A Randomized Phase IIa Efficacy and Safety Study of Radium-223 Dichloride With Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (CRPC)
Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT02034552
Collaborator
(none)
68
19
3
51.6
3.6
0.1
Study Details
Study Description
Brief Summary
The primary objective in this study is to evaluate bone scan response at Week 24 based on the quantified technetium-99 bone scan lesion area (BSLA). The safety of radium-223 dichloride in combination with abiraterone acetate or enzalutamide will be investigated. The study will evaluate radiological progression free survival, overall survival, and skeletal events. This study will also explore the clinical utility of different imaging modalities (whole body quantified technetium-99 bone scan, DW-MRI [diffusion-weighted magnetic resonance imaging] and NaF [sodium fluoride] PET-CT [positron emission tomography-computed tomography] scan) and will have a separate central radiological review for applicable secondary and exploratory imaging endpoints. All subjects will be randomized as assigned randomly by the IXRS (interactive voice / web response system) system in a 1:1:1 ratio into one of the treatment arms: radium-223 dichloride alone, 50 kBq/kg (55 kBq/kg after implementation of NIST [National Institute of Standards and Technology] update) every 4 weeks for up to 6 doses; radium-223 dichloride, 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks up to 6 doses together with abiraterone acetate 1,000 mg daily and prednisone 5 mg bid (twice daily); radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks up to 6 doses together with enzalutamide 160 mg daily. The study will consist of screening, treatment and follow-up periods. Study will continue until disease progression as determined by investigator, or when patient meets criteria for withdrawal from study. Subjects in treatment arms with abiraterone/prednisone or enzalutamide will have the option to continue taking oral study therapy until the end of the study (2 years from the last dose of radium-223 dichloride) if the investigator deems the subject may benefit and there is no clinical or radiological progression. Subjects who discontinue all study treatment prior to 2 years from last radium-223 dichloride treatment will enter active follow-up. During the active follow-up period, the subject will have a safety visit at the clinic every 12 weeks from the EOT (end of treatment) for up to 2 years from the last dose of radium-223 dichloride. Beyond 2 years from last radium-223 dichloride treatment,subjects will enter long-term follow-up and will be followed via phone contact at intervals to assess for safety (hematological toxicity and new primary malignancies) and overall survival. A separate long-term safety follow-up study protocol is planned. Once implemented, the study subjects surviving after the end of the active follow-up will be transitioned to this separate long-term safety follow-up protocol.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
68 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Open-label Phase IIa Study Evaluating Quantified Bone Scan Response Following Treatment With Radium-223 Dichloride Alone or in Combination With Abiraterone Acetate or Enzalutamide in Subjects With Castration-resistant Prostate Cancer Who Have Bone Metastases
Actual Study Start Date
:
Mar 7, 2014
Actual Primary Completion Date
:
Jul 15, 2016
Actual Study Completion Date
:
Jun 26, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Radium-223 dichloride (Xofigo, BAY88-8223)
|
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Radium-223 dichloride (Xofigo, BAY88-8223) 50 kBq/kg (55 kBq/kg after implementation of NIST [National Institute of Standards and Technology] update) every 4 weeks x 6 doses intravenous slow bolus
|
| Experimental: Radium-223 with abiraterone&prednisone
|
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Radium-223 dichloride (Xofigo, BAY88-8223) 50 kBq/kg (55 kBq/kg after implementation of NIST [National Institute of Standards and Technology] update) every 4 weeks x 6 doses intravenous slow bolus
Drug: Abiraterone acetate
Abiraterone acetate 1000 mg (4 x 250 mg tablets) taken orally once daily for up to two years following last dose of radium-223 dichloride
Drug: Prednisone
Prednisone 5 mg capsule taken orally twice daily for up to two years following last dose of radium-223 dichloride
|
| Experimental: Radium-223 with enzalutamide
|
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Radium-223 dichloride (Xofigo, BAY88-8223) 50 kBq/kg (55 kBq/kg after implementation of NIST [National Institute of Standards and Technology] update) every 4 weeks x 6 doses intravenous slow bolus
Drug: Enzalutamide
Enzalutamide 160 mg (four 40 mg capsules) taken orally once daily for up to two years following last dose of radium-223 dichloride
|
Outcome Measures
Primary Outcome Measures
- Patient Bone Scan Response Rate [At 24 weeks]
Radiological bone scan response based on change from baseline of digitized technetium-99 bone scans using computer-aided detection software. Responder (R): 30% or greater resolution of the BSLA compared to baseline. Stable Disease (SD): Not meeting the criteria for R, PD, or UE. Progressive Disease (PD): Two or more new areas of radiotracer uptake attributable to metastatic disease in regions of bone that had not previously shown radiotracer uptake or greater than 30% increase from baseline in BSLA attributable to metastatic disease. Unable to Evaluate (UE): Assigned if bone scan results cannot be interpreted due to inconsistent image acquisition parameters compared to the reference scan, incomplete imaging, or other similar technical deficiencies.
