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Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density

Primary Purpose

Low Bone Mineral Density

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Placebo
Denosumab
Alendronate
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Low Bone Mineral Density focused on measuring bone loss, osteoporosis

Eligibility Criteria

undefined - 80 Years (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria women not more than 80 years of age on date of randomization ≥ 1 year postmenopausal on date of randomization ambulatory if ≤ 60 years of age, or had or would require a bilateral oophorectomy, serum follicle stimulating hormone (FSH) > 50 mU/mL or serum estradiol < 20 pg/mL low BMD (BMD T-score ≤ -1.8 at any 1 of the following sites: lumbar spine, femoral neck, or total hip; BMD T-scores must not have been < -4.0 at the lumbar spine or - 3.5 at the femoral neck or total hip) before any study-specific procedure, including the screening dual X-ray absorptiometry (DXA) scan, gave informed consent for participation in the study. Exclusion Criteria fluoride treatment for osteoporosis within the 2 years before the enrollment date bisphosphonate use within the 12 months before the enrollment date administration of the following medications within the 6 months before the enrollment date tibolone Parathyroid hormone (PTH) (or any derivative) systemic glucocorticosteroids (> 5 mg oral prednisone equivalent per day for > 10 days) inhaled corticosteroids (> 2000 μg per day for > 10 days) anabolic steroids or testosterone administration of the following medications within the 3 months before the enrollment date systemic hormone replacement therapy selective estrogen receptor modulators calcitonin calcitriol current hyper- or hypothyroidism (allowed if stable on thyroid replacement therapy and thyroid-stimulating hormone was within the normal range) current hyper- or hypoparathyroidism albumin-adjusted serum calcium < 8.5 mg/dL (< 2.125 mol/L) osteomalacia rheumatoid arthritis Paget's disease malignancy within the 5 years before enrollment (except cervical carcinoma in situ or basal cell carcinoma, which were acceptable) renal disease; ie, creatinine clearance ≤ 35 mL/min any bone disease, other than osteoporosis, which could interfere with the interpretation of the findings (eg, osteogenesis imperfecta or osteopetrosis) malabsorption syndrome weight, height, or girth that could preclude accurate DXA measurements < 2 lumbar vertebrae (L1 through L4) evaluable by DXA recent long bone fracture (within 6 months) osteoporotic-related fracture (ie, crush or wedge vertebral fracture or hip fracture) known or suspected to have occurred within 2 years of randomization > 1 single, grade 1 vertebral fracture currently enrolled in or had participated within the previous 30 days in other investigational device or drug trial(s) (For some trials, this may have been allowed after discussion and written approval from Amgen.) known sensitivity to mammalian-derived drug preparations (eg, Herceptin®) any organic or psychiatric disorder, serum chemistry, or hematology that, in the opinion of the investigator, could have prevented the subject from completing the study or have interfered with the interpretation of the study results self-reported alcohol or drug abuse within the previous 12 months any disorder that compromised the ability to give truly informed consent for participation in the study previous administration of denosumab known sensitivity or contraindication to alendronate known sensitivity or contraindication to tetracycline derivatives (subjects in the biopsy substudy only).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm 8

    Arm 9

    Arm Type

    Placebo Comparator

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Active Comparator

    Arm Label

    Placebo

    Denosumab 6 mg every 3 months

    Denosumab 14 mg every 3 months

    Denosumab 30 mg every 3 months

    Denosumab 14 mg every 6 months

    Denosumab 60 mg every 6 months

    Denosumab 100 mg every 6 months

    Denosumab 210 mg every 6 months

    Alendronate 70 mg

    Arm Description

    Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42.

    Participants received denosumab 6 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.

    Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.

    Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42.

    Participants received denosumab 14 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.

    Participants received denosumab 60 mg SC every 6 months until Month 42.

    Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.

    Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42.

    Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.

