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A Randomized, Double-Blind Study to Compare the Efficacy of Treatment With Denosumab Versus Alendronate Sodium in Postmenopausal Women With Low Bone Mineral Density.

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: NCT00330460
Recruitment Status : Completed
First Posted : May 26, 2006
Results First Posted : July 19, 2010
Last Update Posted : January 24, 2011
Sponsor:
Information provided by:
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Osteoporosis
Osteopenia
Interventions Drug: Alendronate
Drug: Denosumab
Enrollment 1189
Recruitment Details First Subject Enrolled: 26-Apr-2006 Last Subject Enrolled: 17-Nov-2006
Pre-assignment Details  
Arm/Group Title Alendronate 70 mg QW Denosumab 60 mg Q6M
Hide Arm/Group Description [Not Specified] [Not Specified]
Period Title: Overall Study
Started 595 594
Completed 553 561
Not Completed 42 33
Reason Not Completed
Physician Decision             1             0
Adverse Event             10             8
Withdrawal by Subject             18             17
Death             1             1
Ineligibility determined             1             3
Lost to Follow-up             8             3
Noncompliance             2             1
Other             1             0
Arm/Group Title Alendronate 70 mg QW Denosumab 60 mg Q6M Total
Hide Arm/Group Description [Not Specified] [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 595 594 1189
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 595 participants 594 participants 1189 participants
64.6  (8.3) 64.1  (8.6) 64.4  (8.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 595 participants 594 participants 1189 participants
Female
595
 100.0%
594
 100.0%
1189
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 595 participants 594 participants 1189 participants
White or Caucasian 502 502 1004
Black or African American 9 7 16
Hispanic or Latino 69 66 135
Asian 8 6 14
Japanese 4 3 7
American Indian or Alaska Native 0 2 2
Native Hawaiian or Other Pacific Islander 0 1 1
Other 3 7 10
1.Primary Outcome
Title Total Hip Bone Mineral Density Percent Change From Baseline at Month 12
Hide Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who have a nonmissing baseline and at least 1 nonmissing postbaseline evaluation at or prior to month 12. LOCF used as imputation method.
Arm/Group Title Alendronate 70 mg QW Denosumab 60 mg Q6M
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 572 579
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent Change from Baseline
2.6
(2.4 to 2.8)
3.5
(3.3 to 3.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alendronate 70 mg QW, Denosumab 60 mg Q6M
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority margin = -1.22%.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1
Confidence Interval 95%
0.7 to 1.2
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12
Hide Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alendronate 70 mg QW Denosumab 60 mg Q6M
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 571 579
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent Change from Baseline
4.2
(3.9 to 4.5)
5.3
(5.0 to 5.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alendronate 70 mg QW, Denosumab 60 mg Q6M
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority margin = -2.29%.
Statistical Test of Hypothesis P-Value <0.0001
Comments The reported p-value was the one-sided adjusted p-valued based on multiplicity adjustment of the secondary efficacy endpoints
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.1
Confidence Interval 95%
0.7 to 1.4
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Trochanter Bone Mineral Density Percent Change From Baseline at Month 12
Hide Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alendronate 70 mg QW Denosumab 60 mg Q6M
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 572 579
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent Change from Baseline
3.4
(3.1 to 3.7)
4.5
(4.1 to 4.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alendronate 70 mg QW, Denosumab 60 mg Q6M
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority margin = -1.65%
Statistical Test of Hypothesis P-Value <0.0001
Comments The reported p-value was the one-sided adjusted p-valued based on multiplicity adjustment of the secondary efficacy endpoints
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1
Confidence Interval 95%
0.6 to 1.4
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 12
Hide Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alendronate 70 mg QW Denosumab 60 mg Q6M
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 572 579
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent Change from Baseline
1.8
(1.5 to 2.1)
2.4
(2.2 to 2.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alendronate 70 mg QW, Denosumab 60 mg Q6M
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority margin = -1.04%
Statistical Test of Hypothesis P-Value <0.0001
Comments The reported p-value was the one-sided adjusted p-valued based on multiplicity adjustment of the secondary efficacy endpoints
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.6
Confidence Interval 95%
0.3 to 1
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12
Hide Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alendronate 70 mg QW Denosumab 60 mg Q6M
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 569 573
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent Change from Baseline
0.6
(0.3 to 0.8)
1.1
(0.9 to 1.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alendronate 70 mg QW, Denosumab 60 mg Q6M
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments The reported p-value was the one-sided adjusted p-valued based on multiplicity adjustment of the secondary efficacy endpoints
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.6
Confidence Interval 95%
0.3 to 0.9
Estimation Comments [Not Specified]
Time Frame 12 months
Adverse Event Reporting Description The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
 
Arm/Group Title Alendronate 70 mg QW Denosumab 60 mg Q6M
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
Alendronate 70 mg QW Denosumab 60 mg Q6M
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Alendronate 70 mg QW Denosumab 60 mg Q6M
Affected / at Risk (%) Affected / at Risk (%)
Total   37/586 (6.31%)   34/593 (5.73%) 
Cardiac disorders     
Acute coronary syndrome  1  1/586 (0.17%)  0/593 (0.00%) 
Atrial fibrillation  1  0/586 (0.00%)  1/593 (0.17%) 
Bradycardia  1  1/586 (0.17%)  0/593 (0.00%) 
Cardio-respiratory arrest  1  0/586 (0.00%)  1/593 (0.17%) 
Congestive cardiomyopathy  1  1/586 (0.17%)  0/593 (0.00%) 
Coronary artery disease  1  1/586 (0.17%)  1/593 (0.17%) 
Coronary artery stenosis  1  1/586 (0.17%)  0/593 (0.00%) 
Ventricular asystole  1  0/586 (0.00%)  1/593 (0.17%) 
Eye disorders     
Macular hole  1  1/586 (0.17%)  0/593 (0.00%) 
Retinal tear  1  0/586 (0.00%)  1/593 (0.17%) 
Gastrointestinal disorders     
Abdominal hernia  1  0/586 (0.00%)  1/593 (0.17%) 
Colitis ischaemic  1  0/586 (0.00%)  1/593 (0.17%) 
Gastric ulcer perforation  1  0/586 (0.00%)  1/593 (0.17%) 
Gastrointestinal haemorrhage  1  0/586 (0.00%)  1/593 (0.17%) 
Inguinal hernia  1  0/586 (0.00%)  1/593 (0.17%) 
Intestinal obstruction  1  1/586 (0.17%)  0/593 (0.00%) 
Periodontitis  1  1/586 (0.17%)  0/593 (0.00%) 
Small intestinal obstruction  1  1/586 (0.17%)  1/593 (0.17%) 
General disorders     
Chest pain  1  1/586 (0.17%)  0/593 (0.00%) 
Non-cardiac chest pain  1  2/586 (0.34%)  1/593 (0.17%) 
Hepatobiliary disorders     
Cholelithiasis  1  0/586 (0.00%)  1/593 (0.17%) 
Infections and infestations     
Abscess limb  1  1/586 (0.17%)  0/593 (0.00%) 
Diverticulitis  1  0/586 (0.00%)  3/593 (0.51%) 
Ear infection  1  0/586 (0.00%)  1/593 (0.17%) 
Infected cyst  1  1/586 (0.17%)  0/593 (0.00%) 
Localised infection  1  0/586 (0.00%)  1/593 (0.17%) 
Pneumonia  1  3/586 (0.51%)  1/593 (0.17%) 
Pseudomembranous colitis  1  0/586 (0.00%)  1/593 (0.17%) 
Pyelonephritis  1  0/586 (0.00%)  1/593 (0.17%) 
Sepsis  1  0/586 (0.00%)  1/593 (0.17%) 
Upper respiratory tract infection  1  1/586 (0.17%)  0/593 (0.00%) 
Urosepsis  1  0/586 (0.00%)  1/593 (0.17%) 
Injury, poisoning and procedural complications     
Facial bones fracture  1  1/586 (0.17%)  0/593 (0.00%) 
Fibula fracture  1  1/586 (0.17%)  1/593 (0.17%) 
Humerus fracture  1  0/586 (0.00%)  1/593 (0.17%) 
Lumbar vertebral fracture  1  1/586 (0.17%)  0/593 (0.00%) 
Pelvic fracture  1  1/586 (0.17%)  0/593 (0.00%) 
Tibia fracture  1  2/586 (0.34%)  1/593 (0.17%) 
Wrist fracture  1  1/586 (0.17%)  0/593 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/586 (0.17%)  0/593 (0.00%) 
Chondromalacia  1  0/586 (0.00%)  1/593 (0.17%) 
Osteoarthritis  1  0/586 (0.00%)  1/593 (0.17%) 
Rotator cuff syndrome  1  1/586 (0.17%)  0/593 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign breast neoplasm  1  0/586 (0.00%)  1/593 (0.17%) 
Breast cancer  1  1/586 (0.17%)  2/593 (0.34%) 
Cholesteatoma  1  0/586 (0.00%)  1/593 (0.17%) 
Fibroma  1  1/586 (0.17%)  0/593 (0.00%) 
Gastric cancer  1  0/586 (0.00%)  1/593 (0.17%) 
Metastases to liver  1  0/586 (0.00%)  1/593 (0.17%) 
Metastatic neoplasm  1  1/586 (0.17%)  0/593 (0.00%) 
Mycosis fungoides  1  0/586 (0.00%)  1/593 (0.17%) 
Ovarian cancer recurrent  1  1/586 (0.17%)  0/593 (0.00%) 
Renal cell carcinoma stage unspecified  1  0/586 (0.00%)  1/593 (0.17%) 
Small cell lung cancer metastatic  1  1/586 (0.17%)  0/593 (0.00%) 
Squamous cell carcinoma  1  0/586 (0.00%)  1/593 (0.17%) 
Vaginal cancer  1  1/586 (0.17%)  0/593 (0.00%) 
Nervous system disorders     
Carotid artery stenosis  1  0/586 (0.00%)  1/593 (0.17%) 
Cerebral ischaemia  1  0/586 (0.00%)  1/593 (0.17%) 
Cerebrovascular accident  1  1/586 (0.17%)  0/593 (0.00%) 
Convulsion  1  1/586 (0.17%)  0/593 (0.00%) 
Dizziness  1  0/586 (0.00%)  1/593 (0.17%) 
Hypoglycaemic coma  1  1/586 (0.17%)  0/593 (0.00%) 
Migraine  1  1/586 (0.17%)  0/593 (0.00%) 
Transient ischaemic attack  1  2/586 (0.34%)  0/593 (0.00%) 
Psychiatric disorders     
Alcoholism  1  0/586 (0.00%)  1/593 (0.17%) 
Anxiety  1  1/586 (0.17%)  0/593 (0.00%) 
Depression  1  1/586 (0.17%)  1/593 (0.17%) 
Renal and urinary disorders     
Nephrolithiasis  1  1/586 (0.17%)  0/593 (0.00%) 
Renal failure  1  1/586 (0.17%)  0/593 (0.00%) 
Reproductive system and breast disorders     
Ovarian cyst  1  0/586 (0.00%)  1/593 (0.17%) 
Pelvic pain  1  1/586 (0.17%)  0/593 (0.00%) 
Pelvic peritoneal adhesions  1  1/586 (0.17%)  0/593 (0.00%) 
Urogenital prolapse  1  1/586 (0.17%)  0/593 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  0/586 (0.00%)  1/593 (0.17%) 
Social circumstances     
Activities of daily living impaired  1  0/586 (0.00%)  1/593 (0.17%) 
Vascular disorders     
Aortic stenosis  1  1/586 (0.17%)  0/593 (0.00%) 
Arteriosclerosis  1  0/586 (0.00%)  1/593 (0.17%) 
Deep vein thrombosis  1  1/586 (0.17%)  0/593 (0.00%) 
Hypertension  1  1/586 (0.17%)  0/593 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alendronate 70 mg QW Denosumab 60 mg Q6M
Affected / at Risk (%) Affected / at Risk (%)
Total   261/586 (44.54%)   270/593 (45.53%) 
Gastrointestinal disorders     
Constipation  1  31/586 (5.29%)  36/593 (6.07%) 
Diarrhoea  1  20/586 (3.41%)  30/593 (5.06%) 
Dyspepsia  1  29/586 (4.95%)  34/593 (5.73%) 
Infections and infestations     
Influenza  1  42/586 (7.17%)  41/593 (6.91%) 
Nasopharyngitis  1  43/586 (7.34%)  45/593 (7.59%) 
Upper respiratory tract infection  1  25/586 (4.27%)  36/593 (6.07%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  56/586 (9.56%)  75/593 (12.65%) 
Back pain  1  56/586 (9.56%)  42/593 (7.08%) 
Pain in extremity  1  37/586 (6.31%)  31/593 (5.23%) 
Nervous system disorders     
Headache  1  32/586 (5.46%)  30/593 (5.06%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
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 multi-center 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
Layout table for additonal information
Responsible Party: Global Development Leader, Amgen Inc.
ClinicalTrials.gov Identifier: NCT00330460    
Other Study ID Numbers: 20050141
First Submitted: April 6, 2006
First Posted: May 26, 2006
Results First Submitted: June 18, 2010
Results First Posted: July 19, 2010
Last Update Posted: January 24, 2011