ERA 223: 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
Sponsor
Bayer (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02043678
Collaborator
Janssen Research & Development, LLC (Industry)
806
165
2
119.6
4.9
0
Study Details
Study Description
Brief Summary
To determine if the addition of radium-223 dichloride to standard treatment is able to prolong life and to delay events specific for prostate cancer which has spread to the bone, such as painful fractures or bone pain which needs to be treated with an X-ray machine.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This study is a phase III multinational, multicenter,randomized, double blind, placebo controlled, study with a randomization allocation ratio of 1:1 (radium-223 dichloride plus abiraterone acetate plus prednisone/prednisolone: placebo plus abiraterone acetate plus prednisone/prednisolone). Until the final overall survival (OS) analysis, the study period consisted of screening / randomization, treatment, active follow-up with clinic visits, active follow-up without clinic visits, and longterm follow-up phases. Up until this point, subjects received study treatment (radium-223 dichloride or placebo in addition to abiraterone acetate plus prednisone / prednisolone for the first 6 cycles followed by abiraterone acetate plus prednisone / prednisolone thereafter) until an on-study SSE occurred (or other withdrawal criteria were met). After the final OS analysis (after implementation of Amendment 7), in order to reduce the burden to study subjects, evaluation of efficacy and exploratory endpoints will be discontinued, except for symptomatic skeletal event (SSE) and OS. Subjects who are discontinued from study treatment will initiate the long-term follow-up period; therefore, active follow-up periods will no longer be applicable. Subjects who are in active follow-up at the time of Amendment 7 is implemented should have the end of active follow-up completed (protocol driven decision) and should be directly transitioned into the extended safety follow-up study. Long term follow-up will continue until the subject dies, is lost to follow-up, withdraws informed consent, actively objects to collection of further data, or is transitioned to the extended safety follow-up study. Subjects will be followed for safety for up to 7 years, which eventually will be completed in the extended safety follow-up study.
Study Design
Study Type:
Interventional
Actual Enrollment
:
806 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase III Randomized, Double-blind, Placebo-controlled Trial of Radium-223 Dichloride in Combination With Abiraterone Acetate and Prednisone/Prednisolone in the Treatment of Asymptomatic or Mildly Symptomatic Chemotherapy-naïve Subjects With Bone Predominant Metastatic Castration-resistant Prostate Cancer(CRPC)
Actual Study Start Date
:
Mar 30, 2014
Actual Primary Completion Date
:
Feb 15, 2018
Anticipated Study Completion Date
:
Mar 18, 2024
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Radium-223 dichloride + Abi/Pred 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) |
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of NIST update) body weight, intravenous injection (IV-slow bolus), every 4 weeks for 6 cycles
Drug: Abiraterone
1000 mg once daily, oral, with best supportive care
Drug: Prednisone/Prednisolone
5 mg twice daily, oral, with best supportive care
|
| Placebo Comparator: Placebo + Abi/Pred 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) |
Drug: Matching placebo (normal saline)
Intravenous injection ( IV-slow bolus), every 4 weeks for 6 cycles
Drug: Abiraterone
1000 mg once daily, oral, with best supportive care
Drug: Prednisone/Prednisolone
5 mg twice daily, oral, with best supportive care
|
Outcome Measures
Primary Outcome Measures
- Symptomatic Skeletal Event Free Survival (SSE-FS) [From randomization until first onset of on-study symptomatic skeletal event (SSE) or death, up to 47 months]
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.
Secondary Outcome Measures
- Overall Survival (OS) [From randomization until death from any cause, up to 67 months]
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.
- Radiological Progression Free Survival (rPFS) [From randomization until the date of confirmed radiological progression or death, up to 47 months]
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 to Pain Progression [From randomization until the date of pain progression based on pain score, up to 47 months]
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 to Cytotoxic Chemotherapy [From randomization until the date of first cytotoxic chemotherapy, up to 47 months]
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 to Opiate Use for Cancer Pain [From randomization until the date of opiate use, up to 47 months]
Time to opiate use for cancer pain was defined as the interval from the date of randomization to the date of opiate use.
- Number of Participants With Treatment-emergent Adverse Events [From start of study treatment until the end of the treatment period, up to 65 months]
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.
- Number of Subjects With Radium-223/Placebo-related Treatment-emergent Adverse Events Per Maximum Intensity [From start of study treatment until the end of the treatment period, up to 65 months]
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.
- Number of Participants With Any Treatment-emergent Additional Primary Malignancies [From start of study treatment until 4 weeks after last study treatment, up to 65 months]
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.
- Number of Participants With Treatment-emergent Bone Fractures [From start of study treatment until 4 weeks after last study treatment, up to 65 months]
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.
- Number of Participants With Post-treatment Adverse Events [After the treatment period, up to 46 months]
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.
- Number of Participants With Any Study Drug-related Post-treatment Adverse Events Per Maximum Intensity [After the treatment period, up to 46 months]
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.
- Number of Participants With Post-treatment Chemotherapy-related Blood and Lymphatic System Disorders [After the treatment period, up to 46 months]
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.