    Outcomes

    Primary Outcome Measures

    Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

    Secondary Outcome Measures

    Serum CTX Percent Change From Baseline at Month 12
    Serum C-Telopeptide (CTX). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Urine NTX/Creatinine Percent Change From Baseline at Month 12
    Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Serum CTX Percent Change From Baseline at Month 24
    Serum C-Telopeptide (CTX). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Serum CTX Percent Change From Baseline at Month 36
    Serum C-Telopeptide (CTX). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Serum CTX Percent Change From Baseline at Month 42
    Serum C-Telopeptide (CTX). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Serum CTX Percent Change From Baseline at Month 48
    Serum C-Telopeptide (CTX). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Urine NTX/Creatinine Percent Change From Baseline at Month 24
    Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Urine NTX/Creatinine Percent Change From Baseline at Month 36
    Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Urine NTX/Creatinine Percent Change From Baseline at Month 42
    Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Urine NTX/Creatinine Percent Change From Baseline at Month 48
    Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Total Hip Bone Mineral Density Percent Change From Baseline at Month 12
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Total Hip Bone Mineral Density Percent Change From Baseline at Month 24
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Total Hip Bone Mineral Density Percent Change From Baseline at Month 36
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Total Hip Bone Mineral Density Percent Change From Baseline at Month 42
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Total Hip Bone Mineral Density Percent Change From Baseline at Month 48
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Total Body Bone Mineral Density Percent Change From Baseline at Month 12
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Total Body Bone Mineral Density Percent Change From Baseline at Month 24
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Total Body Bone Mineral Density Percent Change From Baseline at Month 36
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Total Body Bone Mineral Density Percent Change From Baseline at Month 42
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Total Body Bone Mineral Density Percent Change From Baseline at Month 48
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12
    Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24
    Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36
    Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42
    Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48
    Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

    Full Information

    First Posted
    August 6, 2002
    Last Updated
    September 6, 2013
    Sponsor
    Amgen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00043186
    Brief Title
    Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density
    Official Title
    A Randomized, Double-Blind, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of AMG 162 in the Treatment of Postmenopausal Women With Low Bone Mineral Density
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2013
    Overall Recruitment Status
    Completed
    Study Start Date
    May 2002 (undefined)
    Primary Completion Date
    April 2007 (Actual)
    Study Completion Date
    June 2007 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Amgen

