Denosumab Safety Assessment in Multiple Observational Databases

NCT02520362 | Completed

• 1 other identifier: 20090522
• Study Type: observational
• Target: 517,991
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Osteoporosis

Outcome Measures

Primary Outcomes (6)

• 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)

  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.

  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.

  Up to 10 years

• Describe incidence rates of Adverse Events of Special Interest (AESI)

  Describe incidence rates of AESI in postmenopausal women.

  Up to 10 years

• Describe denosumab utilization patterns

  Describe denosumab utilization patterns in patients who receive denosumab therapy for treatment of PMO.

  Up to 10 years

• Describe Prolia utilization patterns

  Describe Prolia utilization patterns in patients who receive Prolia therapy for unapproved indications (indication, dosage, frequency).

  Up to 10 years

Study Arms (5)

Postmenopausal Women

Postmenopausal Women

Women with post menopausal osteoporosis

Women with post menopausal osteoporosis

Drug: denosumab; Drug: bisphosphonate

Prolia for unapproved indications

Patients who receive Prolia for unapproved indications

Drug: denosumab

Men with osteoporosis

Men with osteoporosis treated with denosumab

Drug: denosumab

Men and women who receive Prolia with Glucocorticoid exposure

Drug: denosumab subcutaneous injection

Interventions

denosumab DRUG

subcutaneous injection

Men with osteoporosis; Prolia for unapproved indications; Women with post menopausal osteoporosis

bisphosphonate DRUG

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 \[Reclast®/Aclasta®\].

Women with post menopausal osteoporosis

Eligibility Criteria

• Age: 30 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• Postmenopausal women: Postmenopausal status will be determined based on age and defined as women ≥ 55 years old. For the Medicare database, only women ≥ 65 years old will be included in the analysis, given that generally all individuals in the US ≥ 65 years old are eligible for Medicare coverage and data on postmenopausal women less than 65 years old will be available for only a small number of women meeting other specialized eligibility criteria.
• Women with Post Menopausal Osteoporosis: The presence of Post Menopausal Osteoporosis will be determined utilizing an algorithm based upon definition of postmenopausal women (≥ 65 years old in Medicare or ≥ 55 years old in other data systems), diagnostic codes indicating osteoporosis, diagnostic codes indicating osteoporotic fracture, and/or relevant postmenopausal osteoporosis treatment codes.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead
• Aarhus University Hospital: collaborator
• Optum, Inc.: collaborator
• University of Alabama at Birmingham: collaborator

Related Publications (1)

• 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.

  PMID: 23857864 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Osteoporosis

Interventions

Denosumab; Diphosphonates

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Organophosphonates; Organophosphorus Compounds; Organic Chemicals

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2015
• First Posted: August 11, 2015
• Study Start: May 31, 2010
• Primary Completion: July 21, 2023
• Study Completion: July 21, 2023
• Last Updated: November 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.