- Bone Scan Lesion Area [At 24 weeks]
Bone scan lesion area was defined as the sum of the pixel areas (cm2) of the set of the whole body technetium-99 bone scan imaging pixels identified as bone lesion.
Secondary Outcome Measures
- Radiological Progression Free Survival [From randomization to radiological disease progression or death from any cause (about 30.82 months )]
- Time to Radiological Progression [From the randomization date to the date of radiological disease progression (about 30.82months)]
- Time to Radiological Bone Progression [From the randomization date to the date of radiological bone progression (about 30.82 months)]
- Time to First Symptomatic Skeletal Event [From the randomization date to the first SSE on or following the randomization date (about 30.82 months)]
- Symptomatic Skeletal Event-free Survival [From the randomization date to the first SSE on or following the randomization date or death, whichever occurred first (about 32.39 months)]
- Overall Survival [From the randomization date to the date of death due to any cause (about 42.94 months)]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histologically or cytologically confirmed adenocarcinoma of the prostate
-
Known castration-resistant disease
-
Serum PSA ≥2 ng/mL (μg/L)
-
Multiple skeletal metastases (≥2 hot spots) on bone scan
-
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2.
-
Life expectancy ≥6 months
-
Adequate hematologic, hepatic, and renal function
Exclusion Criteria:
-
History of visceral metastasis, or visceral metastases
-
Malignant lymphadenopathy with lymph nodes exceeding 3 cm in short axis diameter
-
Medical condition that would make prednisone (corticosteroid) use contraindicated
-
Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone bid
-
Treatment with more than one chemotherapy agent for prostate cancer
-
Prior systemic radiotherapy and hemibody external radiotherapy
-
History of pituitary or adrenal dysfunction
-
Chronic conditions associated with non-malignant abnormal bone growth (e.g., confirmed Paget's disease of bone)
-
Atrial fibrillation, or other cardiac arrhythmia requiring medical therapy
-
History of seizures (taking/not taking anticonvulsants), arteriovenous malformation in the brain, head trauma with loss of consciousness
-
Central nervous system (CNS) metastases
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Scottsdale | Arizona | United States | 85251 | |
| 2 | Tucson | Arizona | United States | 85704 | |
| 3 | Los Angeles | California | United States | 90033 | |
| 4 | New Haven | Connecticut | United States | 06520 | |
| 5 | Newark | Delaware | United States | 19713 | |
| 6 | Washington | District of Columbia | United States | 20007 | |
| 7 | Plantation | Florida | United States | 33324 | |
| 8 | Indianapolis | Indiana | United States | 46202 | |
| 9 | New Orleans | Louisiana | United States | 70112 | |
| 10 | Shreveport | Louisiana | United States | 71103 | |
| 11 | Rockville | Maryland | United States | 20850 | |
| 12 | Detroit | Michigan | United States | 48201 | |
| 13 | Saint Louis | Missouri | United States | 63110 | |
| 14 | Omaha | Nebraska | United States | 68130 | |
| 15 | Bronx | New York | United States | 10467-2490 | |
| 16 | Syracuse | New York | United States | 13210 | |
| 17 | Springfield | Oregon | United States | 97477 | |
| 18 | Houston | Texas | United States | 77027 | |
| 19 | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- Bayer
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT02034552
Other Study ID Numbers:
- 16544
First Posted:
Jan 13, 2014
Last Update Posted:
Jul 23, 2019
Last Verified:
Jul 1, 2019
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Study was conducted at 19 study centers in USA from 7-Mar-2014 (first subject's first visit) to 26-Jun-2018 (last subject's last visit). |
|---|---|
| Pre-assignment Detail | Overall, 103 subjects were screened. Of them, 68 subjects were randomized, and 63 subjects were received study treatment. |
| Arm/Group Title | Radium-223 Dichloride (Xofigo, BAY88-8223) | Radium-223 With Abiraterone & Prednision | Radium-223 With Enzalutamide |
|---|---|---|---|
| Arm/Group Description | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus). | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. |
| Period Title: Overall Study | |||
| STARTED | 22 | 24 | 22 |
| Received Treatment | 19 | 22 | 22 |
| COMPLETED | 8 | 4 | 5 |
| NOT COMPLETED | 14 | 20 | 17 |
Baseline Characteristics
| Arm/Group Title | Radium-223 Dichloride (Xofigo, BAY88-8223) | Radium-223 With Abiraterone & Prednision | Radium-223 With Enzalutamide | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus). | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. | Total of all reporting groups |
| Overall Participants | 22 | 24 | 22 | 68 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
71.5
(10.2)
|
68.6
(8.6)
|
71.0
(8.7)
|
70.3
(9.1)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
22
100%
|
24
100%
|
22
100%
|
68
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
1
4.5%
|
1
4.2%
|
1
4.5%
|
3
4.4%
|
| Not Hispanic or Latino |
21
95.5%
|
23
95.8%
|
20
90.9%
|
64
94.1%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
1
4.5%
|
1
1.5%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
4.5%
|
2
8.3%
|
0
0%
|
3
4.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
9.1%
|
5
20.8%
|
3
13.6%
|
10
14.7%
|
| White |
18
81.8%
|
17
70.8%
|
17
77.3%
|
52
76.5%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
