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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00043186
First received: August 6, 2002
Last updated: September 6, 2013
Last verified: September 2013

August 6, 2002
September 6, 2013
May 2002
April 2007   (final data collection date for primary outcome measure)
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
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.
Not Provided
Complete list of historical versions of study NCT00043186 on ClinicalTrials.gov Archive Site
  • Serum CTX Percent Change From Baseline at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 42 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 48 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 42 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 48 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 42 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 48 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 42 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 48 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 42 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 48 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 42 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 48 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 42 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 48 months ] [ Designated as safety issue: No ]
    Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Not Provided
Not Provided
Not Provided
 
Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Low Bone Mineral Density
  • Drug: Placebo
    Placebo subcutaneous injection
  • Drug: Denosumab
    Denosumab for subcutaneous injection
    Other Names:
    • AMG 162
    • Prolia
  • Drug: Alendronate
    Alendronate 70 mg tablets
    Other Name: Fosamax
  • Placebo Comparator: Placebo
    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.
    Intervention: Drug: Placebo
  • Experimental: Denosumab 6 mg every 3 months
    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.
    Intervention: Drug: Denosumab
  • Experimental: Denosumab 14 mg every 3 months
    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.
    Intervention: Drug: Denosumab
  • Experimental: Denosumab 30 mg every 3 months
    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.
    Intervention: Drug: Denosumab
  • Experimental: Denosumab 14 mg every 6 months
    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.
    Intervention: Drug: Denosumab
  • Experimental: Denosumab 60 mg every 6 months
    Participants received denosumab 60 mg SC every 6 months until Month 42.
    Intervention: Drug: Denosumab
  • Experimental: Denosumab 100 mg every 6 months
    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.
    Intervention: Drug: Denosumab
  • Experimental: Denosumab 210 mg every 6 months
    Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42.
    Intervention: Drug: Denosumab
  • Active Comparator: Alendronate 70 mg
    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: Drug: Alendronate

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
412
June 2007
April 2007   (final data collection date for primary outcome measure)

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).
Female
up to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00043186
20010223
Not Provided
Amgen
Amgen
Not Provided
Study Director: MD Amgen
Amgen
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP