Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Compare the Safety and Efficacy of Romosozumab (AMG 785) Versus Placebo in Men With Osteoporosis (BRIDGE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02186171
Recruitment Status : Completed
First Posted : July 10, 2014
Results First Posted : May 28, 2019
Last Update Posted : May 28, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Osteoporosis in Men
Interventions Biological: Romosozumab
Drug: Placebo
Enrollment 245
Recruitment Details This study was conducted at 31 centers in Europe, North America, Latin America, and Japan. Participants were enrolled from 16 June 2014 to 27 January 2015.
Pre-assignment Details Participants were randomized in a 2:1 ratio to receive 210 mg romosozumab or matched placebo in a blinded fashion for the duration of the 12-month treatment period. Randomization was stratified by geographic region (Europe, North America, Latin America, and Japan).
Arm/Group Title Placebo Romosozumab 210 mg
Hide Arm/Group Description Participants received placebo subcutaneous injections once a month (QM) for 12 months. Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Period Title: Overall Study
Started 82 163
Received Treatment 81 163
Completed 78 148
Not Completed 4 15
Reason Not Completed
Withdrawal by Subject             1             9
Lost to Follow-up             2             2
Death             1             2
Protocol-specified Criteria             0             2
Arm/Group Title Placebo Romosozumab 210 mg Total
Hide Arm/Group Description Participants received placebo subcutaneous injections once a month (QM) for 12 months. Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months. Total of all reporting groups
Overall Number of Baseline Participants 82 163 245
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 82 participants 163 participants 245 participants
71.5  (6.9) 72.4  (7.4) 72.1  (7.3)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 82 participants 163 participants 245 participants
18 - 64 years
11
  13.4%
31
  19.0%
42
  17.1%
65 - 74 years
42
  51.2%
62
  38.0%
104
  42.4%
75 years and over
29
  35.4%
70
  42.9%
99
  40.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 82 participants 163 participants 245 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
82
 100.0%
163
 100.0%
245
 100.0%
Race  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 82 participants 163 participants 245 participants
White
60
  73.2%
120
  73.6%
180
  73.5%
Asian
9
  11.0%
18
  11.0%
27
  11.0%
Black or African American
0
   0.0%
1
   0.6%
1
   0.4%
Other
13
  15.9%
23
  14.1%
36
  14.7%
Multiple
0
   0.0%
1
   0.6%
1
   0.4%
Geographic Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 82 participants 163 participants 245 participants
Europe
54
  65.9%
108
  66.3%
162
  66.1%
Japan
9
  11.0%
18
  11.0%
27
  11.0%
Latin America
12
  14.6%
23
  14.1%
35
  14.3%
North America
7
   8.5%
14
   8.6%
21
   8.6%
Lumbar Spine Bone Mineral Density T-score   [1] 
Mean (Standard Deviation)
Unit of measure:  T-score
Number Analyzed 82 participants 163 participants 245 participants
-2.33  (1.41) -2.22  (1.19) -2.26  (1.27)
[1]
Measure Description: The T-score is the bone mineral density (BMD) at the site when compared to that of a healthy thirty-year-old. Normal is a T-score of −1.0 or higher; Osteopenia is defined as between −1.0 and −2.5; Osteoporosis is defined as −2.5 or lower, meaning a bone density that is two and a half standard deviations below the mean of a thirty-year-old man/woman.
Total Hip BMD T-score  
Mean (Standard Deviation)
Unit of measure:  T-score
Number Analyzed 82 participants 163 participants 245 participants
-1.92  (0.65) -1.92  (0.59) -1.92  (0.61)
Femoral Neck BMD T-score  
Mean (Standard Deviation)
Unit of measure:  T-score
Number Analyzed 82 participants 163 participants 245 participants
-2.30  (0.52) -2.34  (0.52) -2.33  (0.52)
1.Primary Outcome
Title Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Month 12
Hide Description Lumbar spine bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time Frame Baseline and month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Primary efficacy analysis subset, which includes all randomized participants who had a baseline DXA BMD measurement and at least 1 post-baseline DXA BMD measurement at the lumbar spine; last observation carried forward (LOCF) imputation was used.
Arm/Group Title Placebo Romosozumab 210 mg
Hide Arm/Group Description:
Participants received placebo subcutaneous injections once a month (QM) for 12 months.
Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Overall Number of Participants Analyzed 79 157
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.2  (0.5) 12.1  (0.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 210 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model adjusting for treatment, baseline BMD value, machine type, machine type-by-baseline BMD value, baseline testosterone level, geographic region, and using a variance structure allowing for heterogeneity between treatment groups.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 10.9
Confidence Interval (2-Sided) 95%
9.6 to 12.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.6
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percent Change From Baseline in BMD at the Total Hip at Month 12
Hide Description Total hip bone mineral density was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time Frame Baseline and month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Primary efficacy analysis subset, which includes all randomized participants who had a baseline DXA BMD measurement and at least 1 post-baseline DXA BMD measurement at the total hip; LOCF imputation was used.
Arm/Group Title Placebo Romosozumab 210 mg
Hide Arm/Group Description:
Participants received placebo subcutaneous injections once a month (QM) for 12 months.
Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Overall Number of Participants Analyzed 79 158
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.5  (0.3) 2.5  (0.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 210 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The Hochberg procedure was employed to control the overall type 1 error for the percent change from baseline at 12 months in total hip and femoral neck to maintain the overall significance level at 0.05.
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model adjusting for treatment, baseline BMD value, machine type, machine type-by-baseline BMD value, baseline testosterone level, geographic region, and using a variance structure allowing for heterogeneity between treatment groups.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.0
Confidence Interval (2-Sided) 95%
2.3 to 3.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.4
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change From Baseline in BMD at the Femoral Neck at Month 12
Hide Description Femoral neck bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time Frame Baseline and month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Primary efficacy analysis subset, which includes all randomized participants who had a baseline DXA BMD measurement and at least 1 post-baseline DXA BMD measurement at the femoral neck; LOCF imputation was used.
Arm/Group Title Placebo Romosozumab 210 mg
Hide Arm/Group Description:
Participants received placebo subcutaneous injections once a month (QM) for 12 months.
Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Overall Number of Participants Analyzed 79 158
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.2  (0.4) 2.2  (0.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 210 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The Hochberg procedure was employed to control the overall type 1 error for the percent change from baseline at 12 months in total hip and femoral neck to maintain the overall significance level at 0.05.
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model adjusting for treatment, baseline BMD value, machine type, machine type-by-baseline BMD value, baseline testosterone level, geographic region, and using a variance structure allowing for heterogeneity between treatment groups.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.4
Confidence Interval (2-Sided) 95%
1.5 to 3.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.5
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline in Lumbar Spine BMD at Month 6
Hide Description Lumbar spine bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time Frame Baseline and month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Primary efficacy analysis subset with available data at baseline and month 6.
Arm/Group Title Placebo Romosozumab 210 mg
Hide Arm/Group Description:
Participants received placebo subcutaneous injections once a month (QM) for 12 months.
Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Overall Number of Participants Analyzed 78 156
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.3  (0.4) 9.0  (0.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 210 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The Hochberg procedure was employed to control the overall type 1 error for the percent change from baseline at 6 months at the lumbar spine, total hip and femoral neck BMD in order to maintain the overall significance level at 0.05.
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model adjusting for treatment, baseline BMD value, machine type, machine type-by-baseline BMD value, baseline testosterone level, geographic region, and using a variance structure allowing for heterogeneity between treatment groups.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 8.7
Confidence Interval (2-Sided) 95%
7.6 to 9.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.5
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percent Change From Baseline in BMD at the Total Hip at Month 6
Hide Description Bone mineral density was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time Frame Baseline and month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Primary efficacy analysis subset with available data at baseline and month 6.
