Phase 3
Completed N=4,550
Extension Study to Evaluate the Long Term Safety and Efficacy of Denosumab in the Treatment of Osteoporosis
Source: ClinicalTrials.gov NCT00523341 ↗Enrolled (actual)
4,550
Serious AEs
43.1%
Results posted
Jul 2016
Primary outcomePrimary: Number of Participants With Adverse Events (AEs) — 2070; 2173; 945; 1014 participants
◆ Published Evidence
Highly cited
344citations · ~25 / year
Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension.
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.
Linked Publications (5)
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Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension.
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The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension.
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Denosumab Safety and Efficacy Among Participants in the FREEDOM Extension Study With Mild to Moderate Chronic Kidney Disease.
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Denosumab in postmenopausal women with osteoporosis and diabetes: Subgroup analysis of FREEDOM and FREEDOM extension.
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Favorable skeletal benefit/risk of long-term denosumab therapy: A virtual-twin analysis of fractures prevented relative to skeletal safety events observed.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs) |
2070; 2173; 945; 1014; 101; 108 | — |
| PRIMARY Number of Participants With Laboratory Toxicities of Grade ≥ 3 |
28; 25; 1; 0; 9; 11 | — |
| PRIMARY Number of Participants With Antibodies to Denosumab |
1; 0 | — |
| SECONDARY Percent Change From Baseline in Lumbar Spine Bone Mineral Density by Visit |
5.2; 2.0; 7.7; 3.5; 9.4; 4.9 | — |
| SECONDARY Percent Change From Baseline in Total Hip Bone Mineral Density by Visit |
3.0; 0.8; 4.1; 1.4; 4.9; 1.8 | — |
| SECONDARY Percent Change From Baseline in Femoral Neck Bone Mineral Density by Visit |
2.1; 0.8; 3.2; 1.2; 4.0; 1.7 | — |
| SECONDARY Percent Change From Baseline in 1/3 Radius Bone Mineral Density by Visit |
0.3; 0.6; 0.2; 0.2; 1.3; 0.6 | — |
| SECONDARY Percent Change From Study 20030216 Baseline in Lumbar Spine Bone Mineral Density by Visit |
5.9; 11.9; 8.4; 13.7; 10.1; 15.2 | — |
| SECONDARY Percent Change From Study 20030216 Baseline in Total Hip BMD by Visit |
1.7; 6.4; 2.9; 7.1; 3.6; 7.5 | — |
| SECONDARY Percent Change From Study 20030216 Baseline in Femoral Neck BMD by Visit |
1.4; 5.8; 2.6; 6.2; 3.4; 6.7 | — |
| SECONDARY Percent Change From Study 20030216 Baseline in 1/3 Radius BMD by Visit |
-1.0; 2.6; -1.2; 2.1; -0.2; 2.4 | — |
| SECONDARY Number of Participants With New Vertebral Fractures |
145; 149 | — |
| SECONDARY Number of Participants With Non-Vertebral Fractures |
219; 172 | — |
| SECONDARY Percent Change From Baseline in C-Telopeptide 1 (CTX-1) by Visit |
-90; -72; -85; -26; -75; -13 | — |
| SECONDARY Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) by Visit |
6; 14; -71; -23; -67; 7 | — |
| SECONDARY Percent Change From Study 20030216 Baseline in CTX-1 by Visit |
-90; -91; -83; -77; -77; -63 | — |
| SECONDARY Percent Change From Study 20030216 Baseline in P1NP by Visit |
9; -59; -74; -75; -74; -63 | — |
| SECONDARY Percent Change From Baseline in Albumin-adjusted Serum Calcium at Day 10 |
-3.1; -2.0 | — |
| SECONDARY Serum Denosumab Concentration |
0; 113; 5890; 6010; 1000; 1190 | — |
| SECONDARY Bone Histomorphometry: Cancellous Bone Volume |
15.253; 14.640; NA; 16.358 | — |
| SECONDARY Bone Histomorphometry: Trabecular Number |
1.005; 0.904; NA; 1.235 | — |
| SECONDARY Bone Histomorphometry: Trabecular Separation |
919.693; 1033.416; NA; 708.669 | — |
| SECONDARY Bone Histomorphometry: Trabecular Thickness |
153.878; 156.335; NA; 132.965 | — |
| SECONDARY Bone Histomorphometry: Cortical Width |
622.22; 707.69; NA; 786.19 | — |
| SECONDARY Bone Histomorphometry: Cancellous Bone Volume by TRAP Histomorphometry |