4.5%
|
0
0%
|
2
9.1%
|
3
4.4%
|
| Eastern Cooperative Oncology Group (Count of Participants) | ||||
| Missing |
3
13.6%
|
2
8.3%
|
0
0%
|
5
7.4%
|
| PS 0 |
10
45.5%
|
13
54.2%
|
11
50%
|
34
50%
|
| PS1 |
9
40.9%
|
9
37.5%
|
11
50%
|
29
42.6%
|
Outcome Measures
| Title | Patient Bone Scan Response Rate |
|---|---|
| Description | Radiological bone scan response based on change from baseline of digitized technetium-99 bone scans using computer-aided detection software. Responder (R): 30% or greater resolution of the BSLA compared to baseline. Stable Disease (SD): Not meeting the criteria for R, PD, or UE. Progressive Disease (PD): Two or more new areas of radiotracer uptake attributable to metastatic disease in regions of bone that had not previously shown radiotracer uptake or greater than 30% increase from baseline in BSLA attributable to metastatic disease. Unable to Evaluate (UE): Assigned if bone scan results cannot be interpreted due to inconsistent image acquisition parameters compared to the reference scan, incomplete imaging, or other similar technical deficiencies. |
| Time Frame | At 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Imaging endpt analysis set (IMG): consists of mITT subj. (ITT subj. who received at least one dose of each study drug as randomized) with evaluable imaging scan at baseline, eg. bl quantitated technetium-99 bone scan imaging of sufficient completeness and quality to be assessable and having a non-zero BSLA, as determ. by the central reviewer. |
| Arm/Group Title | Radium-223 Dichloride (Xofigo, BAY88-8223) | Radium-223 With Abiraterone & Prednision | Radium-223 With Enzalutamide |
|---|---|---|---|
| Arm/Group Description | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus). | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. |
| Measure Participants | 18 | 19 | 16 |
| Responder (R) |
22.2
|
57.9
|
50.0
|
| Stable Disease (SD) |
0
|
21.1
|
18.8
|
| Progressive Disease (PD) |
27.8
|
5.3
|
12.5
|
| Missing |
50.0
|
15.8
|
18.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Radium-223 Dichloride (Xofigo, BAY88-8223) |
|---|---|---|
| Comments | H0: Patient bone scan response rate at Week 24 ≤5%. The Type I error rate for the test in each treatment group, is one-sided 0.10. A one-sided p-value will be reported for this test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0109 |
| Comments | [80% CI]: [10.1%- 39.6%] | |
| Method | Clopper and Pearson | |
| Comments | Patient bone scan response rate at Week 24 will be estimated with exact binomial 80% CI using the method of Clopper and Pearson. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Radium-223 With Abiraterone & Prednision |
|---|---|---|
| Comments | H0: Patient bone scan response rate at Week 24 ≤5%. The Type I error rate for the test in each treatment group, is one-sided 0.10. A one-sided p-value will be reported for this test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | [80% CI]: [40.8% - 73.7%] | |
| Method | Clopper and Pearson | |
| Comments | Patient bone scan response rate at Week 24 will be estimated with exact binomial 80% CI using the method of Clopper and Pearson. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Radium-223 With Enzalutamide |
|---|---|---|
| Comments | H0: Patient bone scan response rate at Week 24 ≤5%. The Type I error rate for the test in each treatment group, is one-sided 0.10. A one-sided p-value will be reported for this test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | [80% CI]: [31.8% - 68.2%] | |
| Method | Clopper and Pearson | |
| Comments | Patient bone scan response rate at Week 24 will be estimated with exact binomial 80% CI using the method of Clopper and Pearson. | |
| Title | Bone Scan Lesion Area |
|---|---|
| Description | Bone scan lesion area was defined as the sum of the pixel areas (cm2) of the set of the whole body technetium-99 bone scan imaging pixels identified as bone lesion. |
| Time Frame | At 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Imaging endpt analysis set (IMG): consists of mITT subj. (ITT subj. who received at least one dose of each study drug as randomized) with evaluable imaging scan at baseline, eg. bl quantitated technetium-99 bone scan imaging of sufficient completeness and quality to be assessable and having a non-zero BSLA, as determ. by the central reviewer. |
| Arm/Group Title | Radium-223 Dichloride (Xofigo, BAY88-8223) | Radium-223 With Abiraterone & Prednision | Radium-223 With Enzalutamide |
|---|---|---|---|
| Arm/Group Description | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus). | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. |
| Measure Participants | 18 | 19 | 16 |
| Mean (Standard Deviation) [cm^2] |
30227.13
(64912.24)
|
10185.58
(12407.65)
|
17321.45
(22577.59)
|
| Title | Radiological Progression Free Survival |
|---|---|
| Description | |
| Time Frame | From randomization to radiological disease progression or death from any cause (about 30.82 months ) |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT analysis set: Included all ITT subjects who received at least one dose of each study drug as randomized. |
| Arm/Group Title | Radium-223 Dichloride (Xofigo, BAY88-8223) | Radium-223 With Abiraterone & Prednision | Radium-223 With Enzalutamide |
|---|---|---|---|
| Arm/Group Description | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus). | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. |