- Number of Participants With Post-treatment Bone Fractures [After the treatment period, up to 46 months]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histologically confirmed adenocarcinoma of the prostate
-
Male subjects of age ≥ 18 years
-
Prostate cancer progression documented by prostate specific antigen (PSA) according to the Prostate Cancer Working Group 2 (PCWG2) criteria or radiological progression according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
-
Two or more bone metastases on bone scan within 4 weeks prior to randomization with no lung, liver, other visceral and/or brain metastasis
-
Asymptomatic or mildly symptomatic prostate cancer
-
Subjects who received combined androgen blockade with an anti-androgen must have shown PSA progression after discontinuing the anti-androgen prior to enrollment
-
Maintenance of medical castration or surgical castration with testosterone less than 50 ng/dL (1.7nmol/L)
-
Eastern Cooperative Oncology Group performance status (ECOG PS) score 0 or 1
Exclusion Criteria:
-
Prior cytotoxic chemotherapy for the treatment of CRPC, including taxanes, mitoxantrone and estramustine
-
Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone/prednisolone twice daily
-
Pathological finding consistent with small cell carcinoma of the prostate
-
History of visceral metastasis, or presence of visceral metastasis detected by screening imaging examinations
-
History of or known brain metastasis
-
Malignant lymphadenopathy exceeding 3 cm in short-axis diameter
-
Blood transfusion or erythropoietin stimulating agents prior 4 weeks of screening and during the whole screening period before randomization
-
Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Subjects with history of spinal cord compression should have completely recovered
-
Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or anytime during the 4- week period prior to randomization.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Anchorage | Alaska | United States | 99503 | |
| 2 | Tucson | Arizona | United States | 85704 | |
| 3 | Tucson | Arizona | United States | 85718 | |
| 4 | Oceanside | California | United States | 92056 | |
| 5 | Denver | Colorado | United States | 80211 | |
| 6 | Washington | District of Columbia | United States | 20007-2113 | |
| 7 | Fort Myers | Florida | United States | 33901 | |
| 8 | Atlanta | Georgia | United States | 30322 | |
| 9 | Jeffersonville | Indiana | United States | 47130 | |
| 10 | New Orleans | Louisiana | United States | 70112 | |
| 11 | Baltimore | Maryland | United States | 21201 | |
| 12 | Rockville | Maryland | United States | 20850 | |
| 13 | Towson | Maryland | United States | 21204 | |
| 14 | Boston | Massachusetts | United States | 02114-2696 | |
| 15 | Burlington | Massachusetts | United States | 01805 | |
| 16 | Detroit | Michigan | United States | 48202 | |
| 17 | Traverse City | Michigan | United States | 49684 | |
| 18 | Saint Louis | Missouri | United States | 63110 | |
| 19 | Omaha | Nebraska | United States | 68130 | |
| 20 | Las Vegas | Nevada | United States | 89169 | |
| 21 | Hackensack | New Jersey | United States | 07601 | |
| 22 | Poughkeepsie | New York | United States | 12601 | |
| 23 | Syracuse | New York | United States | 13210 | |
| 24 | Bala-Cynwyd | Pennsylvania | United States | 19004 | |
| 25 | Pittsburgh | Pennsylvania | United States | 15215 | |
| 26 | Pittsburgh | Pennsylvania | United States | 15240 | |
| 27 | Norfolk | Virginia | United States | 23502 | |
| 28 | Seattle | Washington | United States | 98109-1023 | |
| 29 | Spokane | Washington | United States | 99208-1129 | |
| 30 | Wheeling | West Virginia | United States | 26003 | |
| 31 | St Leonards | New South Wales | Australia | 2065 | |
| 32 | Adelaide | South Australia | Australia | 5000 | |
| 33 | East Bentleigh | Victoria | Australia | 3165 | |
| 34 | Heidelberg | Victoria | Australia | 3084 | |
| 35 | Melbourne | Victoria | Australia | 3065 | |
| 36 | Darlinghurst | Australia | 2010 | ||
| 37 | East Melbourne | Australia | 3002 | ||
| 38 | Randwick | Australia | 2031 | ||
| 39 | Anderlecht | Belgium | 1070 | ||
| 40 | Bruxelles - Brussel | Belgium | 1200 | ||
| 41 | Edegem | Belgium | 2650 | ||
| 42 | Gent | Belgium | 9000 | ||
| 43 | Belo Horizonte | Minas Gerais | Brazil | 30110-090 | |
| 44 | Porto Alegre | Rio Grande Do Sul | Brazil | 90050-170 | |
| 45 | Barretos | Sao Paulo | Brazil | 14784-400 | |
| 46 | São Paulo | Sao Paulo | Brazil | 01246-000 | |
| 47 | Sao Paulo | Brazil | 01308-050 | ||
| 48 | Calgary | Alberta | Canada | T2N 4N2 | |
| 49 | Vancouver | British Columbia | Canada | V5Z 4E6 | |
| 50 | Winnipeg | Manitoba | Canada | R3A 1R9 | |
| 51 | Hamilton | Ontario | Canada | L8V 5C2 | |
| 52 | Ottawa | Ontario | Canada | K1H 8L6 | |
| 53 | Toronto | Ontario | Canada | M4N 3M5 | |
| 54 | Montreal | Quebec | Canada | H2L 4M1 | |
| 55 | Quebec | Canada | G1R 2J6 | ||
| 56 | Helsinki | Finland | 00290 | ||
| 57 | Kuopio | Finland | 70210 | ||
| 58 | Seinäjoki | Finland | 60220 | ||
