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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-001821-28 | EudraCT Number |
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This study will compare the effectiveness of denosumab treatment every 6 months with once yearly zoledronic acid treatment on bone mineral density (BMD) at various skeletal sites.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Denosumab 60 mg | Experimental | Participants received denosumab 60 mg subcutaneous injection once every 6 months for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1. |
|
| Zoledronic Acid 5 mg | Active Comparator | Participants received zoledronic acid 5 mg by intravenous infusion on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Denosumab | Biological | Denosumab 60 mg administered by subcutaneous injection once every 6 months. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis | Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging facility. | Baseline and Month 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis | BMD of the hip was measured by DXA. DXA scans were analyzed by a central imaging facility. | Baseline and Month 12 |
| Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Received other osteoporosis treatment or bone active treatment
Evidence of history of any of the following:
Abnormalities of the following per central laboratory reference ranges:
History of any solid organ or bone marrow transplant
Malignancy (except nonmelanoma skin cancers, cervical or breast ductal carcinoma in situ) within the last 5 years
Known intolerance to calcium or vitamin D supplements
Self-reported alcohol or drug abuse within 12 months prior to screening
Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s)
History or evidence of any other clinically significant disorder, condition or disease that in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Santa Monica | California | 90404 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27270237 | Background | Miller PD, Pannacciulli N, Brown JP, Czerwinski E, Nedergaard BS, Bolognese MA, Malouf J, Bone HG, Reginster JY, Singer A, Wang C, Wagman RB, Cummings SR. Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates. J Clin Endocrinol Metab. 2016 Aug;101(8):3163-70. doi: 10.1210/jc.2016-1801. Epub 2016 Jun 6. | |
| 31776637 |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
Not provided
Participants were randomized in a 1:1 allocation ratio to receive either denosumab or zoledronic acid. Randomization was stratified by screening serum type I collagen C-telopeptide (sCTX) values (< 0.3 ng/mL, 0.3 to 0.5 ng/mL).
This study was conducted at 37 centers in Belgium, Denmark, Poland, Spain, Canada, United States of America, and Australia. The first participant enrolled on 07 November 2012 and the last participant enrolled on 15 January 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | Zoledronic Acid 5 mg Q12M | Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6. |
| FG001 | Denosumab 60 mg Q6M |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Zoledronic Acid | Drug | Zoledronic acid 5 mg administered by intravenous infusion once a year |
|
|
| Placebo to Denosumab | Drug | Administered by subcutaneous injection once every 6 months |
|
| Placebo to Zoledronic Acid | Drug | Administered by intravenous infusion once a year |
|
| Baseline and Month 12 |
| Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis | Baseline and Month 12 |
| Lakewood |
| Colorado |
| 80227 |
| United States |
| Research Site | Longmont | Colorado | 80501 | United States |
| Research Site | Washington D.C. | District of Columbia | 20007 | United States |
| Research Site | Bethesda | Maryland | 20817 | United States |
| Research Site | Hagerstown | Maryland | 21740 | United States |
| Research Site | Detroit | Michigan | 48236 | United States |
| Research Site | West Haverstraw | New York | 10993 | United States |
| Research Site | Houston | Texas | 77074 | United States |
| Research Site | Maroubra | New South Wales | 2035 | Australia |
| Research Site | Penrith | New South Wales | 2750 | Australia |
| Research Site | St Leonards | New South Wales | 2065 | Australia |
| Research Site | Box Hill | Victoria | 3128 | Australia |
| Research Site | Geelong | Victoria | 3220 | Australia |
| Research Site | Parkville | Victoria | 3050 | Australia |
| Research Site | Brussels | 1000 | Belgium |
| Research Site | Brussels | 1020 | Belgium |
| Research Site | Brussels | 1050 | Belgium |
| Research Site | Brussels | 1090 | Belgium |
| Research Site | Genk | 3600 | Belgium |
| Research Site | Leuven | 3000 | Belgium |
| Research Site | Liège | 4020 | Belgium |
| Research Site | Merksem | 2170 | Belgium |
| Research Site | Tessenderlo | 3980 | Belgium |
| Research Site | Wilrijk | 2610 | Belgium |
| Research Site | Yvoir | 5530 | Belgium |
| Research Site | Calgary | Alberta | T2N 4Z6 | Canada |
| Research Site | Vancouver | British Columbia | V5Z 4E1 | Canada |
| Research Site | Halifax | Nova Scotia | B3H 2Y9 | Canada |
| Research Site | Toronto | Ontario | M5C 2T2 | Canada |
| Research Site | Toronto | Ontario | M5G 2C4 | Canada |
| Research Site | Toronto | Ontario | M9W 4L6 | Canada |
| Research Site | Québec | Quebec | G1V 3M7 | Canada |
| Research Site | Aalborg | 9000 | Denmark |
| Research Site | Ballerup Municipality | 2750 | Denmark |
| Research Site | Vejle | 7100 | Denmark |
| Research Site | Bialystok | 15-879 | Poland |
| Research Site | Krakow | 31-501 | Poland |
| Research Site | Torun | 87-100 | Poland |
| Research Site | Warsaw | 01-192 | Poland |
| Research Site | Granada | Andalusia | 18012 | Spain |
| Research Site | Barcelona | Catalonia | 08036 | Spain |
| Research Site | Barcelona | Catalonia | 08041 | Spain |
| Research Site | Madrid | 28009 | Spain |
| Research Site | Madrid | 28040 | Spain |
| Miller PD, Pannacciulli N, Malouf-Sierra J, Singer A, Czerwinski E, Bone HG, Wang C, Huang S, Chines A, Lems W, Brown JP. Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates. Osteoporos Int. 2020 Jan;31(1):181-191. doi: 10.1007/s00198-019-05233-x. Epub 2019 Nov 28. |