| Measure Participants | 19 | 22 | 22 |
| Median (80% Confidence Interval) [Months] |
4.40
|
NA
|
NA
|
| Title | Time to Radiological Progression |
|---|---|
| Description | |
| Time Frame | From the randomization date to the date of radiological disease progression (about 30.82months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Radium-223 Dichloride (Xofigo, BAY88-8223) | Radium-223 With Abiraterone & Prednision | Radium-223 With Enzalutamide |
|---|---|---|---|
| Arm/Group Description | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus). | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. |
| Measure Participants | 19 | 22 | 22 |
| Median (80% Confidence Interval) [Months] |
4.40
|
NA
|
NA
|
| Title | Time to Radiological Bone Progression |
|---|---|
| Description | |
| Time Frame | From the randomization date to the date of radiological bone progression (about 30.82 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Radium-223 Dichloride (Xofigo, BAY88-8223) | Radium-223 With Abiraterone & Prednision | Radium-223 With Enzalutamide |
|---|---|---|---|
| Arm/Group Description | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus). | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. |
| Measure Participants | 19 | 22 | 22 |
| Median (80% Confidence Interval) [Months] |
11.5
|
NA
|
NA
|
| Title | Time to First Symptomatic Skeletal Event |
|---|---|
| Description | |
| Time Frame | From the randomization date to the first SSE on or following the randomization date (about 30.82 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT analysis set: Included all ITT subjects who received at least one dose of each study drug as randomized. |
| Arm/Group Title | Radium-223 Dichloride (Xofigo, BAY88-8223) | Radium-223 With Abiraterone & Prednision | Radium-223 With Enzalutamide |
|---|---|---|---|
| Arm/Group Description | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus). | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. |
| Measure Participants | 19 | 22 | 22 |
| Median (80% Confidence Interval) [Months] |
NA
|
NA
|
NA
|
| Title | Symptomatic Skeletal Event-free Survival |
|---|---|
| Description | |
| Time Frame | From the randomization date to the first SSE on or following the randomization date or death, whichever occurred first (about 32.39 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT analysis set: Included all ITT subjects who received at least one dose of each study drug as randomized. |
| Arm/Group Title | Radium-223 Dichloride (Xofigo, BAY88-8223) | Radium-223 With Abiraterone & Prednision | Radium-223 With Enzalutamide |
|---|---|---|---|
| Arm/Group Description | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus). | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. |
| Measure Participants | 19 | 22 | 22 |
| Median (80% Confidence Interval) [Months] |
11.93
|
NA
|
19.91
|
| Title | Overall Survival |
|---|---|
| Description | |
| Time Frame | From the randomization date to the date of death due to any cause (about 42.94 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT analysis set: Included all ITT subjects who received at least one dose of each study drug as randomized. |
| Arm/Group Title | Radium-223 Dichloride (Xofigo, BAY88-8223) | Radium-223 With Abiraterone & Prednision | Radium-223 With Enzalutamide |
|---|---|---|---|
| Arm/Group Description | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus). | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. | Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection. |
| Measure Participants | 19 | 22 | 22 |
| Median (80% Confidence Interval) [Months] |
35.81
|
37.55
|
29.86
|
Adverse Events
| Time Frame | All AEs occurring from the time the subject signs the ICF until 30 days after the last dose of any study medication (about 18 months). | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Radium-223 | Radium-223 + Abiraterone Acetate + Prednisone | Radium-223 + Enzalutamide | |||
| Arm/Group Description | Radium-223 | Radium-223 + Abiraterone Acetate + Prednisone | Radium-223 + Enzalutamide | |||
All Cause Mortality |
||||||
| Radium-223 | Radium-223 + Abiraterone Acetate + Prednisone | Radium-223 + Enzalutamide | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/19 (0%) | 0/22 (0%) | 1/22 (4.5%) | |||
Serious Adverse Events |
||||||
| Radium-223 | Radium-223 + Abiraterone Acetate + Prednisone | Radium-223 + Enzalutamide | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/19 (10.5%) | 10/22 (45.5%) | 8/22 (36.4%) | |||
| Cardiac disorders | ||||||
| Cardiac failure congestive | 0/19 (0%) | 0 | 1/22 (4.5%) | 2 | 0/22 (0%) | 0 |
| Cardiac failure congestive | 0/19 (0%) | 0 | 1/22 (4.5%) | 2 | 0/22 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Nausea | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Nausea | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| General disorders | ||||||
| General physical health deterioration | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Chest pain | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| General physical health deterioration | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Infections and infestations | ||||||