| 59 | Tampere | Finland | 33521 | ||
| 60 | Besancon | France | 25030 | ||
| 61 | Bordeaux Cedex | France | 33076 | ||
| 62 | Paris | France | 75005 | ||
| 63 | Paris | France | 75010 | ||
| 64 | POITIERS cedex | France | 86021 | ||
| 65 | Saint Herblain | France | 44805 | ||
| 66 | Toulouse Cedex 9 | France | 31059 | ||
| 67 | Ulm | Baden-Württemberg | Germany | 89075 | |
| 68 | München | Bayern | Germany | 81675 | |
| 69 | Marburg | Hessen | Germany | 35043 | |
| 70 | Münster | Nordrhein-Westfalen | Germany | 48149 | |
| 71 | Dresden | Sachsen | Germany | 01307 | |
| 72 | Jena | Thüringen | Germany | 07747 | |
| 73 | Berlin | Germany | 12203 | ||
| 74 | Afula | Israel | 1834111 | ||
| 75 | Beer Sheva | Israel | 8410101 | ||
| 76 | Haifa | Israel | 3109601 | ||
| 77 | Jerusalem | Israel | 9112001 | ||
| 78 | Kfar Saba | Israel | 4428164 | ||
| 79 | Petach Tikva | Israel | 4941492 | ||
| 80 | Ramat Gan | Israel | 5262000 | ||
| 81 | Tel Aviv | Israel | 6423906 | ||
| 82 | Zrifin | Israel | 7030000 | ||
| 83 | Modena | Emilia-Romagna | Italy | 41124 | |
| 84 | Roma | Lazio | Italy | 00152 | |
| 85 | Roma | Lazio | Italy | 00189 | |
| 86 | Genova | Liguria | Italy | 16128 | |
| 87 | Milano | Lombardia | Italy | 20133 | |
| 88 | Milano | Lombardia | Italy | 20141 | |
| 89 | Cagliari | Sardegna | Italy | 09125 | |
| 90 | Arezzo | Toscana | Italy | 52100 | |
| 91 | Trento | Trentino-Alto Adige | Italy | 38100 | |
| 92 | Nagoya | Aichi | Japan | 466-8560 | |
| 93 | Hirosaki | Aomori | Japan | 036-8563 | |
| 94 | Kashiwa | Chiba | Japan | 277-8577 | |
| 95 | Matsuyama | Ehime | Japan | 791-0280 | |
| 96 | Sapporo | Hokkaido | Japan | 003-0804 | |
| 97 | Kobe | Hyogo | Japan | 650-0047 | |
| 98 | Tsukuba | Ibaraki | Japan | 305-8576 | |
| 99 | Kanazawa | Ishikawa | Japan | 920-8641 | |
| 100 | Kita | Kagawa | Japan | 761-0793 | |
| 101 | Yokohama | Kanagawa | Japan | 236-0004 | |
| 102 | Yokohama | Kanagawa | Japan | 241-8515 | |
| 103 | Sendai | Miyagi | Japan | 980-8574 | |
| 104 | Matsumoto | Nagano | Japan | 390-8621 | |
| 105 | Kurashiki | Okayama | Japan | 701-0192 | |
| 106 | Osakasayama | Osaka | Japan | 589-8511 | |
| 107 | Hamamatsu | Shizuoka | Japan | 431-3192 | |
| 108 | Bunkyo-ku | Tokyo | Japan | 113-8431 | |
| 109 | Bunkyo-ku | Tokyo | Japan | 113-8603 | |
| 110 | Koto-ku | Tokyo | Japan | 135-8550 | |
| 111 | Shinjuku-ku | Tokyo | Japan | 160-8582 | |
| 112 | Ube | Yamaguchi | Japan | 755-8505 | |
| 113 | Chiba | Japan | 260-8677 | ||
| 114 | Chiba | Japan | 260-8717 | ||
| 115 | Fukuoka | Japan | 811-1395 | ||
| 116 | Fukuoka | Japan | 812-8582 | ||
| 117 | Kumamoto | Japan | 860-0008 | ||
| 118 | Miyazaki | Japan | 889-1692 | ||
| 119 | Nagasaki | Japan | 852-8501 | ||
| 120 | Okayama | Japan | 700-8558 | ||
| 121 | Amsterdam | Netherlands | 1105 AZ | ||
| 122 | Nijmegen | Netherlands | 6525 GA | ||
| 123 | Zwolle | Netherlands | 8025 AB | ||
| 124 | Bodø | Norway | 8092 | ||
| 125 | Lørenskog | Norway | 1478 | ||
| 126 | Oslo | Norway | 0450 | ||
| 127 | Gdansk | Poland | 80-952 | ||
| 128 | Gdynia | Poland | 81-519 | ||
| 129 | Gliwice | Poland | 44-101 | ||
| 130 | Poznan | Poland | 61-485 | ||
| 131 | Moscow | Russian Federation | 115478 | ||
| 132 | Obninsk | Russian Federation | 249036 | ||
| 133 | Singapore | Singapore | 119074 | ||
| 134 | Singapore | Singapore | 169608 | ||
| 135 | Singapore | Singapore | 169610 | ||
| 136 | Singapore | Singapore | 258499 | ||
| 137 | Oviedo | Asturias | Spain | 33006 | |
| 138 | Badalona | Barcelona | Spain | 08916 | |
| 139 | Hospitalet de Llobregat | Barcelona | Spain | 08907 | |
| 140 | Barcelona | Spain | 08035 | ||
| 141 | Barcelona | Spain | 08036 | ||
| 142 | Madrid | Spain | 28007 | ||
| 143 | Madrid | Spain | 28033 | ||
| 144 | Madrid | Spain | 28034 | ||
| 145 | Madrid | Spain | 28046 | ||
| 146 | Madrid | Spain | 28050 | ||
| 147 | Málaga | Spain | 29010 | ||
| 148 | Pamplona | Spain | 31008 | ||
| 149 | Sevilla | Spain | 41009 | ||
| 150 | Linköping | Sweden | 58185 | ||
| 151 | Stockholm | Sweden | 171 76 | ||
| 152 | Sundsvall | Sweden | 851 86 | ||
| 153 | Umeå | Sweden | 901 85 | ||
| 154 | Växjö | Sweden | 351 85 | ||
| 155 | Edinburgh | Lothian | United Kingdom | EH4 2XU | |
| 156 | Bebington | Merseyside | United Kingdom | CH63 4JY | |
| 157 | Northwood | Middlesex | United Kingdom | HA6 2VR | |
| 158 | Guildford | Surrey | United Kingdom | GU2 7XX | |
| 159 | Sutton | Surrey | United Kingdom | SM2 5PT | |
| 160 | Newcastle Upon Tyne | Tyne And Wear | United Kingdom | NE4 6BE | |
| 161 | Coventry | Warwickshire | United Kingdom | CV2 2DX | |
| 162 | Belfast | United Kingdom | BT9 7AB | ||
| 163 | Leeds | United Kingdom | LS9 7TF | ||
| 164 | London | United Kingdom | NW3 2QG | ||
| 165 | Romford | United Kingdom | RM7 0AG |
Sponsors and Collaborators
- Bayer
- Janssen Research & Development, LLC
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
More Information
Additional Information:
- Click here to find results for studies related to Bayer products.
