An Open Label, Single Arm, Extension Study to Evaluate the Long Term Safety and Sustained Efficacy of Denosumab (AMG162) in the Treatment of Postmenopausal Osteoporosis
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Osteopenia
- Sponsor
- Amgen
- Enrollment
- 4550
- Primary Endpoint
- Number of Participants With Laboratory Toxicities of Grade ≥ 3
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The primary objective was to describe the safety and tolerability of up to 10 years or 7 years denosumab administration as measured by adverse event monitoring, immunogenicity and safety laboratory parameters in participants who previously received denosumab or placebo, respectively.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Number of Participants With Laboratory Toxicities of Grade ≥ 3
Time Frame: 84 months
Laboratory toxicity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 3 indicates severe toxicity and Grade 4 indicates life-threatening toxicity.
Number of Participants With Adverse Events (AEs)
Time Frame: 84 months
A serious adverse event (SAE) is defined as an adverse event that: • is fatal • is life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • is other significant medical hazard. Treatment-related adverse events includes only events for which the investigator indicated there was a reasonable possibility they may have been caused by study drug. The following were classified as adverse events of interest (events that are considered to be identified or potential risks of denosumab treatment): positively adjudicated osteonecrosis of the jaw, positively adjudicated atypical femoral fracture, hypocalcemia, adverse events potentially related to hypersensitivity, serious infection (including bacterial cellulitis), malignancy, cardiac disorders, vascular disorders, fracture healing complications, eczema, acute pancreatitis, and musculoskeletal pain.
Number of Participants With Antibodies to Denosumab
Time Frame: Every 12 months through Month 84
Secondary Outcomes
- Percent Change From Baseline in Lumbar Spine Bone Mineral Density by Visit(Baseline (of extension study) and months 12, 24, 36, 60 and 84)
- Percent Change From Study 20030216 Baseline in Lumbar Spine Bone Mineral Density by Visit(Study 20030216 baseline and extension study months 12, 24, 36, 60 and 84)
- Bone Histomorphometry: Trabecular Thickness(Month 24 and month 84)
- Bone Histomorphometry: Cortical Width(Month 24 and month 84)
- Percent Change From Baseline in Total Hip Bone Mineral Density by Visit(Baseline (of extension study) and months 12, 24, 36, 60 and 84)
- Percent Change From Baseline in Femoral Neck Bone Mineral Density by Visit(Baseline (of extension study) and months 12, 24, 36, 60 and 84)
- Percent Change From Baseline in 1/3 Radius Bone Mineral Density by Visit(Baseline (of extension study) and months 12, 24, 36, 60 and 84)
- Number of Participants With New Vertebral Fractures(84 months)
- Percent Change From Baseline in Albumin-adjusted Serum Calcium at Day 10(Baseline (of extension study) and day 10)
- Serum Denosumab Concentration(Baseline (pre-dose in extension study), day 10, and Months 3, 4 and 6 (pre-dose))
- Bone Histomorphometry: Cancellous Bone Volume(Month 24 and month 84)
- Bone Histomorphometry: Osteoblast - Osteoid Interface(Month 24 and month 84)
- Percent Change From Study 20030216 Baseline in Total Hip BMD by Visit(Study 20030216 baseline and extension study months 12, 24, 36, 60 and 84)
- Percent Change From Study 20030216 Baseline in Femoral Neck BMD by Visit(Study 20030216 baseline and extension study months 12, 24, 36, 60 and 84)
- Percent Change From Study 20030216 Baseline in 1/3 Radius BMD by Visit(Study 20030216 baseline and extension study months 12, 24, 36, 60, and 84)
- Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) by Visit(Baseline (of extension study), day 10, and months 6, 12, 24, 36, 48, 60, 72, and 84)
- Bone Histomorphometry: Osteoid Thickness(Month 24 and month 84)
- Bone Histomorphometry: Eroded Surface/Bone Surface(Month 24 and month 84)
- Bone Histomorphometry: Single-label Surface(Month 24 and month 84)
- Bone Histomorphometry: Double-label Surface(Month 24 and month 84)
- Bone Histomorphometry: Osteoid Volume(Month 24 and month 84)
- Number of Participants With Non-Vertebral Fractures(84 months)
- Percent Change From Study 20030216 Baseline in CTX-1 by Visit(Study 20030216 Baseline and extension study day 10, and months 6, 12, 24, 36, 48, 60, 72, and 84)
- Percent Change From Study 20030216 Baseline in P1NP by Visit(Study 20030216 Baseline and extension study day 10, and months 6, 12, 24, 36, 48, 60, 72, and 84)
- Bone Histomorphometry: Trabecular Separation(Month 24 and month 84)
- Bone Histomorphometry: Mineral Apposition Rate(Month 24 and month 84)
- Bone Histomorphometry: Formation Period(Month 24 and month 84)
- Bone Histology at Month 84(Month 84)
- Percent Change From Baseline in C-Telopeptide 1 (CTX-1) by Visit(Baseline (of extension study), day 10, and months 6, 12, 24, 36, 48, 60, 72, and 84)
- Bone Histomorphometry: Trabecular Number(Month 24 and month 84)
- Bone Histomorphometry: Cancellous Bone Volume by TRAP Histomorphometry(Month 24 and month 84)
- Bone Histomorphometry: Osteoclast Number by TRAP - Length Based(Month 24 and month 84)
- Bone Histomorphometry: Bone Formation Rate - Surface Based(Month 24 and month 84)
- Bone Histomorphometry: Activation Frequency(Month 24 and month 84)
- Bone Histomorphometry: Surface Density(Month 24 and month 84)
- Bone Histomorphometry: Osteoid Surface(Month 24 and month 84)
- Bone Histomorphometry: Osteoclast Number - Surface Based(Month 24 and month 84)
- Bone Histomorphometry: Osteoclast Number by TRAP - Surface Based(Month 24 and month 84)
- Bone Histomorphometry: Mineralizing Surface(Month 24 and month 84)
- Bone Histomorphometry: Adjusted Apposition Rate(Month 24 and month 84)
- Bone Histology at Month 24(Month 24)
- Bone Histomorphometry: Wall Thickness(Month 24 and month 84)
- Bone Histomorphometry: Osteoclast Number - Length Based(Month 24 and month 84)
- Bone Histomorphometry: Bone Formation Rate - Volume Based(Month 24 and month 84)
- Bone Histomorphometry: Mineralization Lag Time(Month 24 and month 84)