Arm/Group Title Placebo Romosozumab 210 mg
Hide Arm/Group Description:
Participants received placebo subcutaneous injections once a month (QM) for 12 months.
Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Overall Number of Participants Analyzed 78 157
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.2  (0.2) 1.6  (0.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 210 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The Hochberg procedure was employed to control the overall type 1 error for the percent change from baseline at 6 months at the lumbar spine, total hip and femoral neck BMD in order to maintain the overall significance level at 0.05.
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model adjusting for treatment, baseline BMD value, machine type, machine type-by-baseline BMD value, baseline testosterone level, geographic region, and using a variance structure allowing for heterogeneity between treatment groups.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
0.8 to 2.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.3
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percent Change From Baseline in BMD at the Femoral Neck at Month 6
Hide Description Bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time Frame Baseline and month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Primary efficacy analysis subset with available data at baseline and month 6.
Arm/Group Title Placebo Romosozumab 210 mg
Hide Arm/Group Description:
Participants received placebo subcutaneous injections once a month (QM) for 12 months.
Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Overall Number of Participants Analyzed 78 157
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.0  (0.4) 1.2  (0.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 210 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The Hochberg procedure was employed to control the overall type 1 error for the percent change from baseline at 6 months at the lumbar spine, total hip and femoral neck BMD in order to maintain the overall significance level at 0.05.
Statistical Test of Hypothesis P-Value = 0.0033
Comments ANCOVA model adjusting for treatment, baseline BMD value, machine type, machine type-by-baseline BMD value, baseline testosterone level, geographic region, and using a variance structure allowing for heterogeneity between treatment groups.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
0.4 to 2.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.4
Estimation Comments [Not Specified]
Time Frame 15 months
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Placebo Romosozumab 210 mg
Hide Arm/Group Description Participants received placebo subcutaneous injections once a month (QM) for 12 months. Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
All-Cause Mortality
Placebo Romosozumab 210 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Placebo Romosozumab 210 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   10/81 (12.35%)   23/163 (14.11%) 
Cardiac disorders     
Angina unstable  1  0/81 (0.00%)  1/163 (0.61%) 
Atrial fibrillation  1  1/81 (1.23%)  0/163 (0.00%) 
Atrial flutter  1  1/81 (1.23%)  1/163 (0.61%) 
Cardiac failure  1  0/81 (0.00%)  1/163 (0.61%) 
Cardiac valve disease  1  1/81 (1.23%)  0/163 (0.00%) 
Cardio-respiratory arrest  1  0/81 (0.00%)  1/163 (0.61%) 
Coronary artery stenosis  1  0/81 (0.00%)  1/163 (0.61%) 
Myocardial ischaemia  1  0/81 (0.00%)  2/163 (1.23%) 
Wolff-Parkinson-White syndrome  1  0/81 (0.00%)  1/163 (0.61%) 
Gastrointestinal disorders     
Abdominal pain  1  1/81 (1.23%)  0/163 (0.00%) 