- Click here to find information about studies related to Bayer Healthcare products conducted in Europe
Publications
None provided.Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT02043678
Other Study ID Numbers:
- 15396
- 2013-003438-33
First Posted:
Jan 23, 2014
Last Update Posted:
Aug 17, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Bayer
Additional relevant MeSH terms:
Study Results
Participant Flow
| 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 Detail | 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 |
|---|---|---|
| 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 | 0 | 0 |
| NOT COMPLETED | 401 | 405 |
Baseline Characteristics
| Arm/Group Title | Radium-223 Dichloride + Abi/Pred | Placebo + Abi/Pred | Total |
|---|---|---|---|
| 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 Participants | 401 | 405 | 806 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
70.9
(8.5)
|
71.4
(8.4)
|
71.1
(8.5)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
401
100%
|
405
100%
|
806
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
17
4.2%
|
23
5.7%
|
40
5%
|
| Not Hispanic or Latino |
361
90%
|
355
87.7%
|
716
88.8%
|
| Unknown or Not Reported |
23
5.7%
|
27
6.7%
|
50
6.2%
|
| Race (NIH/OMB) (Count of 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%
|
| Black or African American |
10
2.5%
|
16
4%
|
26
3.2%
|
| White |
285
71.1%
|
284
70.1%
|
569
70.6%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
26
6.5%
|
26
6.4%
|
52
6.5%
|
| Weight (Kilograms (kg)) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Kilograms (kg)] |
82.19
(16.75)
|
82.40
(16.01)
|
82.30
(16.37)
|
| Stage of prostate cancer at diagnosis (Tumor Node Metastasis [TNM] Classification) (Count of 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%
|
| Cancer pain assessment by Brief Pain Inventory-Short Form (BPI-SF) (Count of 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%
|
355
44%
|
| Gleason score at diagnosis (Count of Participants) | |||
| Missing |
15
3.7%
|
18
4.4%
|
33
4.1%
|
| Less than (<) 8 |
140
34.9%
|
154
38%
|
294
36.5%
|
| Greater than or equal to (>=) 8 |
246
61.3%
|
233
57.5%
|
479
59.4%
|
| Prostate-specific antigen (Micrograms per liter (ug/L)) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Micrograms per liter (ug/L)] |
92.39
(191.62)
|
92.33
(328.00)
|
92.36
(268.85)
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of 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%
|
| Extent of Disease (Count of Participants) | |||
| Normal or abnormal because of benign bone disease |
2
0.5%
|
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%
|
Outcome Measures
| Title | Symptomatic Skeletal Event Free Survival (SSE-FS) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) analysis set (included all randomized participants) |
| Arm/Group Title | Radium-223 Dichloride + Abi/Pred | Placebo + Abi/Pred |
|---|---|---|
| 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). |
| Measure Participants | 401 | 405 |
| Median (95% Confidence Interval) [Months] |
22.3
|
26.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Radium-223 Dichloride + Abi/Pred, Placebo + Abi/Pred |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2636 |
| Comments | ||
| Method | Cox Proportional Hazards Model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.122 | |
| Confidence Interval |
(2-Sided) 95% 0.917 to 1.374 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (OS) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT analysis set (included all randomized participants) |
| Arm/Group Title | Radium-223 Dichloride + Abi/Pred | Placebo + Abi/Pred |
|---|---|---|
| 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). |
| Measure Participants | 401 | 405 |
| Median (95% Confidence Interval) [Months] |
30.1
|
34.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Radium-223 Dichloride + Abi/Pred, Placebo + Abi/Pred |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1194 |
| Comments | ||
| Method | Cox Proportional Hazards model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.151 | |
| Confidence Interval |
(2-Sided) 95% 0.964 to 1.374 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Radiological Progression Free Survival (rPFS) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT analysis set (included all randomized participants) |
| Arm/Group Title | Radium-223 Dichloride + Abi/Pred | Placebo + Abi/Pred |
|---|---|---|
| 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). |
| Measure Participants | 401 | 405 |
| Median (95% Confidence Interval) [Months] |
11.2
|
12.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Radium-223 Dichloride + Abi/Pred, Placebo + Abi/Pred |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1283 |
| Comments | ||
| Method | Cox Proportional Hazards Model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.152 | |
| Confidence Interval |
(2-Sided) 95% 0.960 to 1.383 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Pain Progression |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT analysis set (included all randomized participants) |
| Arm/Group Title | Radium-223 Dichloride + Abi/Pred | Placebo + Abi/Pred |
|---|---|---|
| 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). |
| Measure Participants | 401 | 405 |
| Median (95% Confidence Interval) [Months] |
14.4
|
18.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Radium-223 Dichloride + Abi/Pred, Placebo + Abi/Pred |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1669 |
| Comments | ||
| Method | Cox Proportional Hazards Model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.145 | |
| Confidence Interval |
(2-Sided) 95% 0.945 to 1.389 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Cytotoxic Chemotherapy |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT analysis set (included all randomized participants) |
| Arm/Group Title | Radium-223 Dichloride + Abi/Pred | Placebo + Abi/Pred |
|---|---|---|
| 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). |
| Measure Participants | 401 | 405 |
| Median (95% Confidence Interval) [Months] |
29.5
|
28.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Radium-223 Dichloride + Abi/Pred, Placebo + Abi/Pred |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7871 |
| Comments | ||
| Method | Cox Proportional Hazards Model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.033 | |
| Confidence Interval |
(2-Sided) 95% 0.816 to 1.308 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Opiate Use for Cancer Pain |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 398 | 392 |
| Median (95% Confidence Interval) [Months] |
19.0
|
22.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Radium-223 Dichloride + Abi/Pred, Placebo + Abi/Pred |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2467 |
| Comments | ||
| Method | Cox Proportional Hazards Model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.126 | |
| Confidence Interval |
(2-Sided) 95% 0.921 to 1.378 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Treatment-emergent Adverse Events |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 392 | 394 |
| Any TEAE |
382
95.3%
|
387
95.6%
|
| Any drug-related TEAE |
265
66.1%
|
271
66.9%
|
| Radium-223/Placebo-related TEAE |
92
22.9%
|
92
22.7%
|
| Any serious TEAE |
175
43.6%
|
172
42.5%
|
| Any drug-related serious TEAE |
32
8%
|
29
7.2%
|
| Radium-223/Placebo-related serious TEAE |
11
2.7%
|
7
1.7%
|
| Title | Number of Subjects With Radium-223/Placebo-related Treatment-emergent Adverse Events Per Maximum Intensity |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 392 | 394 |
| TEAE - Grade 1 |
44
11%
|
53
13.1%
|
| TEAE - Grade 2 |
28
7%
|
24
5.9%
|
| TEAE - Grade 3 |
19
4.7%
|
13
3.2%
|
| TEAE - Grade 4 |
1
0.2%
|
2
0.5%
|
| Serious TEAE - Grade 2 |
3
0.7%
|
0
0%
|
| Serious TEAE - Grade 3 |
8
2%
|
5
1.2%
|
| Serious TEAE - Grade 4 |
0
0%
|
2
0.5%
|
| Title | Number of Participants With Any Treatment-emergent Additional Primary Malignancies |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 392 | 394 |
| Count of Participants [Participants] |
26
6.5%
|
25
6.2%
|
| Title | Number of Participants With Treatment-emergent Bone Fractures |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 392 | 394 |
| Count of Participants [Participants] |
107
26.7%
|
49
12.1%
|
| Title | Number of Participants With Post-treatment Adverse Events |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 392 | 394 |
| Any events |
138
34.4%
|
133
32.8%
|
| Any drug-related events |
18
4.5%
|
9
2.2%
|
| Any chemotherapy-related events |
31
7.7%
|
34
8.4%
|
| Any additional primary malignancies |
6
1.5%
|
7
1.7%
|
| Title | Number of Participants With Any Study Drug-related Post-treatment Adverse Events Per Maximum Intensity |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 392 | 394 |
| Grade 1 |
3
0.7%
|
3
0.7%
|
| Grade 2 |
9
2.2%
|
3
0.7%
|
| Grade 3 |
5
1.2%
|
3
0.7%
|
| Grade 4 |
1
0.2%
|
0
0%
|
| Title | Number of Participants With Post-treatment Chemotherapy-related Blood and Lymphatic System Disorders |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 392 | 394 |
| Anaemia |
5
1.2%
|
4
1%
|
| Bone marrow failure |
1
0.2%
|
0
0%
|
| Febrile neutropenia |
5
1.2%
|
8
2%
|
| Leukopenia |
1
0.2%
|
0
0%
|
| Neutropenia |
8
2%
|
3
0.7%
|
| Pancytopenia |
0
0%
|
1
0.2%
|
| Thrombocytopenia |
2
0.5%
|
2
0.5%
|
| Title | Number of Participants With Post-treatment Bone Fractures |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 392 | 394 |
| Lumbar vertebral fracture |
0
0%
|
1
0.2%
|
| Rib fracture |
0
0%
|
1
0.2%
|
| Spinal compression fracture |
0
0%
|
1
0.2%
|
| Thoracic vertebral fracture |
0
0%
|
1
0.2%
|
| Traumatic fracture |
6
1.5%
|
2
0.5%
|
| Osteoporotic fracture |
6
1.5%
|
0
0%
|
| Pathological fracture |
12
3%
|
13
3.2%
|
Adverse Events
| 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 | ||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 254/392 (64.8%) | 242/394 (61.4%) | ||
Serious Adverse Events |
||||
| Radium-223 Dichloride + Abi/Pred | Placebo + Abi/Pred | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 190/392 (48.5%) | 185/394 (47%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 9/392 (2.3%) | 19 | 4/394 (1%) | 5 |
| Disseminated intravascular coagulation | 0/392 (0%) | 0 | 1/394 (0.3%) | 2 |
| Febrile neutropenia | 3/392 (0.8%) | 3 | 6/394 (1.5%) | 6 |
| Leukopenia | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Lymphopenia | 1/392 (0.3%) | 6 | 0/394 (0%) | 0 |
| Neutropenia | 2/392 (0.5%) | 2 | 1/394 (0.3%) | 1 |
| Pancytopenia | 0/392 (0%) | 0 | 2/394 (0.5%) | 2 |
| Thrombocytopenia | 3/392 (0.8%) | 9 | 0/394 (0%) | 0 |
| Bone marrow failure | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Cardiac disorders | ||||
| Acute myocardial infarction | 5/392 (1.3%) | 6 | 4/394 (1%) | 4 |
| Aortic valve incompetence | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Aortic valve stenosis | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Arrhythmia | 0/392 (0%) | 0 | 1/394 (0.3%) | 2 |
| Atrial fibrillation | 4/392 (1%) | 5 | 8/394 (2%) | 8 |
| Atrial flutter | 1/392 (0.3%) | 2 | 1/394 (0.3%) | 1 |
| Atrioventricular block complete | 2/392 (0.5%) | 3 | 0/394 (0%) | 0 |
| Cardiac arrest | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Cardiac failure | 1/392 (0.3%) | 2 | 3/394 (0.8%) | 6 |
| Cardiac failure congestive | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Cardio-respiratory arrest | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Coronary artery stenosis | 0/392 (0%) | 0 | 2/394 (0.5%) | 2 |
| Coronary ostial stenosis | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Myocardial infarction | 3/392 (0.8%) | 4 | 1/394 (0.3%) | 1 |
| Sinus bradycardia | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Ventricular fibrillation | 1/392 (0.3%) | 2 | 1/394 (0.3%) | 2 |
| Ventricular tachycardia | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Acute coronary syndrome | 2/392 (0.5%) | 2 | 0/394 (0%) | 0 |
| Cardiac disorder | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||
| Inborn error of metabolism | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Ear and labyrinth disorders | ||||
| Vertigo | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Endocrine disorders | ||||
| Primary adrenal insufficiency | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Eye disorders | ||||
| Cataract | 1/392 (0.3%) | 1 | 2/394 (0.5%) | 2 |
| Retinal artery occlusion | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Abdominal pain lower | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Constipation | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Diarrhoea | 3/392 (0.8%) | 3 | 5/394 (1.3%) | 5 |
| Diverticulum intestinal haemorrhagic | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Duodenal ulcer | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Dysphagia | 2/392 (0.5%) | 2 | 0/394 (0%) | 0 |