| Pneumonia | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Pneumonia | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Tooth abscess | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Fall | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Subdural haematoma | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Fall | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Subdural haematoma | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 2/19 (10.5%) | 3 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Hypocalcaemia | 1/19 (5.3%) | 8 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Dehydration | 2/19 (10.5%) | 3 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Hypocalcaemia | 1/19 (5.3%) | 8 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Back pain | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 1/22 (4.5%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Squamous cell carcinoma of skin | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Basal cell carcinoma | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Squamous cell carcinoma of skin | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Nervous system disorders | ||||||
| Dizziness | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Syncope | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 3/22 (13.6%) | 3 |
| Dizziness | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Syncope | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 3/22 (13.6%) | 3 |
| Renal and urinary disorders | ||||||
| Haematuria | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Acute kidney injury | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Haematuria | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Acute kidney injury | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pulmonary embolism | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Pulmonary embolism | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Radium-223 | Radium-223 + Abiraterone Acetate + Prednisone | Radium-223 + Enzalutamide | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/19 (94.7%) | 22/22 (100%) | 22/22 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 3/19 (15.8%) | 7 | 3/22 (13.6%) | 5 | 3/22 (13.6%) | 5 |
| Leukopenia | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Neutropenia | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Thrombocytopenia | 0/19 (0%) | 0 | 1/22 (4.5%) | 2 | 0/22 (0%) | 0 |
| Anaemia | 3/19 (15.8%) | 7 | 4/22 (18.2%) | 6 | 4/22 (18.2%) | 6 |
| Cardiac disorders | ||||||
| Angina pectoris | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Cardiac disorder | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Angina pectoris | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Ear and labyrinth disorders | ||||||
| Tinnitus | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Vertigo | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Tinnitus | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Vertigo | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Endocrine disorders | ||||||
| Hypothyroidism | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Hypothyroidism | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 0/22 (0%) | 0 |
| Eye disorders | ||||||
| Cataract | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Conjunctivitis allergic | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Diplopia | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Eyelid ptosis | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Vision blurred | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Visual impairment | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Vision blurred | 0/19 (0%) | 0 | 2/22 (9.1%) | 3 | 0/22 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Abdominal distension | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Abdominal pain | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 0/22 (0%) | 0 |
| Abdominal pain lower | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 0/22 (0%) | 0 |
| Abdominal pain upper | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Constipation | 1/19 (5.3%) | 2 | 5/22 (22.7%) | 7 | 2/22 (9.1%) | 2 |
| Diarrhoea | 4/19 (21.1%) | 7 | 8/22 (36.4%) | 15 | 8/22 (36.4%) | 12 |
| Dry mouth | 2/19 (10.5%) | 2 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Dyspepsia | 0/19 (0%) | 0 | 4/22 (18.2%) | 4 | 0/22 (0%) | 0 |
| Dysphagia | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Faeces discoloured | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Gastrooesophageal reflux disease | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 1/22 (4.5%) | 1 |
| Gingival bleeding | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Haematochezia | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Mouth haemorrhage | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Nausea | 2/19 (10.5%) | 4 | 9/22 (40.9%) | 11 | 5/22 (22.7%) | 5 |
| Toothache | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Vomiting | 2/19 (10.5%) | 2 | 5/22 (22.7%) | 5 | 1/22 (4.5%) | 1 |
| Anorectal discomfort | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Abdominal discomfort | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Abdominal distension | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Abdominal pain | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Abdominal pain lower | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 0/22 (0%) | 0 |
| Abdominal pain upper | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Constipation | 1/19 (5.3%) | 1 | 6/22 (27.3%) | 8 | 3/22 (13.6%) | 4 |
| Diarrhoea | 4/19 (21.1%) | 7 | 8/22 (36.4%) | 16 | 9/22 (40.9%) | 14 |
| Dry mouth | 2/19 (10.5%) | 2 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Dyspepsia | 0/19 (0%) | 0 | 4/22 (18.2%) | 4 | 0/22 (0%) | 0 |
