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
  Purpose

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.


Condition Intervention Phase
Low Bone Mineral Density
Drug: Placebo
Drug: Denosumab
Drug: Alendronate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 412
Study Start Date: May 2002
Study Completion Date: June 2007
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Placebo
Placebo subcutaneous injection
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.
Drug: Denosumab
Denosumab for subcutaneous injection
Other Names:
  • AMG 162
  • Prolia
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.
Drug: Denosumab
Denosumab for subcutaneous injection
Other Names:
  • AMG 162
  • Prolia
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.
Drug: Denosumab
Denosumab for subcutaneous injection
Other Names:
  • AMG 162
  • Prolia
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.
Drug: Denosumab
Denosumab for subcutaneous injection
Other Names:
  • AMG 162
  • Prolia
Experimental: Denosumab 60 mg every 6 months
Participants received denosumab 60 mg SC every 6 months until Month 42.
Drug: Denosumab
Denosumab for subcutaneous injection
Other Names:
  • AMG 162
  • Prolia
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.
Drug: Denosumab
Denosumab for subcutaneous injection
Other Names:
  • AMG 162
  • Prolia
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.
Drug: Denosumab
Denosumab for subcutaneous injection
Other Names:
  • AMG 162
  • Prolia
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.
Drug: Alendronate
Alendronate 70 mg tablets
Other Name: Fosamax

  Eligibility

Ages Eligible for Study:   up to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00043186

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00043186     History of Changes
Other Study ID Numbers: 20010223
Study First Received: August 6, 2002
Results First Received: December 22, 2009
Last Updated: September 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
bone loss
osteoporosis

Additional relevant MeSH terms:
Alendronate
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014