| Enterocolitis | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Gastric haemorrhage | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Gastric ulcer | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Gastrointestinal disorder | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Gastrointestinal haemorrhage | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Ileus | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Incarcerated inguinal hernia | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Inguinal hernia | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Large intestine perforation | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Nausea | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Oesophageal achalasia | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Oesophageal ulcer | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Rectal haemorrhage | 0/392 (0%) | 0 | 2/394 (0.5%) | 2 |
| Small intestinal obstruction | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Small intestinal perforation | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Vomiting | 3/392 (0.8%) | 3 | 2/394 (0.5%) | 2 |
| Lower gastrointestinal haemorrhage | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Large intestine polyp | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Anal prolapse | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| General disorders | ||||
| Asthenia | 1/392 (0.3%) | 2 | 4/394 (1%) | 6 |
| Death | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Fatigue | 2/392 (0.5%) | 2 | 2/394 (0.5%) | 2 |
| Influenza like illness | 0/392 (0%) | 0 | 1/394 (0.3%) | 2 |
| Malaise | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Oedema peripheral | 2/392 (0.5%) | 2 | 1/394 (0.3%) | 1 |
| Pain | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Pyrexia | 5/392 (1.3%) | 5 | 4/394 (1%) | 4 |
| Sudden death | 0/392 (0%) | 0 | 2/394 (0.5%) | 2 |
| Peripheral swelling | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| General physical health deterioration | 10/392 (2.6%) | 14 | 13/394 (3.3%) | 19 |
| Physical deconditioning | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Non-cardiac chest pain | 2/392 (0.5%) | 2 | 1/394 (0.3%) | 1 |
| Multiple organ dysfunction syndrome | 2/392 (0.5%) | 2 | 0/394 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Cholecystitis | 0/392 (0%) | 0 | 1/394 (0.3%) | 2 |
| Cholecystitis acute | 1/392 (0.3%) | 1 | 2/394 (0.5%) | 2 |
| Hepatic function abnormal | 0/392 (0%) | 0 | 1/394 (0.3%) | 2 |
| Bile duct obstruction | 1/392 (0.3%) | 2 | 0/394 (0%) | 0 |
| Hepatobiliary disease | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Infections and infestations | ||||
| Acute sinusitis | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Appendicitis | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Bacteraemia | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Bronchitis | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Cellulitis | 3/392 (0.8%) | 3 | 2/394 (0.5%) | 2 |
| Clostridium difficile colitis | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Diverticulitis | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Encephalitis | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Erysipelas | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Gastroenteritis | 3/392 (0.8%) | 3 | 2/394 (0.5%) | 2 |
| Gastroenteritis clostridial | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Gastrointestinal infection | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Infection | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Influenza | 1/392 (0.3%) | 1 | 2/394 (0.5%) | 2 |
| Lower respiratory tract infection | 2/392 (0.5%) | 2 | 1/394 (0.3%) | 1 |
| Lyme disease | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Osteomyelitis | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Pneumonia | 12/392 (3.1%) | 15 | 16/394 (4.1%) | 20 |
| Pulmonary tuberculosis | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Sepsis | 2/392 (0.5%) | 4 | 4/394 (1%) | 7 |
| Septic shock | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Sinusitis | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Skin infection | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Upper respiratory tract infection | 0/392 (0%) | 0 | 5/394 (1.3%) | 6 |
| Urinary tract infection | 18/392 (4.6%) | 21 | 10/394 (2.5%) | 12 |
| Viral upper respiratory tract infection | 0/392 (0%) | 0 | 2/394 (0.5%) | 3 |
| Wound infection | 1/392 (0.3%) | 3 | 0/394 (0%) | 0 |
| Urosepsis | 1/392 (0.3%) | 1 | 6/394 (1.5%) | 12 |
| Tooth infection | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Acute endocarditis | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Neutropenic sepsis | 2/392 (0.5%) | 2 | 0/394 (0%) | 0 |
| Groin infection | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Pulmonary sepsis | 2/392 (0.5%) | 4 | 1/394 (0.3%) | 1 |
| Arthritis bacterial | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Clostridium difficile infection | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Infective exacerbation of chronic obstructive airways disease | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Staphylococcal infection | 0/392 (0%) | 0 | 1/394 (0.3%) | 2 |
| Pneumonia bacterial | 0/392 (0%) | 0 | 1/394 (0.3%) | 2 |
| Arthritis infective | 1/392 (0.3%) | 2 | 0/394 (0%) | 0 |
| Respiratory tract infection | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Encephalitis fungal | 1/392 (0.3%) | 2 | 0/394 (0%) | 0 |
| Gastroenteritis norovirus | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Large intestine infection | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Alcohol poisoning | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Fall | 0/392 (0%) | 0 | 3/394 (0.8%) | 3 |
| Femoral neck fracture | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Femur fracture | 0/392 (0%) | 0 | 2/394 (0.5%) | 2 |
| Humerus fracture | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Joint dislocation | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Pneumothorax traumatic | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Radius fracture | 0/392 (0%) | 0 | 1/394 (0.3%) | 2 |
| Soft tissue injury | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Spinal compression fracture | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Subdural haematoma | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Ulna fracture | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Traumatic fracture | 13/392 (3.3%) | 19 | 5/394 (1.3%) | 5 |
| Lumbar vertebral fracture | 1/392 (0.3%) | 2 | 0/394 (0%) | 0 |