| 31999376 | Background | Chotiyarnwong P, McCloskey E, Eastell R, McClung MR, Gielen E, Gostage J, McDermott M, Chines A, Huang S, Cummings SR. A Pooled Analysis of Fall Incidence From Placebo-Controlled Trials of Denosumab. J Bone Miner Res. 2020 Jun;35(6):1014-1021. doi: 10.1002/jbmr.3972. Epub 2020 Apr 2. |
Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1. |
| Received Study Treatment |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Zoledronic Acid 5 mg Q12M | Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6. |
| BG001 | Denosumab 60 mg Q6M | Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| ||||||||||||||||
| Screening serum CTX | Number | participants |
| ||||||||||||||||
| Lumbar Spine Bone Mineral Density (BMD) T-score | BMD was measured using dual-energy x-ray absorptiometry (DXA) of the lumbar spine. The T-score is a comparison of a person's bone density with that of a healthy 30-year-old of the same sex. Lower scores (more negative) mean lower bone density: A T-score of -2.5 or lower qualifies as osteoporosis and a T-score of -1.0 to -2.5 signifies osteopenia, meaning below-normal bone density without full osteoporosis. | Mean | Standard Deviation | T-score |
| ||||||||||||||
| Total Hip BMD T-score | Mean | Standard Deviation | T-score |
| |||||||||||||||
| Femoral Neck BMD T-score | Mean | Standard Deviation | T-score |
| |||||||||||||||
| Prior Oral Bisphosphonate Duration | Mean | Standard Deviation | years |
| |||||||||||||||
| Historical Fractures | An osteoporotic fracture is defined as a reported fracture excluding skull fracture, facial bones fracture, fingers fracture and toes fracture, fractures with high trauma severity, and pathological fractures. | Number | participants |
| |||||||||||||||
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m² |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis | Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging facility. | The primary efficacy analysis set includes all randomized participants who have a baseline BMD measurement and at least one postbaseline BMD measurement. Any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, last observation carried forward [LOCF]). | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline and Month 12 |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis | BMD of the hip was measured by DXA. DXA scans were analyzed by a central imaging facility. | The primary efficacy analysis set; any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, LOCF). | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline and Month 12 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis | The primary efficacy analysis set; any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, LOCF). | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline and Month 12 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis | The primary efficacy analysis set; any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, LOCF). | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline and Month 12 |
|
|
12 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Zoledronic Acid 5 mg Q12M | Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6. | 29 | 320 | 22 | 320 | ||
| EG001 | Denosumab 60 mg Q6M | Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1. | 25 | 320 | 15 | 320 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Atrial flutter | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Goitre | Endocrine disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Diverticulum | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Gastrointestinal obstruction | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Drug interaction | General disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Autoimmune hepatitis | Hepatobiliary disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Vulval abscess | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Concussion | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
| |
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
| |
| Tendon rupture | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Intervertebral disc disorder | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
| |
| Breast cancer female | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
| |
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
| |
| Lung adenocarcinoma stage I | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
| |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
| |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
| |
| Non-small cell lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
| |
| Pituitary tumour benign | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
| |
| Pleomorphic adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
| |
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
| |
| Cerebral thrombosis | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Cystocele | Reproductive system and breast disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Rectocele | Reproductive system and breast disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Uterine prolapse | Reproductive system and breast disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Knee operation | Surgical and medical procedures | MedDRA 17.1 | Systematic Assessment |
| |
| Tendon operation | Surgical and medical procedures | MedDRA 17.1 | Systematic Assessment |
| |
| Varicose vein operation | Surgical and medical procedures | MedDRA 17.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Peripheral artery thrombosis | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Varicose vein | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 |
| ID | Term |
|---|---|
| D015663 | Osteoporosis, Postmenopausal |
| ID | Term |
|---|---|
| D010024 | Osteoporosis |
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069448 | Denosumab |
| D000077211 | Zoledronic Acid |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
|
| Asian |
|
| Other |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| Multiple |
|
| ≥ 0.3 ng/mL |
|
| Missing |
|
| Prior osteoporotic fracture |
|
The lower bound of the 2-sided 95% confidence interval (CI) of (denosumab - zoledronic acid) was compared with the non-inferiority margin of -0.46% for assessing non-inferiority. |
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