Abdominal pain upper  1  1/81 (1.23%)  0/163 (0.00%) 
Gastrooesophageal reflux disease  1  0/81 (0.00%)  1/163 (0.61%) 
Intra-abdominal haemorrhage  1  1/81 (1.23%)  0/163 (0.00%) 
General disorders     
Death  1  1/81 (1.23%)  1/163 (0.61%) 
Implant site haematoma  1  0/81 (0.00%)  1/163 (0.61%) 
Non-cardiac chest pain  1  1/81 (1.23%)  1/163 (0.61%) 
Hepatobiliary disorders     
Cholecystitis  1  0/81 (0.00%)  1/163 (0.61%) 
Infections and infestations     
Appendicitis  1  0/81 (0.00%)  1/163 (0.61%) 
Appendicitis perforated  1  0/81 (0.00%)  1/163 (0.61%) 
Atypical pneumonia  1  1/81 (1.23%)  0/163 (0.00%) 
Device related infection  1  0/81 (0.00%)  1/163 (0.61%) 
Escherichia sepsis  1  0/81 (0.00%)  1/163 (0.61%) 
Pneumonia  1  0/81 (0.00%)  2/163 (1.23%) 
Pneumonia bacterial  1  1/81 (1.23%)  0/163 (0.00%) 
Urinary tract infection  1  0/81 (0.00%)  1/163 (0.61%) 
Injury, poisoning and procedural complications     
Anaemia postoperative  1  0/81 (0.00%)  1/163 (0.61%) 
Femur fracture  1  1/81 (1.23%)  0/163 (0.00%) 
Humerus fracture  1  1/81 (1.23%)  0/163 (0.00%) 
Laceration  1  0/81 (0.00%)  1/163 (0.61%) 
Rib fracture  1  0/81 (0.00%)  1/163 (0.61%) 
Subdural haematoma  1  0/81 (0.00%)  1/163 (0.61%) 
Thoracic vertebral fracture  1  0/81 (0.00%)  1/163 (0.61%) 
Upper limb fracture  1  1/81 (1.23%)  0/163 (0.00%) 
Musculoskeletal and connective tissue disorders     
Osteoarthritis  1  0/81 (0.00%)  1/163 (0.61%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  0/81 (0.00%)  1/163 (0.61%) 
Oropharyngeal cancer  1  0/81 (0.00%)  1/163 (0.61%) 
Nervous system disorders     
Carotid arteriosclerosis  1  0/81 (0.00%)  1/163 (0.61%) 
Carotid artery stenosis  1  0/81 (0.00%)  1/163 (0.61%) 
Cerebral ischaemia  1  0/81 (0.00%)  1/163 (0.61%) 
Cerebrovascular accident  1  0/81 (0.00%)  1/163 (0.61%) 
Dementia Alzheimer's type  1  1/81 (1.23%)  0/163 (0.00%) 
Epilepsy  1  1/81 (1.23%)  0/163 (0.00%) 
Haemorrhagic stroke  1  0/81 (0.00%)  1/163 (0.61%) 
Lacunar infarction  1  1/81 (1.23%)  0/163 (0.00%) 
Syncope  1  1/81 (1.23%)  0/163 (0.00%) 
Vascular encephalopathy  1  0/81 (0.00%)  1/163 (0.61%) 
Psychiatric disorders     
Depressed mood  1  0/81 (0.00%)  1/163 (0.61%) 
Depression  1  0/81 (0.00%)  1/163 (0.61%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/81 (0.00%)  1/163 (0.61%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  1/81 (1.23%)  0/163 (0.00%) 
Emphysema  1  1/81 (1.23%)  0/163 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Romosozumab 210 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   41/81 (50.62%)   74/163 (45.40%) 
Gastrointestinal disorders     
Constipation  1  1/81 (1.23%)  9/163 (5.52%) 
Infections and infestations     
Nasopharyngitis  1  22/81 (27.16%)  35/163 (21.47%) 
Injury, poisoning and procedural complications     
Procedural pain  1  6/81 (7.41%)  8/163 (4.91%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  8/81 (9.88%)  10/163 (6.13%) 
Back pain  1  4/81 (4.94%)  15/163 (9.20%) 
Muscle spasms  1  5/81 (6.17%)  3/163 (1.84%) 
Myalgia  1  5/81 (6.17%)  4/163 (2.45%) 
Nervous system disorders     
Headache  1  6/81 (7.41%)  10/163 (6.13%) 
Vascular disorders     
Hypertension  1  5/81 (6.17%)  14/163 (8.59%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
EMail: medinfo@amgen.com
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02186171    
Other Study ID Numbers: 20110174
2013-005551-32 ( EudraCT Number )
First Submitted: June 23, 2014
First Posted: July 10, 2014
Results First Submitted: May 3, 2019
Results First Posted: May 28, 2019
Last Update Posted: May 28, 2019