| Gingival bleeding | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Haematochezia | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Mouth haemorrhage | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Nausea | 2/19 (10.5%) | 4 | 9/22 (40.9%) | 12 | 6/22 (27.3%) | 6 |
| Vomiting | 2/19 (10.5%) | 2 | 6/22 (27.3%) | 6 | 1/22 (4.5%) | 1 |
| Anorectal discomfort | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| General disorders | ||||||
| Asthenia | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 3/22 (13.6%) | 3 |
| Chest discomfort | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Chest pain | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 2/22 (9.1%) | 2 |
| Chills | 1/19 (5.3%) | 1 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Cyst | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 3 |
| Face oedema | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Fatigue | 6/19 (31.6%) | 9 | 5/22 (22.7%) | 7 | 8/22 (36.4%) | 10 |
| Gait disturbance | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Influenza like illness | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Injection site pain | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Oedema | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Oedema peripheral | 0/19 (0%) | 0 | 3/22 (13.6%) | 4 | 1/22 (4.5%) | 1 |
| Pyrexia | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Peripheral swelling | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 2/22 (9.1%) | 2 |
| Early satiety | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Asthenia | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 3/22 (13.6%) | 3 |
| Chest pain | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 2/22 (9.1%) | 2 |
| Chills | 1/19 (5.3%) | 1 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Fatigue | 6/19 (31.6%) | 9 | 8/22 (36.4%) | 11 | 9/22 (40.9%) | 11 |
| Influenza like illness | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Oedema peripheral | 0/19 (0%) | 0 | 4/22 (18.2%) | 5 | 2/22 (9.1%) | 2 |
| Pyrexia | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 0/22 (0%) | 0 |
| Peripheral swelling | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 2/22 (9.1%) | 2 |
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Infections and infestations | ||||||
| Bronchitis | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Fungal skin infection | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Gastroenteritis viral | 0/19 (0%) | 0 | 1/22 (4.5%) | 2 | 0/22 (0%) | 0 |
| Influenza | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Lower respiratory tract infection | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Nasopharyngitis | 1/19 (5.3%) | 1 | 3/22 (13.6%) | 3 | 2/22 (9.1%) | 2 |
| Onychomycosis | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Pneumonia | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Pyelonephritis | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Tinea pedis | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Tooth abscess | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Upper respiratory tract infection | 0/19 (0%) | 0 | 3/22 (13.6%) | 3 | 1/22 (4.5%) | 1 |
| Urinary tract infection | 0/19 (0%) | 0 | 3/22 (13.6%) | 4 | 0/22 (0%) | 0 |
| Bronchitis | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 2/22 (9.1%) | 2 |
| Influenza | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Lower respiratory tract infection | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 0/22 (0%) | 0 |
| Nasopharyngitis | 1/19 (5.3%) | 1 | 4/22 (18.2%) | 4 | 2/22 (9.1%) | 2 |
| Tooth abscess | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 2/22 (9.1%) | 2 |
| Upper respiratory tract infection | 0/19 (0%) | 0 | 5/22 (22.7%) | 5 | 2/22 (9.1%) | 2 |
| Urinary tract infection | 0/19 (0%) | 0 | 3/22 (13.6%) | 4 | 0/22 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Fall | 2/19 (10.5%) | 2 | 1/22 (4.5%) | 1 | 4/22 (18.2%) | 4 |
| Radius fracture | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Rib fracture | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Spinal compression fracture | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 2 |
| Subarachnoid haemorrhage | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Thoracic vertebral fracture | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Contusion | 1/19 (5.3%) | 1 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Bone contusion | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Procedural nausea | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Eye contusion | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Accident | 0/19 (0%) | 0 | 3/22 (13.6%) | 5 | 2/22 (9.1%) | 3 |
| Fall | 2/19 (10.5%) | 2 | 1/22 (4.5%) | 1 | 4/22 (18.2%) | 4 |
| Traumatic fracture | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 2/22 (9.1%) | 3 |
| Contusion | 1/19 (5.3%) | 1 | 1/22 (4.5%) | 1 | 1/22 (4.5%) | 1 |
| Investigations | ||||||
| Alanine aminotransferase increased | 0/19 (0%) | 0 | 2/22 (9.1%) | 5 | 2/22 (9.1%) | 4 |
| Aspartate aminotransferase increased | 0/19 (0%) | 0 | 2/22 (9.1%) | 3 | 2/22 (9.1%) | 2 |
| Blood bilirubin increased | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 2 |
| Blood creatine phosphokinase increased | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Blood potassium decreased | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Heart rate increased | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Lymphocyte count decreased | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 4 |
