OsteoporosisNCT02520362
Denosumab Safety Assessment in Multiple Observational Databases
An observational study of Osteoporosis, run by Amgen.
Trial summary
This is a prospective open-cohort study with annual assessment and reporting of descriptive findings from 5 secondary data sources, US Medicare, Optum Research Database (formerly United HealthCare), Scandinavian national health registry databases, including data from Denmark, Sweden, and Norway. Read more about this study
- Who is it for?
- Ages 30 to 99 years
- Conditions the study is for
- Osteoporosis
- What is being tested?
- denosumab and bisphosphonate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 517,991 participants
- Where
- No sites listed yet
- Study dates
- 31 May 2010to 21 Jul 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The main and sub-study populations will be identified based on the following inclusion and exclusion criteria. Patients in Medicare and Optum Research Database (formerly United HealthCare), will need to have appropriate plan coverage to be included in any of the following populations. Appropriate plan coverage for the Optum Research Database (formerly United HealthCare) refers to both pharmacy and medical plan coverage. Appropriate plan coverage for the US Medicare database refers to enrollment in traditional fee-for-service Medicare (Medicare Parts A and B coverage and not in a Medicare Advantage plan), plus Part D. The requirement of 12-months of continuous enrollment is not relevant for Scandinavian national registries because all citizens are enrolled in the universal health coverage from birth to death unless they move out of the country.
Who may be able to join
- Men ≥ 65 years old in the Medicare database or ≥ 30 years old in andthe Optum Research Database (formerly United HealthCare)United Healthcare who receive at least one denosumab 60 mg injection will be included. All men need to be continuously enrolled for at least 12 months prior to start of follow-up. A diagnosis code of osteoporosis or osteoporotic fracture would not be required because it is known that male osteoporosis is under-diagnosed. The exclusion of patients with cancer or Paget disease (as described in the Exclusion Criteria Section) will ensure that patients treated with Prolia is for osteoporosis but not for other indications. The index date is defined as the date when a patient first satisfies all inclusion criteria.
Who cannot join
- Men with a diagnosis of malignancy (excluding non-melanoma skin cancer) or treatment with chemotherapy, hormonal therapy or radiation therapy for cancer up to 12 months before the index date will be excluded.
- Men with Paget's disease during the 12-month period prior to the index date will also be excluded.
- Inclusion criteria for Men and Women Who Receive Prolia With Glucocorticoid Exd Exposure • Men and women identified from Medicare or Optum Research Database who are ≥65 years old (or ≥30 years old in Optum) on or before receiving at least 1 denosumab 60 mg injection or fill after approval date of Prolia for treatment of glucocorticoid-induced osteoporosis (18 May 2018) will be included. This includes both new and prevalent users of denosumab. The index date is defined as the date of the first denosumab administration on or after the approval date fulfilling both the database specific age, 12-month enrollment criteria, and has received a 90-day average daily dose equivalent ≥7.5 mg of prednisone at any time during the previous 12 months.
- Exclusion Criteria for Men and Women Who Receive Prolia With Glucocorticoid Exposure
- Men and women with a diagnosis of malignancy (excluding non-melanoma skin cancer) or treatment with chemotherapy, hormonal therapy or radiation therapy for cancer up to 12 months before the index date will be excluded. Men and women with Paget's disease during the 12-month period prior to the index date will also be excluded. The exclusion of subjects with cancer or Paget's disease will ensure that subjects included in the substudy are receiving denosumab for the treatment of osteoporosis, and not for other indications.
About this study
Official title: Denosumab Global Safety Assessment Among Women With Postmenopausal Osteoporosis (PMO), Men With Osteoporosis, and Men and Women Who Receive Prolia With Glucocorticoid Exposure in Multiple Observational Databases
This is a prospective open-cohort study with annual assessment and reporting of descriptive findings from 5 secondary data sources, US Medicare, Optum Research Database (formerly United HealthCare), Scandinavian national health registry databases, including data from Denmark, Sweden, and Norway. The study period will include up to 10 years in each data system depending on data availability. Descriptive statistics will be used to characterize cohorts with respect to patient characteristics and utilization patterns. Person-year adjusted AESI incidence rates will be calculated among postmenopausal women, postmenopausal women with osteoporosis, and exposure cohorts with a final comparative safety analysis. Subsequent sub-studies using US data systems were added to describe men with osteoporosis treated with Prolia and men and women who receive Prolia with glucocorticoid exposure.
