A High-resolution Peripheral Quantitative Computed Tomography Study in Postmenopausal Women Previously Treated With Denosumab

Study Overview
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Brief Summary
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To evaluate the combined effect of denosumab treatment and discontinuation on cortical thickness at the distal radius by High Resolution-Peripheral Quantitative Computed Tomography (HR-pQCT). Participants randomized to either denosumab or placebo in the 20050179 (NCT00293813) study who completed that study (ie, attended an end of study visit) can be included in this study. At least 12 months should have elapsed since the patient's 20050179 end of study visit.

Official Title
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A HR-pQCT Study in Postmenopausal Women Previously Treated With Denosumab

Conditions
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Low Bone Mass, Low Bone Mineral Density, Osteoporosis, Postmenopausal Osteoporosis

Intervention / Treatment
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* Procedure: high-resolution peripheral quantitative computed tomography (HR-pQCT)
* Procedure: Dual energy X-ray absorptiometry (DXA)
* Biological: Denosumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory, postmenopausal women Randomized to either denosumab or placebo in the 20050179 (NCT00293813) study and completed that study (ie, attended an end of study visit) At least 12 months have elapsed since their end of 20050179 study visit Provide signed informed consent Exclusion Criteria: Subjects who failed to receive both doses of denosumab (or SQ [subcutaneous] placebo) during the 20050179 study Subjects who were randomized to the alendronate arm during the 20050179 study Subjects diagnosed with any of the following conditions following completion of the 20050179 study: Hyperthyroidism Hyperparathyroidism Malignancy within the last 5 years (except cervical carcinoma in situ or basal cell carcinoma) Any condition that required chronic (greater than three months cumulative and greater than 5 mg/day) glucocorticoid therapy Other diseases which affect bone metabolism Self-reported alcohol or drug abuse within the previous 12 months 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 Received any investigational product other than denosumab in two years before the screening visit. Received > 3 months (or equivalent) of osteoporosis treatment since having completed the 20050179 study. Current use of the following osteoporosis agents: bisphosphonates, calcitonin, fluoride, parathyroid hormone analogue, selective estrogen receptor modulators, systemic oral or transdermal estrogen (except vaginal preparations and estrogen creams which are acceptable), strontium or tibolone. Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s) (other than Amgen trial 20080287), or subject is receiving other investigational agent(s).
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm 1<br>Participants who were randomized to either denosumab or placebo in Study 20050179 and at least 12 months had elapsed from their 20050179 end-of-study visit had dual energy X-ray absorptiometry (DXA) of the forearm and HR-pQCT of the tibia and radius on Day 1 of this study. No study drug was administered. | Procedure: high-resolution peripheral quantitative computed tomography (HR-pQCT)<br>* Bone densitometry and microarchitecture assessments of the distal radius and the distal tibia by HR-pQCT on Day 1.<br>Procedure: Dual energy X-ray absorptiometry (DXA)<br>* Bone densitometry assessments of the forearm by DXA on day 1.<br>Biological: Denosumab<br>* Denosumab 60 mg subcutaneously every 6 months in the previous study<br>Drug: Placebo<br>* Placebo to denosumab subcutaneously every 6 months in the previous study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From the Parent Study Baseline in Cortical Thickness at the Distal Radius by HR-pQCT | Percent change from the 20050179 Baseline in cortical thickness at the distal radius as determined by high-resolution peripheral quantitative computed tomography (HR-pQCT) at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179. | Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From the Parent Study Baseline in Total Bone Mineral Density (BMD) at the Distal Radius by HR-pQCT | Percent change from the 20050179 Baseline in total BMD at the distal radius as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179. | Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months. | 
| Percent Change From the Parent Study Baseline in Cortical BMD at the Distal Radius by HR-pQCT | Percent change from the 20050179 Baseline in cortical BMD at the distal radius as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179. | Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months. | 
| Percent Change From the Parent Study Baseline in Trabecular BMD at the Distal Radius by HR-pQCT | Percent change from the 20050179 Baseline in trabecular BMD at the distal radius as determined by HR-pQCT at an average of 32 months since last subcutaneous dose of denosumab or placebo in study 20050179. | Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months. | 
| Percent Change From the Parent Study Baseline in Cortical Thickness at the Distal Tibia by HR-pQCT | Percent change from the 20050179 Baseline in cortical thickness at the distal tibia as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179. | Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months. | 
| Percent Change From the Parent Study Baseline in Total BMD at the Distal Tibia by HR-pQCT | Percent change from the 20050179 Baseline in total BMD at the distal tibia as determined by HR-pQCT at an average of 32 months since last subcutaneous dose of denosumab or placebo in study 20050179. | Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months. | 
| Percent Change From the Parent Study Baseline in Cortical BMD at the Distal Tibia by HR-pQCT | Percent change from the 20050179 Baseline in cortical BMD at the distal tibia as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179. | Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months. | 
| Percent Change From the Parent Study Baseline in Trabecular BMD at the Distal Tibia by HR-pQCT | Percent change from the 20050179 Baseline in trabecular BMD at the distal tibia as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179. | Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months. | 
| Percent Change of Distal 1/3 Radius BMD From the Parent Study Baseline by DXA | Percent change of distal 1/3 radius BMD from the 20050179 Baseline as determined by dual energy X-ray absorptiometry (DXA) at an average of 32 months since last subcutaneous dose of denosumab or placebo in study 20050179. | Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months. | 
| Percent Change of Ultradistal Radius BMD From the Parent Study Baseline by DXA | Percent change of ultradistal radius BMD from the 20050179 Baseline as determined by DXA at an average of 32 months since last the subcutaneous dose of denosumab or placebo in study 20050179. | Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months. | 
| Percent Change of Total Radius BMD From the Parent Study Baseline by DXA | Percent change of total radius BMD from the 20050179 Baseline as determined by DXA at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179. | Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months. | 
| Actual Value of Serum Type I C-telopeptide | Actual value of Serum Type I C-telopeptide measured from blood samples taken on Day 1 (an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179). | Day 1 | 
| Actual Value of Procollagen Type 1 N-terminal Peptide | Actual value of Type 1 N-terminal Peptide as measured from blood samples taken on Day 1 (an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179). | Day 1 |