| Neutrophil count decreased | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Platelet count decreased | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 2 |
| Weight decreased | 3/19 (15.8%) | 3 | 1/22 (4.5%) | 1 | 3/22 (13.6%) | 3 |
| Weight increased | 1/19 (5.3%) | 2 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Alanine aminotransferase increased | 0/19 (0%) | 0 | 2/22 (9.1%) | 5 | 2/22 (9.1%) | 4 |
| Aspartate aminotransferase increased | 0/19 (0%) | 0 | 2/22 (9.1%) | 3 | 2/22 (9.1%) | 3 |
| Blood potassium decreased | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Platelet count decreased | 0/19 (0%) | 0 | 3/22 (13.6%) | 4 | 1/22 (4.5%) | 3 |
| Weight decreased | 3/19 (15.8%) | 3 | 1/22 (4.5%) | 1 | 3/22 (13.6%) | 3 |
| Weight increased | 1/19 (5.3%) | 2 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Diabetes mellitus | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Gout | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Hypercalcaemia | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Hyperglycaemia | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Hypocalcaemia | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Hypokalaemia | 1/19 (5.3%) | 3 | 4/22 (18.2%) | 4 | 0/22 (0%) | 0 |
| Hypomagnesaemia | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Hyponatraemia | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 1/22 (4.5%) | 1 |
| Hypophosphataemia | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Vitamin B12 deficiency | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Decreased appetite | 3/19 (15.8%) | 3 | 3/22 (13.6%) | 6 | 5/22 (22.7%) | 5 |
| Gout | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Hyperglycaemia | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Hypokalaemia | 1/19 (5.3%) | 3 | 4/22 (18.2%) | 4 | 1/22 (4.5%) | 1 |
| Decreased appetite | 3/19 (15.8%) | 3 | 3/22 (13.6%) | 6 | 5/22 (22.7%) | 5 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 3/19 (15.8%) | 3 | 2/22 (9.1%) | 3 | 4/22 (18.2%) | 4 |
| Arthritis | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Back pain | 5/19 (26.3%) | 7 | 5/22 (22.7%) | 9 | 9/22 (40.9%) | 12 |
| Bone pain | 0/19 (0%) | 0 | 3/22 (13.6%) | 4 | 0/22 (0%) | 0 |
| Flank pain | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 1/22 (4.5%) | 1 |
| Groin pain | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Muscle spasms | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Muscular weakness | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Musculoskeletal pain | 1/19 (5.3%) | 1 | 2/22 (9.1%) | 3 | 2/22 (9.1%) | 2 |
| Myalgia | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Neck pain | 0/19 (0%) | 0 | 1/22 (4.5%) | 2 | 3/22 (13.6%) | 3 |
| Osteoporosis | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Pain in extremity | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 3/22 (13.6%) | 3 |
| Pain in jaw | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Pathological fracture | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Musculoskeletal chest pain | 1/19 (5.3%) | 1 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Musculoskeletal discomfort | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Limb discomfort | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Osteonecrosis of jaw | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Spinal pain | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Arthralgia | 3/19 (15.8%) | 3 | 5/22 (22.7%) | 8 | 6/22 (27.3%) | 9 |
| Back pain | 5/19 (26.3%) | 7 | 8/22 (36.4%) | 13 | 9/22 (40.9%) | 17 |
| Bone pain | 0/19 (0%) | 0 | 3/22 (13.6%) | 4 | 0/22 (0%) | 0 |
| Muscular weakness | 1/19 (5.3%) | 1 | 2/22 (9.1%) | 2 | 0/22 (0%) | 0 |
| Musculoskeletal pain | 1/19 (5.3%) | 1 | 3/22 (13.6%) | 4 | 4/22 (18.2%) | 4 |
| Neck pain | 0/19 (0%) | 0 | 1/22 (4.5%) | 2 | 3/22 (13.6%) | 3 |
| Pain in extremity | 0/19 (0%) | 0 | 3/22 (13.6%) | 7 | 4/22 (18.2%) | 6 |
| Pathological fracture | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 2/22 (9.1%) | 3 |
| Musculoskeletal chest pain | 1/19 (5.3%) | 1 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Spinal pain | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Seborrhoeic keratosis | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Nervous system disorders | ||||||
| Akathisia | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Amnesia | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Disturbance in attention | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Dizziness | 1/19 (5.3%) | 1 | 3/22 (13.6%) | 3 | 6/22 (27.3%) | 8 |
| Dysarthria | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Dysgeusia | 1/19 (5.3%) | 1 | 2/22 (9.1%) | 2 | 4/22 (18.2%) | 6 |
| Headache | 1/19 (5.3%) | 1 | 4/22 (18.2%) | 4 | 1/22 (4.5%) | 1 |
| Hypoaesthesia | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Lethargy | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Neuropathy peripheral | 2/19 (10.5%) | 2 | 1/22 (4.5%) | 1 | 1/22 (4.5%) | 1 |
| Peripheral motor neuropathy | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Spinal cord compression | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Syncope | 1/19 (5.3%) | 1 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Poor quality sleep | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Dizziness | 1/19 (5.3%) | 1 | 3/22 (13.6%) | 3 | 6/22 (27.3%) | 8 |