Read the detailed description
This is a prospective open-cohort study with annual assessment and reporting of descriptive findings from 5 secondary data sources, US Medicare,Optum Research Database (formerly United HealthCare), Scandinavian national health registry databases, including data from Denmark, Sweden, and Norway. The study period will include up to 10 years in each data system depending on data availability. Descriptive statistics will be used to characterize exposure cohorts with respect to patient characteristics, clinical features, and AESI risk factors. Person-year adjusted AESI incidence rates will be calculated among postmenopausal women, postmenopausal women with osteoporosis, and exposure cohorts. Exploratory analyses comparing incidence rates of AESI in women with PMO adjusting for potential confounders will also be conducted. Descriptive statistics will be used to characterize denosumab utilisation patterns in patients who receive denosumab for PMO and in subjects who receive Prolia therapy for unapproved indications. Subsequent substudies using US data systems were added to describe men with osteoporosis treated with Prolia and men and women who receive Prolia with glucocorticoid exposure.
- Conditions
- Osteoporosis
- Being tested
- denosumab, bisphosphonate
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
denosumabDrug
subcutaneous injection
bisphosphonateDrug
The assessment of bisphosphonates includes branded oral bisphosphonates (eg, alendronate [Fosamax®], risedronate [Actonel®], ibandronate [Boniva®/Bonviva®] oral); generic bisphosphonates, including alendronate, neridodronate, and olpadronate; intravenous bisphosphonates including ibandronate IV, and zoledronate [Reclast®/Aclasta®].
| Study group | Role | What they receive |
|---|---|---|
| Postmenopausal Women | Postmenopausal Women | |
| Women with post menopausal osteoporosis | Women with post menopausal osteoporosis Receives: Drug: denosumab; Drug: bisphosphonate | |
| Prolia for unapproved indications | Patients who receive Prolia for unapproved indications Receives: Drug: denosumab | |
| Men with osteoporosis | Men with osteoporosis treated with denosumab Receives: Drug: denosumab | |
| Men and women who receive Prolia with Glucocorticoid exposure | Drug: denosumab subcutaneous injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence rates of Adverse Events of Special Interest (AESI)
Incidence rates of AESI (per 100,000 Person-years) will be assessed in postmenopausal women with osteoporosis (PMO) and by exposure cohort (denosumab or bisphosphonates)
Measured: Up to 10 years
Characteristics and Adverse Events of Special Interest (AESI) risk factors
Describe characteristics, clinical features, and AESI risk factors in women with PMO exposed to denosumab, women with PMO exposed to bisphosphonates, and all women with PMO.
Measured: Up to 10 years
Compare the incidence of the Adverse Events of Special Interests
Compare the incidence of the AESI in women with PMO exposed to denosumab to that in women with PMO exposed to bisphosphonates.
Measured: Up to 10 years
Describe incidence rates of Adverse Events of Special Interest (AESI)
Describe incidence rates of AESI in postmenopausal women.
Measured: Up to 10 years
Describe denosumab utilization patterns
Describe denosumab utilization patterns in patients who receive denosumab therapy for treatment of PMO.
Measured: Up to 10 years
Describe Prolia utilization patterns
Describe Prolia utilization patterns in patients who receive Prolia therapy for unapproved indications (indication, dosage, frequency).
Measured: Up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2015 (estimated)
- Study start31 May 2010
- Primary completion21 Jul 2023
- Study completion21 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 517,991 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Aarhus University Hospital, Optum, Inc., University of Alabama at Birmingham
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02520362
- Sponsor's protocol ID
- 20090522
- Status last verified
- Oct 2024
- First submitted
- 7 May 2015
- Last updated
- 4 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Publications
Xue F, Ma H, Stehman-Breen C, Haller C, Katz L, Wagman RB, Critchlow CW; Denosumab Global Safety Assessment Team. Design and methods of a postmarketing pharmacoepidemiology study assessing long-term safety of Prolia(R) (denosumab) for the treatment of postmenopausal osteoporosis. Pharmacoepidemiol Drug Saf. 2013 Oct;22(10):1107-14. doi: 10.1002/pds.3477. Epub 2013 Jul 15.
PubMed 23857864
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Denosumab Global Safety Assessment Among Women With Postmenopausal Osteoporosis (PMO), Men With Osteoporosis, and Men and Women Who Receive Prolia With Glucocorticoid Exposure in Multiple Observational Databases
- ClinicalTrials.gov ID
- NCT02520362
- Acronym / sponsor ID
- 20090522
- Conditions
- Osteoporosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 517,991 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Collaborators
- Aarhus University Hospital, Optum, Inc., University of Alabama at Birmingham
- Study start
- 31 May 2010 (actual)
- Primary completion
- 21 Jul 2023 (actual)
- Study completion
- 21 Jul 2023 (actual)
- First posted
- 11 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective open-cohort study with annual assessment and reporting of descriptive findings from 5 secondary data sources, US Medicare, Optum Research Database (formerly United HealthCare), Scandinavian national health registry databases, including data from Denmark, Sweden, and Norway. The study period will include up to 10 years in each data system depending on data availability. Descriptive statistics will be used to characterize cohorts with respect to patient characteristics and utilization patterns. Person-year adjusted AESI incidence rates will be calculated among postmenopausal women, postmenopausal women with osteoporosis, and exposure cohorts with a final comparative safety analysis. Subsequent sub-studies using US data systems were added to describe men with osteoporosis treated with Prolia and men and women who receive Prolia with glucocorticoid exposure.
Detailed description
This is a prospective open-cohort study with annual assessment and reporting of descriptive findings from 5 secondary data sources, US Medicare,Optum Research Database (formerly United HealthCare), Scandinavian national health registry databases, including data from Denmark, Sweden, and Norway. The study period will include up to 10 years in each data system depending on data availability. Descriptive statistics will be used to characterize exposure cohorts with respect to patient characteristics, clinical features, and AESI risk factors. Person-year adjusted AESI incidence rates will be calculated among postmenopausal women, postmenopausal women with osteoporosis, and exposure cohorts. Exploratory analyses comparing incidence rates of AESI in women with PMO adjusting for potential confounders will also be conducted. Descriptive statistics will be used to characterize denosumab utilisation patterns in patients who receive denosumab for PMO and in subjects who receive Prolia therapy for unapproved indications. Subsequent substudies using US data systems were added to describe men with osteoporosis treated with Prolia and men and women who receive Prolia with glucocorticoid exposure.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Postmenopausal Women | – | –Postmenopausal Women |
| Women with post menopausal osteoporosis | – | Drug: denosumab, Drug: bisphosphonateWomen with post menopausal osteoporosis |
| Prolia for unapproved indications | – | Drug: denosumabPatients who receive Prolia for unapproved indications |
| Men with osteoporosis | – | Drug: denosumabMen with osteoporosis treated with denosumab |
| Men and women who receive Prolia with Glucocorticoid exposure | – | –Drug: denosumab subcutaneous injection |
Who may qualify
- Ages
- 30 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The main and sub-study populations will be identified based on the following inclusion and exclusion criteria. Patients in Medicare and Optum Research Database (formerly United HealthCare), will need to have appropriate plan coverage to be included in any of the following populations. Appropriate plan coverage for the Optum Research Database (formerly United HealthCare) refers to both pharmacy and medical plan coverage. Appropriate plan coverage for the US Medicare database refers to enrollment in traditional fee-for-service Medicare (Medicare Parts A and B coverage and not in a Medicare Advantage plan), plus Part D. The requirement of 12-months of continuous enrollment is not relevant for Scandinavian national registries because all citizens are enrolled in the universal health coverage from birth to death unless they move out of the country.
Key inclusion criteria (1 listed)
- Men ≥ 65 years old in the Medicare database or ≥ 30 years old in andthe Optum Research Database (formerly United HealthCare)United Healthcare who receive at least one denosumab 60 mg injection will be included. All men need to be continuously enrolled for at least 12 months prior to start of follow-up. A diagnosis code of osteoporosis or osteoporotic fracture would not be required because it is known that male osteoporosis is under-diagnosed. The exclusion of patients with cancer or Paget disease (as described in the Exclusion Criteria Section) will ensure that patients treated with Prolia is for osteoporosis but not for other indications. The index date is defined as the date when a patient first satisfies all inclusion criteria.