    4. Oversight

    5. Study Description

    Brief Summary
    To determine the effect of denosumab treatment compared with placebo over 12 months on bone mineral density (BMD) of the lumbar spine in postmenopausal women with low BMD. The clinical hypothesis is that denosumab subcutaneous injections administered every 3 or 6 months for 12 months will significantly increase lumbar spine bone mineral density and will be well tolerated.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Low Bone Mineral Density
    Keywords
    bone loss, osteoporosis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    412 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42.
    Arm Title
    Denosumab 6 mg every 3 months
    Arm Type
    Experimental
    Arm Description
    Participants received denosumab 6 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
    Arm Title
    Denosumab 14 mg every 3 months
    Arm Type
    Experimental
    Arm Description
    Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
    Arm Title
    Denosumab 30 mg every 3 months
    Arm Type
    Experimental
    Arm Description
    Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42.
    Arm Title
    Denosumab 14 mg every 6 months
    Arm Type
    Experimental
    Arm Description
    Participants received denosumab 14 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
    Arm Title
    Denosumab 60 mg every 6 months
    Arm Type
    Experimental
    Arm Description
    Participants received denosumab 60 mg SC every 6 months until Month 42.
    Arm Title
    Denosumab 100 mg every 6 months
    Arm Type
    Experimental
    Arm Description
    Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
    Arm Title
    Denosumab 210 mg every 6 months
    Arm Type
    Experimental
    Arm Description
    Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42.
    Arm Title
    Alendronate 70 mg
    Arm Type
    Active Comparator
    Arm Description
    Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo subcutaneous injection
    Intervention Type
    Drug
    Intervention Name(s)
    Denosumab
    Other Intervention Name(s)
    AMG 162, Prolia
    Intervention Description
    Denosumab for subcutaneous injection
    Intervention Type
    Drug
    Intervention Name(s)
    Alendronate
    Other Intervention Name(s)
    Fosamax
    Intervention Description
    Alendronate 70 mg tablets
    Primary Outcome Measure Information:
    Title
    Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and Month 12
    Secondary Outcome Measure Information:
    Title
    Serum CTX Percent Change From Baseline at Month 12
    Description
    Serum C-Telopeptide (CTX). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and Month 12
    Title
    Urine NTX/Creatinine Percent Change From Baseline at Month 12
    Description
    Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and Month 12
    Title
    Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and Month 12
    Title
    Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 24 months
    Title
    Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 36 months
    Title
    Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 42 months
    Title
    Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 48 months
    Title
    Serum CTX Percent Change From Baseline at Month 24
    Description
    Serum C-Telopeptide (CTX). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 24 months
    Title
    Serum CTX Percent Change From Baseline at Month 36
    Description
    Serum C-Telopeptide (CTX). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 36 months
    Title
    Serum CTX Percent Change From Baseline at Month 42
    Description
    Serum C-Telopeptide (CTX). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 42 months
    Title
    Serum CTX Percent Change From Baseline at Month 48
    Description
    Serum C-Telopeptide (CTX). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 48 months
    Title
    Urine NTX/Creatinine Percent Change From Baseline at Month 24
    Description
    Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 24 months
    Title
    Urine NTX/Creatinine Percent Change From Baseline at Month 36
    Description
    Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 36 months
    Title
    Urine NTX/Creatinine Percent Change From Baseline at Month 42
    Description
    Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 42 months
    Title
    Urine NTX/Creatinine Percent Change From Baseline at Month 48
    Description
    Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 48 months
    Title
    Total Hip Bone Mineral Density Percent Change From Baseline at Month 12
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 12 months
    Title
    Total Hip Bone Mineral Density Percent Change From Baseline at Month 24
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 24 months
    Title
    Total Hip Bone Mineral Density Percent Change From Baseline at Month 36
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 36 months
    Title
    Total Hip Bone Mineral Density Percent Change From Baseline at Month 42
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 42 months
    Title
    Total Hip Bone Mineral Density Percent Change From Baseline at Month 48
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 48 months
    Title
    Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 12 months
    Title
    Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 24 months
    Title
    Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 36 months
    Title
    Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 42 months
    Title
    Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 48 months
    Title
    Total Body Bone Mineral Density Percent Change From Baseline at Month 12
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 12 months
    Title
    Total Body Bone Mineral Density Percent Change From Baseline at Month 24
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 24 months
    Title
    Total Body Bone Mineral Density Percent Change From Baseline at Month 36
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 36 months
    Title
    Total Body Bone Mineral Density Percent Change From Baseline at Month 42
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 42 months
    Title
    Total Body Bone Mineral Density Percent Change From Baseline at Month 48
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 48 months
    Title
    Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12
    Description
    Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 12 months
    Title
    Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24
    Description
    Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 24 months
    Title
    Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36
    Description
    Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 36 months
    Title
    Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42
    Description
    Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 42 months
    Title
    Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48
    Description
    Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline and 48 months

