depression * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Renal and urinary disorders     
Dysuria * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Haematuria * 1  5/392 (1.28%)  6 4/394 (1.02%)  5
Hydronephrosis * 1  0/392 (0.00%)  0 4/394 (1.02%)  4
Nephrolithiasis * 1  2/392 (0.51%)  3 0/394 (0.00%)  0
Renal colic * 1  0/392 (0.00%)  0 2/394 (0.51%)  3
Urinary bladder haemorrhage * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Urinary incontinence * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Urinary retention * 1  4/392 (1.02%)  5 3/394 (0.76%)  3
Urinary tract obstruction * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Chronic kidney disease * 1  1/392 (0.26%)  3 0/394 (0.00%)  0
Urethral stenosis * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Acute kidney injury * 1  2/392 (0.51%)  2 2/394 (0.51%)  7
Ureterolithiasis * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Reproductive system and breast disorders     
Gynaecomastia * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Pelvic pain * 1  0/392 (0.00%)  0 2/394 (0.51%)  3
Prostatism * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease * 1  2/392 (0.51%)  2 1/394 (0.25%)  2
Dyspnoea * 1  1/392 (0.26%)  1 4/394 (1.02%)  5
Interstitial lung disease * 1  1/392 (0.26%)  3 0/394 (0.00%)  0
Pleural effusion * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Pneumonia aspiration * 1  0/392 (0.00%)  0 2/394 (0.51%)  3
Pneumonitis * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
Pulmonary embolism * 1  6/392 (1.53%)  7 2/394 (0.51%)  2
Respiratory failure * 1  2/392 (0.51%)  3 1/394 (0.25%)  1
Lower respiratory tract inflammation * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Organising pneumonia * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Skin and subcutaneous tissue disorders     
Skin ulcer * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Vascular disorders     
Aortic dissection * 1  1/392 (0.26%)  1 2/394 (0.51%)  3
Aortic stenosis * 1  0/392 (0.00%)  0 1/394 (0.25%)  1
Circulatory collapse * 1  1/392 (0.26%)  1 0/394 (0.00%)  0
Hypertension * 1  1/392 (0.26%)  1 2/394 (0.51%)  3
Hypotension * 1  2/392 (0.51%)  2 1/394 (0.25%)  1
Lymphoedema * 1  0/392 (0.00%)  0 2/394 (0.51%)  2
Peripheral ischaemia * 1  2/392 (0.51%)  5 0/394 (0.00%)  0
Deep vein thrombosis * 1  1/392 (0.26%)  1 1/394 (0.25%)  1
1
Term from vocabulary, MedDRA (22.1)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Radium-223 Dichloride + Abi/Pred Placebo + Abi/Pred
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   369/392 (94.13%)      376/394 (95.43%)    
Blood and lymphatic system disorders     
Anaemia * 1  65/392 (16.58%)  134 61/394 (15.48%)  113
Gastrointestinal disorders     
Abdominal pain * 1  23/392 (5.87%)  24 15/394 (3.81%)  17
Constipation * 1  69/392 (17.60%)  81 79/394 (20.05%)  97
Diarrhoea * 1  69/392 (17.60%)  107 71/394 (18.02%)  102
Dyspepsia * 1  20/392 (5.10%)  23 15/394 (3.81%)  16
Nausea * 1  76/392 (19.39%)  91 67/394 (17.01%)  74
Vomiting * 1  40/392 (10.20%)  48 40/394 (10.15%)  45
General disorders     
Asthenia * 1  37/392 (9.44%)  48 43/394 (10.91%)  60
Fatigue * 1  103/392 (26.28%)  142 95/394 (24.11%)  136