Key exclusion criteria (5 listed)
- Men with a diagnosis of malignancy (excluding non-melanoma skin cancer) or treatment with chemotherapy, hormonal therapy or radiation therapy for cancer up to 12 months before the index date will be excluded.
- Men with Paget's disease during the 12-month period prior to the index date will also be excluded.
- Inclusion criteria for Men and Women Who Receive Prolia With Glucocorticoid Exd Exposure • Men and women identified from Medicare or Optum Research Database who are ≥65 years old (or ≥30 years old in Optum) on or before receiving at least 1 denosumab 60 mg injection or fill after approval date of Prolia for treatment of glucocorticoid-induced osteoporosis (18 May 2018) will be included. This includes both new and prevalent users of denosumab. The index date is defined as the date of the first denosumab administration on or after the approval date fulfilling both the database specific age, 12-month enrollment criteria, and has received a 90-day average daily dose equivalent ≥7.5 mg of prednisone at any time during the previous 12 months.
- Exclusion Criteria for Men and Women Who Receive Prolia With Glucocorticoid Exposure
- Men and women with a diagnosis of malignancy (excluding non-melanoma skin cancer) or treatment with chemotherapy, hormonal therapy or radiation therapy for cancer up to 12 months before the index date will be excluded. Men and women with Paget's disease during the 12-month period prior to the index date will also be excluded. The exclusion of subjects with cancer or Paget's disease will ensure that subjects included in the substudy are receiving denosumab for the treatment of osteoporosis, and not for other indications.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| denosumabsubcutaneous injection | Drug | Men with osteoporosis, Prolia for unapproved indications, Women with post menopausal osteoporosis |
| bisphosphonateThe assessment of bisphosphonates includes branded oral bisphosphonates (eg, alendronate [Fosamax®], risedronate [Actonel®], ibandronate [Boniva®/Bonviva®] oral); generic bisphosphonates, including alendronate, neridodronate, and olpadronate; intravenous bisphosphonates including ibandronate IV, and zoledronate [Reclast®/Aclasta®]. | Drug | Women with post menopausal osteoporosis |
Primary outcome
Incidence rates of Adverse Events of Special Interest (AESI)
Time frame: Up to 10 years
Incidence rates of AESI (per 100,000 Person-years) will be assessed in postmenopausal women with osteoporosis (PMO) and by exposure cohort (denosumab or bisphosphonates)
Characteristics and Adverse Events of Special Interest (AESI) risk factors
Time frame: Up to 10 years
Describe characteristics, clinical features, and AESI risk factors in women with PMO exposed to denosumab, women with PMO exposed to bisphosphonates, and all women with PMO.
Compare the incidence of the Adverse Events of Special Interests
Time frame: Up to 10 years
Compare the incidence of the AESI in women with PMO exposed to denosumab to that in women with PMO exposed to bisphosphonates.
Describe incidence rates of Adverse Events of Special Interest (AESI)
Time frame: Up to 10 years
Describe incidence rates of AESI in postmenopausal women.
Describe denosumab utilization patterns
Time frame: Up to 10 years
Describe denosumab utilization patterns in patients who receive denosumab therapy for treatment of PMO.
Describe Prolia utilization patterns
Time frame: Up to 10 years
Describe Prolia utilization patterns in patients who receive Prolia therapy for unapproved indications (indication, dosage, frequency).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2024.
- Background: PubMed 23857864Xue F, Ma H, Stehman-Breen C, Haller C, Katz L, Wagman RB, Critchlow CW; Denosumab Global Safety Assessment Team. Design and methods of a postmarketing pharmacoepidemiology study assessing long-term safety of Prolia(R) (denosumab) for the treatment of postmenopausal osteoporosis. Pharmacoepidemiol Drug Saf. 2013 Oct;22(10):1107-14. doi: 10.1002/pds.3477. Epub 2013 Jul 15.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
Questions about this trial
What is this clinical trial studying?
An observational study of Osteoporosis, run by Amgen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence rates of Adverse Events of Special Interest (AESI) (time frame: Up to 10 years). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02520362, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2024.