    10. Eligibility

    Sex
    Female
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria women not more than 80 years of age on date of randomization ≥ 1 year postmenopausal on date of randomization ambulatory if ≤ 60 years of age, or had or would require a bilateral oophorectomy, serum follicle stimulating hormone (FSH) > 50 mU/mL or serum estradiol < 20 pg/mL low BMD (BMD T-score ≤ -1.8 at any 1 of the following sites: lumbar spine, femoral neck, or total hip; BMD T-scores must not have been < -4.0 at the lumbar spine or - 3.5 at the femoral neck or total hip) before any study-specific procedure, including the screening dual X-ray absorptiometry (DXA) scan, gave informed consent for participation in the study. Exclusion Criteria fluoride treatment for osteoporosis within the 2 years before the enrollment date bisphosphonate use within the 12 months before the enrollment date administration of the following medications within the 6 months before the enrollment date tibolone Parathyroid hormone (PTH) (or any derivative) systemic glucocorticosteroids (> 5 mg oral prednisone equivalent per day for > 10 days) inhaled corticosteroids (> 2000 μg per day for > 10 days) anabolic steroids or testosterone administration of the following medications within the 3 months before the enrollment date systemic hormone replacement therapy selective estrogen receptor modulators calcitonin calcitriol current hyper- or hypothyroidism (allowed if stable on thyroid replacement therapy and thyroid-stimulating hormone was within the normal range) current hyper- or hypoparathyroidism albumin-adjusted serum calcium < 8.5 mg/dL (< 2.125 mol/L) osteomalacia rheumatoid arthritis Paget's disease malignancy within the 5 years before enrollment (except cervical carcinoma in situ or basal cell carcinoma, which were acceptable) renal disease; ie, creatinine clearance ≤ 35 mL/min any bone disease, other than osteoporosis, which could interfere with the interpretation of the findings (eg, osteogenesis imperfecta or osteopetrosis) malabsorption syndrome weight, height, or girth that could preclude accurate DXA measurements < 2 lumbar vertebrae (L1 through L4) evaluable by DXA recent long bone fracture (within 6 months) osteoporotic-related fracture (ie, crush or wedge vertebral fracture or hip fracture) known or suspected to have occurred within 2 years of randomization > 1 single, grade 1 vertebral fracture currently enrolled in or had participated within the previous 30 days in other investigational device or drug trial(s) (For some trials, this may have been allowed after discussion and written approval from Amgen.) known sensitivity to mammalian-derived drug preparations (eg, Herceptin®) any organic or psychiatric disorder, serum chemistry, or hematology that, in the opinion of the investigator, could have prevented the subject from completing the study or have interfered with the interpretation of the study results self-reported alcohol or drug abuse within the previous 12 months any disorder that compromised the ability to give truly informed consent for participation in the study previous administration of denosumab known sensitivity or contraindication to alendronate known sensitivity or contraindication to tetracycline derivatives (subjects in the biopsy substudy only).
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    MD
    Organizational Affiliation
    Amgen
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    18495508
    Citation
    Beck TJ, Lewiecki EM, Miller PD, Felsenberg D, Liu Y, Ding B, Libanati C. Effects of denosumab on the geometry of the proximal femur in postmenopausal women in comparison with alendronate. J Clin Densitom. 2008 Jul-Sep;11(3):351-9. doi: 10.1016/j.jocd.2008.04.001. Epub 2008 May 20.
    Results Reference
    result
    PubMed Identifier
    17708711
    Citation
    Lewiecki EM, Miller PD, McClung MR, Cohen SB, Bolognese MA, Liu Y, Wang A, Siddhanti S, Fitzpatrick LA; AMG 162 Bone Loss Study Group. Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res. 2007 Dec;22(12):1832-41. doi: 10.1359/jbmr.070809.
    Results Reference
    result
    PubMed Identifier
    16495394
    Citation
    McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ; AMG 162 Bone Loss Study Group. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006 Feb 23;354(8):821-31. doi: 10.1056/NEJMoa044459.
    Results Reference
    result
    PubMed Identifier
    18539106
    Citation
    Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008 Aug;43(2):222-229. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26.
    Results Reference
    result
    PubMed Identifier
    19732857
    Citation
    Peterson MC, Riggs MM. A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling. Bone. 2010 Jan;46(1):49-63. doi: 10.1016/j.bone.2009.08.053. Epub 2009 Sep 2.
    Results Reference
    result
    Links:
    URL
    http://www.amgentrials.com
    Description
    AmgenTrials clinical trials website

    Learn more about this trial

    Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density

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