A Randomized Study to Evaluate Safety and Efficacy of Transitioning Therapy From Alendronate to Denosumab (AMG 162) in Postmenopausal Women with Low Bone Mineral Density

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 500

Inclusion Criteria

Inclusion Criteria from Section 4.1 of the Protocol
4.1.1 = 55 years of age at the start of screening.

4.1.2 Ambulatory postmenopausal women based on medical history.
• Postmenopause will be defined as no vaginal bleeding or spotting for at least 12 months.
• If there is uncertainty regarding menopausal status, confirmation of serum FSH (= 50 mIU/mL) and serum estradiol (= 20 pg/mL) must be obtained.

4.1.3 Have received alendronate treatment at a dose of 70 mg/week or equivalent (ie, 10 mg/day) for at least the past 6 months prior to screening.

4.1.4 Screening BMD (g/cm2) values, at the lumbar spine OR total hip, that occur within the following ranges, based on the particular scanner that is used:
• GE Lunar Hologic
Lumbar spine 0.700 = BMD = 0.940 0.607= BMD = 0.827
Total hip 0.504 = BMD = 0.756 0.454 = BMD = 0.698
• Both the initial and the repeat DXA scan of the lumbar spine OR the total hip must meet the above eligibility criteria. At least 2 lumbar vertebrae must be evaluable by DXA.

4.1.5 At least one hip must be evaluable by DXA (eg, no history of either bilateral hip replacement or pins in both hips).

4.1.6 Provide the appropriate written informed consent before any study-specific procedure.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion Criteria from Section 4.2 of the Protocol

4.2.1 Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.

4.2.2 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 µIU/mL to 10.0 µIU/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 µIU/mL , subject is not eligible.
2. Current hyper- or hypoparathyroidism.
3. Elevated transaminases
• Serum aspartate aminotransferase (AST; serum glutamate-oxaloacetic transaminase [SGOT]) = 2.0 x upper limit of normal (ULN).
• Serum alanine aminotransferase (ALT; serum glutamate-pyruvate transaminase [SGPT]) = 2.0 x ULN.
4. Significantly impaired renal function as determined by a derived creatinine clearance (using the Cockroft-Gault formula) of = 35 mL/min calculated by the central laboratory.
5. Current hypo- or hypercalcemia based on the central laboratory reference ranges. 6. Active gastric or duodenal ulcer; or any history of significant gastrointestinal bleed requiring hospitalization or transfusion.
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 disorder that is associated with malabsorption.

4.2.3 Previous participation in clinical trials with denosumab.
4.2.4 Received any solid organ or bone marrow transplant.
4.2.5 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.
4.2.6 Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (< 49.9 nmol/L)]. Vitamin D repletion will be permitted and subjects may be re-screened; see Section 7.
4.2.7 Contraindicated or poorly tolerant of ALN therapy; contraindications for ALN therapy include:
a) Abnormalities of the esophagus, which delay esophageal emptying such as stricture or achalasia.
b) Inability to stand or sit upright for at least 30 minutes.
c) Hypersensitivity to ALN or other constituents of ALN tablets.
4.2.8 Known sensitivity to mammalian cell derived drug products.
4.2.9 Known intolerance to calcium supplements.
4.2.10 Administration of intravenous bisphosphonate, or fluoride (except for dental treatment) or strontium ranelate.
4.2.11 Administration of PTH or PTH derivatives (eg, teriparatide) within the last year.
4.2.12 Administration of any of the following treatments within 3 months of screening:
a) Any SERM (eg, raloxifene)
b) Tibolone
c) Anabolic steroids or testosterone
d) Glucocorticosteroids (

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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