| Brain contusion | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Pseudophakic bullous keratopathy | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase increased | 2/392 (0.5%) | 6 | 1/394 (0.3%) | 1 |
| Aspartate aminotransferase increased | 2/392 (0.5%) | 5 | 1/394 (0.3%) | 1 |
| Blood bilirubin increased | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Blood lactate dehydrogenase increased | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Platelet count decreased | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 3 |
| Weight decreased | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Influenza A virus test positive | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 4/392 (1%) | 4 | 1/394 (0.3%) | 1 |
| Diabetes mellitus | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Hypercalcaemia | 0/392 (0%) | 0 | 1/394 (0.3%) | 3 |
| Hyperglycaemia | 1/392 (0.3%) | 1 | 2/394 (0.5%) | 3 |
| Hypokalaemia | 2/392 (0.5%) | 3 | 1/394 (0.3%) | 3 |
| Hyponatraemia | 1/392 (0.3%) | 2 | 2/394 (0.5%) | 11 |
| Iron deficiency | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Decreased appetite | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Hypophagia | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 3/392 (0.8%) | 3 | 2/394 (0.5%) | 2 |
| Back pain | 8/392 (2%) | 10 | 11/394 (2.8%) | 12 |
| Bone pain | 7/392 (1.8%) | 8 | 5/394 (1.3%) | 8 |
| Bursitis | 0/392 (0%) | 0 | 1/394 (0.3%) | 2 |
| Lumbar spinal stenosis | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Muscular weakness | 3/392 (0.8%) | 4 | 2/394 (0.5%) | 3 |
| Musculoskeletal pain | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 2 |
| Neck pain | 1/392 (0.3%) | 1 | 2/394 (0.5%) | 2 |
| Osteoarthritis | 1/392 (0.3%) | 1 | 2/394 (0.5%) | 2 |
| Osteonecrosis | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Osteoporosis | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Osteoporotic fracture | 9/392 (2.3%) | 14 | 1/394 (0.3%) | 3 |
| Pain in extremity | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Pathological fracture | 8/392 (2%) | 13 | 4/394 (1%) | 4 |
| Rhabdomyolysis | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Spinal osteoarthritis | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Mobility decreased | 1/392 (0.3%) | 2 | 0/394 (0%) | 0 |
| Intervertebral disc protrusion | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Osteonecrosis of jaw | 3/392 (0.8%) | 3 | 1/394 (0.3%) | 1 |
| Spinal pain | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Adenocarcinoma gastric | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Adenocarcinoma of colon | 1/392 (0.3%) | 3 | 1/394 (0.3%) | 1 |
| Anaplastic thyroid cancer | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| B-cell lymphoma | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Basal cell carcinoma | 3/392 (0.8%) | 8 | 6/394 (1.5%) | 12 |
| Bladder cancer | 1/392 (0.3%) | 1 | 2/394 (0.5%) | 3 |
| Bladder cancer recurrent | 1/392 (0.3%) | 1 | 2/394 (0.5%) | 6 |
| Bladder transitional cell carcinoma | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Bowen's disease | 1/392 (0.3%) | 1 | 2/394 (0.5%) | 2 |
| Bronchial carcinoma | 1/392 (0.3%) | 2 | 0/394 (0%) | 0 |
| Cholangiocarcinoma | 0/392 (0%) | 0 | 1/394 (0.3%) | 2 |
| Chronic lymphocytic leukaemia | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Colon cancer | 3/392 (0.8%) | 3 | 1/394 (0.3%) | 1 |
| Gastric cancer | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 3 |
| Kaposi's sarcoma | 1/392 (0.3%) | 2 | 0/394 (0%) | 0 |
| Lung adenocarcinoma | 2/392 (0.5%) | 2 | 1/394 (0.3%) | 1 |
| Malignant melanoma | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Meningioma | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Nasal sinus cancer | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Pancreatic carcinoma | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 2 |
| Small cell lung cancer | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Squamous cell carcinoma of skin | 7/392 (1.8%) | 8 | 7/394 (1.8%) | 23 |
| Tumour pain | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Intestinal adenocarcinoma | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Colorectal cancer metastatic | 1/392 (0.3%) | 2 | 0/394 (0%) | 0 |
| Carcinoid tumour of the small bowel | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Thyroid cancer metastatic | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Lung neoplasm malignant | 0/392 (0%) | 0 | 1/394 (0.3%) | 2 |
| Non-small cell lung cancer metastatic | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Brain neoplasm | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Colorectal cancer | 2/392 (0.5%) | 3 | 0/394 (0%) | 0 |
| Hepatocellular carcinoma | 1/392 (0.3%) | 2 | 0/394 (0%) | 0 |
| Nervous system disorders | ||||
| Alexia | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Carotid artery stenosis | 0/392 (0%) | 0 | 2/394 (0.5%) | 2 |
| Cauda equina syndrome | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Cerebrovascular accident | 1/392 (0.3%) | 1 | 2/394 (0.5%) | 2 |
| Dizziness | 2/392 (0.5%) | 2 | 0/394 (0%) | 0 |
| Haemorrhage intracranial | 0/392 (0%) | 0 | 1/394 (0.3%) | 2 |
| Monoplegia | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Neuralgia | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Paraparesis | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Peripheral sensory neuropathy | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Presyncope | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Radiculopathy | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Sciatica | 2/392 (0.5%) | 3 | 0/394 (0%) | 0 |
| Seizure | 1/392 (0.3%) | 1 | 2/394 (0.5%) | 2 |
| Spinal cord compression | 7/392 (1.8%) | 7 | 9/394 (2.3%) | 9 |
| Subarachnoid haemorrhage | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Syncope | 2/392 (0.5%) | 2 | 2/394 (0.5%) | 2 |
| Transient global amnesia | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Transient ischaemic attack | 2/392 (0.5%) | 2 | 2/394 (0.5%) | 2 |
| Spinal epidural haematoma | 0/392 (0%) | 0 | 1/394 (0.3%) | 2 |
| Cognitive disorder | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Vascular dementia | 1/392 (0.3%) | 3 | 0/394 (0%) | 0 |
| Ischaemic stroke | 2/392 (0.5%) | 2 | 0/394 (0%) | 0 |
| Parkinson's disease | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Facial neuralgia | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Psychiatric disorders | ||||
