A Randomized, Double-Blind Study to Compare the Efficacy of Treatment With Denosumab Versus Alendronate Sodium in Postmenopausal Women With Low Bone Mineral Density.

This study has been completed.
Sponsor:
Information provided by:
Amgen
ClinicalTrials.gov Identifier:
NCT00330460
First received: April 6, 2006
Last updated: January 20, 2011
Last verified: January 2011
  Purpose

The purpose of this study is to determine whether in postmenopausal women with low bone mineral density, the mean percent change in total hip BMD in subjects receiving denosumab is not less than that observed in subjects receiving alendronate sodium by more than a pre-specified non-inferiority margin.


Condition Intervention Phase
Osteoporosis
Osteopenia
Drug: Alendronate
Drug: Denosumab
Phase 3

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 Study to Compare the Efficacy of Treatment With Denosumab Versus Alendronate Sodium in Postmenopausal Women With Low Bone Mineral Denisty

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Total Hip Bone Mineral Density Percent Change From Baseline at Month 12 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.


Secondary Outcome Measures:
  • Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

  • Trochanter Bone Mineral Density Percent Change From Baseline at Month 12 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

  • Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 12 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

  • Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.


Enrollment: 1189
Study Start Date: May 2006
Study Completion Date: January 2008
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Alendronate
Subjects in this arm will receive active ALN and placebo denosumab
Drug: Alendronate
ALN; 70 mg; oral; once weekly
Experimental: Denosumab
Subjects in this arm will receive active denosumab and placbo ALN
Drug: Denosumab
60 mg; SC; every 6 months

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: - Patient is an ambulatory postmenopausal woman - Patient has BMD value that corresponds to a T-score of less than or equal to -2.0 (g/cm2) at the lumbar spine OR total hip within range specific to the study protocol. Exclusion Criteria: o Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures

  • Evidence of any of the following per subject report, chart review or central laboratory result:

    1. Hyper- or hypothyroidism; however, subjects on stable thyroid hormone replacement therapy may be allowed per the following criteria:

      • If TSH level is normal, subject is eligible for the study.
      • If TSH level is below normal range, subject is not eligible for the study.
      • If TSH level is elevated (> 5.5 mIU/mL to 10.0 mIU/mL), serum T4 should be measured. If serum T4 is within normal range, subject is eligible. If serum T4 is outside of normal range, subject is not eligible for the study.
      • If TSH level is above 10.0 mIU/mL, subject is not eligible.
    2. Current hyper- or hypoparathyroidism
    3. Elevated transaminases

      • Serum aspartate aminotransferase (AST; serum glutamate-oxaloacetic transaminase [SGOT]) ³ 2.0 x upper limits of normal (ULN)
      • Serum alanine aminotransferase (ALT; serum glutamate-pyruvate transaminase [SGPT]) ³ 2.0 x ULN
    4. Significantly impaired renal function as determined by serum creatinine ³ 2.0 mg/dL
    5. Current hypo- or hypercalcemia based on the central laboratory reference ranges
    6. Active gastric or duodenal ulcer; history of significant gastrointestinal bleed requiring hospitalization or transfusion, or dyspepsia or gastroesophageal reflux disease that is uncontrolled by medication
    7. Rheumatoid Arthritis, Paget's disease, Cushing's disease, hyperprolactinemia, or cirrhosis of the liver
    8. Known to have tested positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen
    9. Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years
    10. Any metabolic bone disease, eg, osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings
    11. Malabsorption syndrome or any gastrointestinal disorders that are associated with malabsorption
  • Received any solid organ or bone marrow transplant
  • Vitamin D deficiency (25(OH) vitamin D level < 12 ng/mL). Vitamin D repletion will be permitted and subjects may be re-screened; see Section 7.
  • Any laboratory abnormality which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results
  • Contraindicated or poorly tolerant of ALN therapy; contraindications for ALN therapy include:

    1. Abnormalities of the esophagus, which delay esophageal emptying such as stricture or achalasia.
    2. Inability to stand or sit upright for at least 30 minutes.
    3. Hypersensitivity to ALN or other constituents of ALN tablets o Known sensitivity to mammalian cell derived drug products
  • Known intolerance to calcium supplements
  • Administration of intravenous bisphosphonate, or fluoride (except for dental treatment) or strontium ranelate
  • Oral bisphosphonate treatment:

    • ³ 3 months cumulatively in the past 2 years, OR
    • ³ 1 month in the past year, OR
    • Any use during the 3-month period prior to randomization
  • PTH or PTH derivatives (eg, teriparatide) within the last year
  • Administration of any of the following treatments within 3 months of randomization:

    1. Any SERM (eg, raloxifene)
    2. Tibolone
    3. Anabolic steroids or testosterone
    4. Glucocorticosteroids (³ 5 mg prednisone equivalent per day for more than 10 days)
    5. Systemic (oral, transdermal, topical) hormone replacement therapy (local vaginal estrogen preparation will be allowed)
    6. Calcitonin
    7. Calcitriol or vitamin D derivatives
    8. Other bone active drugs including anti-convulsives (except benzodiazepines) and heparin
    9. Chronic systemic ketoconazole, androgens, ACTH, cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone agonists
    10. Height, weight or girth which may preclude accurate DXA measurements
  • Less than 2 lumbar vertebrae (L1-L4) evaluable for DXA measurements
  • Both hips not evaluable by DXA (eg, history of bilateral hip replacement or pins in both hips)
  • Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s)
  • Any physical or psychiatric disorder which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results
  • Evidence of alcohol or substance-abuse within the last 12 months which the investigator believes would interfere with understanding or completing the study
  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: NCT00330460

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

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Global Development Leader, Amgen Inc.
ClinicalTrials.gov Identifier: NCT00330460     History of Changes
Other Study ID Numbers: 20050141
Study First Received: April 6, 2006
Results First Received: June 18, 2010
Last Updated: January 20, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
Osteoporosis
Osteopenia
AMG 162
Fracture - hip
Postmenopausal

Additional relevant MeSH terms:
Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Alendronate
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014