Official Title: “A Multicenter, Randomized, Cross-Over, Open-Label Study to Evaluate the Adherence, Preference, and Satisfaction of Denosumab and Alendronate in Postmenopausal Women With Low Bone Mineral Density”

The primary objective is to evaluate the adherence of subjects to SC 60 mg denosumab Q6M treatment compared to oral 70 mg alendronate QW treatment at the end of treatment period 1 (12 months).

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2010

Intervention(s) in this Clinical Trial

• Drug: denosumab
  • Subjects will receive 60 mg of denosumab Q6M SC for 1 year. If a subject is randomized to Treatment Sequence A they will receive denosumab for 1 year in Treatment Period 2. If a subject is randomized to Treatment Sequence B they will receive denosumab for 1 year in Treatment Period 1.
• Drug: alendronate
  • Subjects will take 70 mg QW of oral alendronate for 1 year. If a subject is randomized to Treatment Sequence A they will receive alendronate for 1 year in Treatment Period 2. If a subject is randomized to Treatment Sequence B they will receive alendronate for 1 year in Treatment Period 1.

Arms, Groups and Cohorts in this Clinical Trial

• Other: Treatment Sequence B
  • When a subject meets all eligibility criteria and signs the informed consent, they will be randomized in a 1:1 allocation to one of the two treatment Sequences. Subjects randomized to treatment sequence B will receive 70 mg oral alendronate QW for 1-year (Treatment period 1) followed by denosumab 60 mg Q6M SC for 1 year (Treatment Period 2).
• Other: Treatment Sequence A
  • When a subject meets all eligibility criteria and signs the informed consent, they will be randomized in a 1:1 allocation to one of the two treatment sequences. Subjects randomized to treatment sequence A will receive 60 mg denosumab Q6M SC for 1-year (Treatment period 1) followed by oral alendronate 70 mg QW for 1 year (Treatment period 2).

Primary Measures

• Proportion of subjects adherent to treatment at the end of treatment period 1.
  • Time Frame: One year
    Safety Issue?: No

Secondary Measures

• Proportion of subjects adherent to treatment at the end of treatment period 2.
  • Time Frame: Two year
    Safety Issue?: No
• Proportion of subjects compliant to treatment at the end of each treatment period.
  • Time Frame: Measured at the end of each treatment period (1 year & 2 years)
    Safety Issue?: No
• Proportion of subjects persisting with treatment at the end of each treatment period.
  • Time Frame: Measured at the end of each treatment period (1 year & 2 years)
    Safety Issue?: No
• Time to treatment non-adherence (weeks) with 70 mg alendronate QW in each treatment period.
  • Time Frame: Measured at the end of each treatment period (1 year & 2 years)
    Safety Issue?: No
• Time to treatment non-compliance (weeks) with 70 mg alendronate QW in each treatment period.
  • Time Frame: Measured at the end of each treatment period (1 year & 2 years)
    Safety Issue?: No
• Time to treatment non-persistence (weeks) with 70 mg alendronate QW in each treatment period.
  • Time Frame: Measured at the end of each treatment period (1 year & 2 years)
    Safety Issue?: No
• Subject preference to treatment at the end of treatment period 2.
  • Time Frame: Measured at the end of treatment period 2 (2 years)
    Safety Issue?: No
• Proportion of subjects satisfied with treatment at the end of each treatment period.
  • Time Frame: Measured at the end of each treatment period (1 year & 2 years)
    Safety Issue?: No
• BMQ scores and MARS scores during each treatment period.
  • Time Frame: Measured during each treatment period
    Safety Issue?: No

Inclusion Criteria:

• Ambulatory postmenopausal women based on medical history
• > or = 55 years of age at the start of screening
• Screening BMD values (g/cm²), at the lumbar spine OR femoral neck OR total hip that occur within the specified ranges based on the particular scanner that is used. At least 2 lumbar vertebrae must be evaluable by DXA, or at least one hip must be evaluable by DXA
• Provide written informed consent before any study specific procedure is performed.

Exclusion Criteria:

• Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
• Hyper- or hypothyroidism; however, stable subjects, in the investigator's opinion, on thyroid hormone replacement therapy are allowed
• Current hyper- or hypoparathyroidism
• Current hypo- or hyper calcemia based on the central laboratory reference ranges for albumin-adjusted serum calcium
• Rheumatoid arthritis, Paget's disease, Cushing's disease, hyperprolactinemia, or cirrhosis of the liver
• Any metabolic bone disease, e.g. osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings
• Any symptomatic vertebral fracture within 3 months prior to screening
• Previous participation in clinical trials with denosumab
• Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (<49.9nmol/L)]
• Contraindicated to alendronate therapy; contraindications for alendronate 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.
• Any known prior bisphosphonate use
• Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trail (s), or subject is receiving other investigational agent(s).

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 55 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Amgen

Overall Clinical Trial Officials and Contacts

MD Study Director Amgen  

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00518531

Study ID Number: 20060232

ClinicalTrials.gov Identifier: NCT00518531

Health Authority: Canada: Health Canada

AmgenTrials clinical trials website