Denosumab Adherence Preference Satisfaction Study

• Subject preference to treatment at the end of treatment period 2. [ Time Frame: Measured at the end of treatment period 2 (2 years) ] [ Designated as 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) ] [ Designated as safety issue: No ]
• BMQ scores and MARS scores during each treatment period. [ Time Frame: Measured during each treatment period ] [ Designated as safety issue: No ]
• Proportion of subjects adherent to treatment at the end of treatment period 2. [ Time Frame: Two year ] [ Designated as 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) ] [ Designated as 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) ] [ Designated as 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) ] [ Designated as 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) ] [ Designated as 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) ] [ Designated as safety issue: No ]

• Proportion of subjects adherent to treatment at the end of treatment period 2.
• Proportion of subjects compliant to treatment at the end of each treatment period.
• Proportion of subjects persisting with treatment at the end of each treatment period.
• Time to treatment non-adherence (weeks) with 70 mg alendronate QW in each treatment period.
• Time to treatment non-compliance (weeks) with 70 mg alendronate QW in each treatment period.
• Time to treatment non-persistence (weeks) with 70 mg alendronate QW in each treatment period.
• Subject preference to treatment at 18 months and at the end of treatment period 2.
• Proportion of subjects satisfied with treatment at the end of each treatment period.
• BMQ scores and MARS scores at six months and at teh end of each treatment period and changes in scores.

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).

• 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.

• 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).
  Interventions:

  • Drug: denosumab
  • Drug: alendronate
• 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).
  Interventions:

  • Drug: denosumab
  • Drug: alendronate

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).