Denosumab Safety Assessment in Multiple Observational Databases

Completed

• Conditions: Osteoporosis
• Interventions: Drug: denosumab; Drug: bisphosphonate

• Registration Number: NCT02520362
• Lead Sponsor: Amgen

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.

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 Timeline

• Study Start: 2010-05-31
• Study First Submitted: 2015-05-07
• Study First Submitted QC: 2015-08-10
• Study First Posted: 2015-08-11
• Primary Completion: 2023-07-21
• Study Completion: 2023-07-21
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-31
• Last Update Posted: 2024-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 517991

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Women with post menopausal osteoporosis	bisphosphonate	Women with post menopausal osteoporosis
Women with post menopausal osteoporosis	denosumab	Women with post menopausal osteoporosis
Men with osteoporosis	denosumab	Men with osteoporosis treated with denosumab
Prolia for unapproved indications	denosumab	Patients who receive Prolia for unapproved indications

Primary Outcome Measures

Name	Time	Method
Describe denosumab utilization patterns	Up to 10 years	Describe denosumab utilization patterns in patients who receive denosumab therapy for treatment of PMO.
Describe incidence rates of Adverse Events of Special Interest (AESI)	Up to 10 years	Describe incidence rates of AESI in postmenopausal women.
Characteristics and Adverse Events of Special Interest (AESI) risk factors	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.
Describe Prolia utilization patterns	Up to 10 years	Describe Prolia utilization patterns in patients who receive Prolia therapy for unapproved indications (indication, dosage, frequency).
Incidence rates of Adverse Events of Special Interest (AESI)	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)
Compare the incidence of the Adverse Events of Special Interests	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.