16.678; 15.606; NA; 17.631 | — |
| SECONDARY Bone Histomorphometry: Surface Density |
2.009; 1.807; NA; 2.472 | — |
| SECONDARY Bone Histomorphometry: Osteoblast - Osteoid Interface |
22.124; 17.813; NA; 5.951 | — |
| SECONDARY Bone Histomorphometry: Osteoid Surface |
0.915; 0.982; NA; 0.421 | — |
| SECONDARY Bone Histomorphometry: Osteoid Thickness |
5.139; 4.548; NA; 4.108 | — |
| SECONDARY Bone Histomorphometry: Wall Thickness |
43.11; 49.74; NA; 39.59 | — |
| SECONDARY Bone Histomorphometry: Eroded Surface/Bone Surface |
0.414; 0.328; NA; 0.511 | — |
| SECONDARY Bone Histomorphometry: Osteoclast Number - Length Based |
0.086; 0.107; NA; 0.074 | — |
| SECONDARY Bone Histomorphometry: Osteoclast Number - Surface Based |
8.6; 10.7; NA; 7.4 | — |
| SECONDARY Bone Histomorphometry: Osteoclast Number by TRAP - Length Based |
0.096; 0.110; NA; 0.077 | — |
| SECONDARY Bone Histomorphometry: Osteoclast Number by TRAP - Surface Based |
9.6; 11.0; NA; 7.7 | — |
| SECONDARY Bone Histomorphometry: Single-label Surface |
0.304; 0.643; NA; 0.611 | — |
| SECONDARY Bone Histomorphometry: Double-label Surface |
0.258; 0.356; NA; 0.106 | — |
| SECONDARY Bone Histomorphometry: Mineralizing Surface |
0.406; 0.681; NA; 0.412 | — |
| SECONDARY Bone Histomorphometry: Mineral Apposition Rate |
0.616; 0.722; NA; 0.394 | — |
| SECONDARY Bone Histomorphometry: Adjusted Apposition Rate |
0.394; 0.517; NA; 0.818 | — |
| SECONDARY Bone Histomorphometry: Bone Formation Rate - Surface Based |
0.898; 2.153; NA; 0.691 | — |
| SECONDARY Bone Histomorphometry: Bone Formation Rate - Volume Based |
1.454; 3.162; NA; 1.071 | — |
| SECONDARY Bone Histomorphometry: Formation Period |
593.5; 287.3; NA; 229.7 | — |
| SECONDARY Bone Histomorphometry: Activation Frequency |
0.022; 0.045; NA; 0.014 | — |
| SECONDARY Bone Histomorphometry: Osteoid Volume |
0.108; 0.146; NA; 0.048 | — |
| SECONDARY Bone Histomorphometry: Mineralization Lag Time |
84.9; 54.3; NA; 52.3 | — |
| SECONDARY Bone Histology at Month 24 |
13; 28; 13; 28; 13; 23 | — |
| SECONDARY Bone Histology at Month 84 |
22; 22; 18; 0; 0; 0 | — |
Eligibility Criteria
Postmenopausal women who have attended the 20030216 (NCT00089791) study month 36 visit will be eligible to participate if they meet the inclusion and exclusion criteria given below.
Inclusion Criteria
- Subjects must sign the informed consent before any study specific procedures are performed and agree to receive denosumab 60 mg subcutaneous injection every 6 months
- Subjects must not have discontinued investigational product during the 20030216 study and must have attended the 20030216 study month 36 visit
- Subjects must be re-consented prior to (or at) the 24 month visit for participation beyond month 24.
Exclusion Criteria
- Permanently non-ambulatory subjects (use of an assistive device eg, cane, walker, etc. is permitted)
- Missed 2 or more investigational product doses during the 20030216 study
- Any disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or comply with study procedures
- Developed sensitivity to mammalian cell derived drug products during the 20030216 study
- Unable to tolerate calcium supplementation during the last 6 months of participation in the 20030216 study (between the month 30 and month 36 20030216 study visits)
- Currently receiving any investigational product other than denosumab or having received any investigational product during the 20030216 study
- Current use of the following osteoporosis agents: bisphosphonates, calcitonin, fluoride, parathyroid hormone, selective estrogen receptor modulators, systemic oral or transdermal estrogen (except vaginal preparations and estrogen creams which are acceptable), strontium, or tibolone
- For bone biopsy sub-study subjects only: known or suspected sensitivity or contraindication to tetracycline derivatives
Data sourced from ClinicalTrials.gov (NCT00523341) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.