| Confusional state | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Delirium | 2/392 (0.5%) | 2 | 1/394 (0.3%) | 1 |
| Depression | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Renal and urinary disorders | ||||
| Dysuria | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Haematuria | 5/392 (1.3%) | 6 | 4/394 (1%) | 5 |
| Hydronephrosis | 0/392 (0%) | 0 | 4/394 (1%) | 4 |
| Nephrolithiasis | 2/392 (0.5%) | 3 | 0/394 (0%) | 0 |
| Renal colic | 0/392 (0%) | 0 | 2/394 (0.5%) | 3 |
| Urinary bladder haemorrhage | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Urinary incontinence | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Urinary retention | 4/392 (1%) | 5 | 3/394 (0.8%) | 3 |
| Urinary tract obstruction | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Chronic kidney disease | 1/392 (0.3%) | 3 | 0/394 (0%) | 0 |
| Urethral stenosis | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Acute kidney injury | 2/392 (0.5%) | 2 | 2/394 (0.5%) | 7 |
| Ureterolithiasis | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Reproductive system and breast disorders | ||||
| Gynaecomastia | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Pelvic pain | 0/392 (0%) | 0 | 2/394 (0.5%) | 3 |
| Prostatism | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic obstructive pulmonary disease | 2/392 (0.5%) | 2 | 1/394 (0.3%) | 2 |
| Dyspnoea | 1/392 (0.3%) | 1 | 4/394 (1%) | 5 |
| Interstitial lung disease | 1/392 (0.3%) | 3 | 0/394 (0%) | 0 |
| Pleural effusion | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Pneumonia aspiration | 0/392 (0%) | 0 | 2/394 (0.5%) | 3 |
| Pneumonitis | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
| Pulmonary embolism | 6/392 (1.5%) | 7 | 2/394 (0.5%) | 2 |
| Respiratory failure | 2/392 (0.5%) | 3 | 1/394 (0.3%) | 1 |
| Lower respiratory tract inflammation | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Organising pneumonia | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Skin ulcer | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Vascular disorders | ||||
| Aortic dissection | 1/392 (0.3%) | 1 | 2/394 (0.5%) | 3 |
| Aortic stenosis | 0/392 (0%) | 0 | 1/394 (0.3%) | 1 |
| Circulatory collapse | 1/392 (0.3%) | 1 | 0/394 (0%) | 0 |
| Hypertension | 1/392 (0.3%) | 1 | 2/394 (0.5%) | 3 |
| Hypotension | 2/392 (0.5%) | 2 | 1/394 (0.3%) | 1 |
| Lymphoedema | 0/392 (0%) | 0 | 2/394 (0.5%) | 2 |
| Peripheral ischaemia | 2/392 (0.5%) | 5 | 0/394 (0%) | 0 |
| Deep vein thrombosis | 1/392 (0.3%) | 1 | 1/394 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Radium-223 Dichloride + Abi/Pred | Placebo + Abi/Pred | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 369/392 (94.1%) | 376/394 (95.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 65/392 (16.6%) | 134 | 61/394 (15.5%) | 113 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 23/392 (5.9%) | 24 | 15/394 (3.8%) | 17 |
| Constipation | 69/392 (17.6%) | 81 | 79/394 (20.1%) | 97 |
| Diarrhoea | 69/392 (17.6%) | 107 | 71/394 (18%) | 102 |
| Dyspepsia | 20/392 (5.1%) | 23 | 15/394 (3.8%) | 16 |
| Nausea | 76/392 (19.4%) | 91 | 67/394 (17%) | 74 |
| Vomiting | 40/392 (10.2%) | 48 | 40/394 (10.2%) | 45 |
| General disorders | ||||
| Asthenia | 37/392 (9.4%) | 48 | 43/394 (10.9%) | 60 |
| Fatigue | 103/392 (26.3%) | 142 | 95/394 (24.1%) | 136 |
| Influenza like illness | 12/392 (3.1%) | 16 | 20/394 (5.1%) | 24 |
| Oedema peripheral | 57/392 (14.5%) | 78 | 64/394 (16.2%) | 77 |
| Pyrexia | 28/392 (7.1%) | 33 | 34/394 (8.6%) | 49 |
| Infections and infestations | ||||
| Influenza | 22/392 (5.6%) | 23 | 13/394 (3.3%) | 21 |
| Nasopharyngitis | 31/392 (7.9%) | 40 | 38/394 (9.6%) | 53 |
| Upper respiratory tract infection | 28/392 (7.1%) | 39 | 33/394 (8.4%) | 43 |
| Urinary tract infection | 39/392 (9.9%) | 54 | 31/394 (7.9%) | 38 |
| Injury, poisoning and procedural complications | ||||
| Fall | 60/392 (15.3%) | 87 | 50/394 (12.7%) | 70 |
| Traumatic fracture | 42/392 (10.7%) | 72 | 23/394 (5.8%) | 48 |
| Contusion | 28/392 (7.1%) | 38 | 31/394 (7.9%) | 37 |
| Investigations | ||||
| Alanine aminotransferase increased | 69/392 (17.6%) | 180 | 61/394 (15.5%) | 149 |
| Aspartate aminotransferase increased | 61/392 (15.6%) | 127 | 55/394 (14%) | 104 |
| Weight decreased | 20/392 (5.1%) | 32 | 24/394 (6.1%) | 34 |
| Metabolism and nutrition disorders | ||||
| Hyperglycaemia | 12/392 (3.1%) | 18 | 23/394 (5.8%) | 50 |
| Hypokalaemia | 43/392 (11%) | 76 | 43/394 (10.9%) | 75 |
| Decreased appetite | 65/392 (16.6%) | 82 | 52/394 (13.2%) | 54 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 91/392 (23.2%) | 133 | 88/394 (22.3%) | 155 |
| Back pain | 151/392 (38.5%) | 250 | 138/394 (35%) | 209 |
| Bone pain | 69/392 (17.6%) | 96 | 76/394 (19.3%) | 100 |
| Muscle spasms | 27/392 (6.9%) | 32 | 30/394 (7.6%) | 34 |
| Muscular weakness | 25/392 (6.4%) | 39 | 36/394 (9.1%) | 50 |
| Musculoskeletal pain | 46/392 (11.7%) | 55 | 47/394 (11.9%) | 58 |
| Myalgia | 25/392 (6.4%) | 29 | 23/394 (5.8%) | 26 |
| Neck pain | 17/392 (4.3%) | 18 | 24/394 (6.1%) | 30 |
| Osteoporosis | 27/392 (6.9%) | 28 | 1/394 (0.3%) | 1 |
| Osteoporotic fracture | 26/392 (6.6%) | 75 | 1/394 (0.3%) | 1 |
| Pain in extremity | 52/392 (13.3%) | 73 | 58/394 (14.7%) | 80 |
| Pathological fracture | 48/392 (12.2%) | 68 | 26/394 (6.6%) | 40 |
| Musculoskeletal chest pain | 28/392 (7.1%) | 41 | 31/394 (7.9%) | 39 |
| Spinal pain | 30/392 (7.7%) | 35 | 27/394 (6.9%) | 34 |
| Nervous system disorders | ||||
| Dizziness | 45/392 (11.5%) | 54 | 35/394 (8.9%) | 41 |
| Headache | 30/392 (7.7%) | 45 | 31/394 (7.9%) | 39 |
| Psychiatric disorders | ||||
| Insomnia | 32/392 (8.2%) | 35 | 25/394 (6.3%) | 26 |
| Renal and urinary disorders | ||||
| Haematuria | 31/392 (7.9%) | 44 | 21/394 (5.3%) | 28 |
| Reproductive system and breast disorders | ||||
| Pelvic pain | 12/392 (3.1%) | 16 | 21/394 (5.3%) | 31 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 36/392 (9.2%) | 42 | 41/394 (10.4%) | 50 |
| Dyspnoea | 20/392 (5.1%) | 28 | 31/394 (7.9%) | 35 |
| Vascular disorders | ||||
| Hypertension | 61/392 (15.6%) | 164 | 80/394 (20.3%) | 213 |
| Hot flush | 23/392 (5.9%) | 25 | 51/394 (12.9%) | 53 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Therapeutic Area Head |
|---|---|
| Organization | Bayer |
| Phone | 1-888-8422937 |
| clinical-trials-contact@bayer.com |
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT02043678
Other Study ID Numbers:
- 15396
- 2013-003438-33
First Posted:
Jan 23, 2014
Last Update Posted:
Aug 17, 2022
Last Verified:
Aug 1, 2022