| Dysgeusia | 1/19 (5.3%) | 1 | 2/22 (9.1%) | 2 | 4/22 (18.2%) | 6 |
| Headache | 1/19 (5.3%) | 1 | 5/22 (22.7%) | 5 | 1/22 (4.5%) | 1 |
| Hypoaesthesia | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 2/22 (9.1%) | 3 |
| Neuropathy peripheral | 2/19 (10.5%) | 2 | 1/22 (4.5%) | 1 | 2/22 (9.1%) | 3 |
| Peripheral motor neuropathy | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Syncope | 1/19 (5.3%) | 1 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Psychiatric disorders | ||||||
| Anxiety | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Apathy | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Confusional state | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 2/22 (9.1%) | 2 |
| Depression | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Insomnia | 1/19 (5.3%) | 1 | 1/22 (4.5%) | 1 | 2/22 (9.1%) | 2 |
| Middle insomnia | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Confusional state | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 2/22 (9.1%) | 2 |
| Insomnia | 1/19 (5.3%) | 1 | 1/22 (4.5%) | 1 | 2/22 (9.1%) | 2 |
| Renal and urinary disorders | ||||||
| Calculus bladder | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Calculus urinary | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 2 |
| Haematuria | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 0/22 (0%) | 0 |
| Hydronephrosis | 1/19 (5.3%) | 2 | 0/22 (0%) | 0 | 1/22 (4.5%) | 2 |
| Obstructive uropathy | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Pollakiuria | 1/19 (5.3%) | 1 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Urge incontinence | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Urinary incontinence | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Cystitis noninfective | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Acute kidney injury | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Haematuria | 0/19 (0%) | 0 | 2/22 (9.1%) | 2 | 0/22 (0%) | 0 |
| Hydronephrosis | 1/19 (5.3%) | 2 | 0/22 (0%) | 0 | 1/22 (4.5%) | 2 |
| Pollakiuria | 1/19 (5.3%) | 1 | 2/22 (9.1%) | 2 | 1/22 (4.5%) | 1 |
| Urinary incontinence | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Cystitis noninfective | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Acute kidney injury | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Pelvic pain | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Pelvic pain | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 2/22 (9.1%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 2/19 (10.5%) | 2 | 2/22 (9.1%) | 2 | 2/22 (9.1%) | 3 |
| Dysphonia | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Dyspnoea | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Dyspnoea exertional | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Epistaxis | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Haemoptysis | 1/19 (5.3%) | 2 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Pulmonary embolism | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Rhinorrhoea | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Oropharyngeal discomfort | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Oropharyngeal pain | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 3/22 (13.6%) | 3 |
| Upper-airway cough syndrome | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Cough | 2/19 (10.5%) | 2 | 3/22 (13.6%) | 3 | 3/22 (13.6%) | 5 |
| Dyspnoea exertional | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Haemoptysis | 1/19 (5.3%) | 2 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Pulmonary embolism | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Oropharyngeal pain | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 4/22 (18.2%) | 4 |
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Dry skin | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 1/22 (4.5%) | 1 |
| Erythema multiforme | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Hyperkeratosis | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Night sweats | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Pruritus | 0/19 (0%) | 0 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Rash | 1/19 (5.3%) | 1 | 1/22 (4.5%) | 2 | 2/22 (9.1%) | 2 |
| Skin atrophy | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Skin discolouration | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Skin fissures | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Skin hyperpigmentation | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Night sweats | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Rash | 1/19 (5.3%) | 1 | 1/22 (4.5%) | 2 | 2/22 (9.1%) | 2 |
| Skin fissures | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 0/22 (0%) | 0 |
| Vascular disorders | ||||||
| Hypertension | 3/19 (15.8%) | 3 | 1/22 (4.5%) | 3 | 4/22 (18.2%) | 7 |
| Hypotension | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Systolic hypertension | 0/19 (0%) | 0 | 1/22 (4.5%) | 1 | 0/22 (0%) | 0 |
| Hot flush | 1/19 (5.3%) | 1 | 3/22 (13.6%) | 3 | 5/22 (22.7%) | 5 |
| Hypertension | 3/19 (15.8%) | 3 | 2/22 (9.1%) | 6 | 6/22 (27.3%) | 13 |
| Hypotension | 1/19 (5.3%) | 1 | 0/22 (0%) | 0 | 1/22 (4.5%) | 1 |
| Hot flush | 1/19 (5.3%) | 1 | 3/22 (13.6%) | 3 | 5/22 (22.7%) | 5 |
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 | (+)1-888-84 22937 |
| clinical-trials-contact@bayer.com |
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT02034552
Other Study ID Numbers:
- 16544
First Posted:
Jan 13, 2014
Last Update Posted:
Jul 23, 2019
Last Verified:
Jul 1, 2019