Influenza like illness * 1  12/392 (3.06%)  16 20/394 (5.08%)  24
Oedema peripheral * 1  57/392 (14.54%)  78 64/394 (16.24%)  77
Pyrexia * 1  28/392 (7.14%)  33 34/394 (8.63%)  49
Infections and infestations     
Influenza * 1  22/392 (5.61%)  23 13/394 (3.30%)  21
Nasopharyngitis * 1  31/392 (7.91%)  40 38/394 (9.64%)  53
Upper respiratory tract infection * 1  28/392 (7.14%)  39 33/394 (8.38%)  43
Urinary tract infection * 1  39/392 (9.95%)  54 31/394 (7.87%)  38
Injury, poisoning and procedural complications     
Fall * 1  60/392 (15.31%)  87 50/394 (12.69%)  70
Traumatic fracture * 1  42/392 (10.71%)  72 23/394 (5.84%)  48
Contusion * 1  28/392 (7.14%)  38 31/394 (7.87%)  37
Investigations     
Alanine aminotransferase increased * 1  69/392 (17.60%)  180 61/394 (15.48%)  149
Aspartate aminotransferase increased * 1  61/392 (15.56%)  127 55/394 (13.96%)  104
Weight decreased * 1  20/392 (5.10%)  32 24/394 (6.09%)  34
Metabolism and nutrition disorders     
Hyperglycaemia * 1  12/392 (3.06%)  18 23/394 (5.84%)  50
Hypokalaemia * 1  43/392 (10.97%)  76 43/394 (10.91%)  75
Decreased appetite * 1  65/392 (16.58%)  82 52/394 (13.20%)  54
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  91/392 (23.21%)  133 88/394 (22.34%)  155
Back pain * 1  151/392 (38.52%)  250 138/394 (35.03%)  209
Bone pain * 1  69/392 (17.60%)  96 76/394 (19.29%)  100
Muscle spasms * 1  27/392 (6.89%)  32 30/394 (7.61%)  34
Muscular weakness * 1  25/392 (6.38%)  39 36/394 (9.14%)  50
Musculoskeletal pain * 1  46/392 (11.73%)  55 47/394 (11.93%)  58
Myalgia * 1  25/392 (6.38%)  29 23/394 (5.84%)  26
Neck pain * 1  17/392 (4.34%)  18 24/394 (6.09%)  30
Osteoporosis * 1  27/392 (6.89%)  28 1/394 (0.25%)  1
Osteoporotic fracture * 1  26/392 (6.63%)  75 1/394 (0.25%)  1
Pain in extremity * 1  52/392 (13.27%)  73 58/394 (14.72%)  80
Pathological fracture * 1  48/392 (12.24%)  68 26/394 (6.60%)  40
Musculoskeletal chest pain * 1  28/392 (7.14%)  41 31/394 (7.87%)  39
Spinal pain * 1  30/392 (7.65%)  35 27/394 (6.85%)  34
Nervous system disorders     
Dizziness * 1  45/392 (11.48%)  54 35/394 (8.88%)  41
Headache * 1  30/392 (7.65%)  45 31/394 (7.87%)  39
Psychiatric disorders     
Insomnia * 1  32/392 (8.16%)  35 25/394 (6.35%)  26
Renal and urinary disorders     
Haematuria * 1  31/392 (7.91%)  44 21/394 (5.33%)  28
Reproductive system and breast disorders     
Pelvic pain * 1  12/392 (3.06%)  16 21/394 (5.33%)  31
Respiratory, thoracic and mediastinal disorders     
Cough * 1  36/392 (9.18%)  42 41/394 (10.41%)  50
Dyspnoea * 1  20/392 (5.10%)  28 31/394 (7.87%)  35
Vascular disorders     
Hypertension * 1  61/392 (15.56%)  164 80/394 (20.30%)  213
Hot flush * 1  23/392 (5.87%)  25 51/394 (12.94%)  53
1
Term from vocabulary, MedDRA (22.1)
*
Indicates events were collected by non-systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: Bayer
Phone: 1-888-8422937
EMail: clinical-trials-contact@bayer.com
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02043678    
Other Study ID Numbers: 15396
2013-003438-33 ( EudraCT Number )
First Submitted: January 21, 2014
First Posted: January 23, 2014
Results First Submitted: February 12, 2019
Results First Posted: March 5, 2019
Last Update Posted: May 11, 2021