Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density
Condition: Low Bone Mineral Density
MeSH terms: Bone Diseases, Metabolic
Intervention: Placebo; Denosumab; Alendronate
Intervention description: Placebo subcutaneous injection; Denosumab for subcutaneous injection; Alendronate 70 mg tablets
Intervention MeSH terms: Denosumab; Alendronate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 412.0
Sex: Female
Maximum age: 80 Years
Healthy volunteers: No
Keywords: bone loss; osteoporosis

Summary:

      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.
    

Eligibility 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).