Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density

Amgen

Status and phase: Completed; Phase 2

Conditions: Low Bone Mineral Density

Treatments: Drug: Denosumab; Drug: Placebo; Drug: Alendronate

Study type: Interventional

Funder types: Industry

Identifiers

NCT00043186

20010223

Details and patient eligibility

About

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.

Enrollment: 412 patients

Sex: Female

Ages: Under 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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412 participants in 9 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42.

Treatment:

Drug: Placebo

Denosumab 6 mg every 3 months

Experimental group

Description:

Participants received denosumab 6 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.

Treatment:

Drug: Denosumab

Denosumab 14 mg every 3 months

Experimental group

Description:

Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.

Treatment:

Drug: Denosumab

Denosumab 30 mg every 3 months

Experimental group

Description:

Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42.

Treatment:

Drug: Denosumab

Denosumab 14 mg every 6 months

Experimental group

Description:

Participants received denosumab 14 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.

Treatment:

Drug: Denosumab

Denosumab 60 mg every 6 months

Experimental group

Description:

Participants received denosumab 60 mg SC every 6 months until Month 42.

Treatment:

Drug: Denosumab

Denosumab 100 mg every 6 months

Experimental group

Description:

Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.

Treatment:

Drug: Denosumab

Denosumab 210 mg every 6 months

Experimental group

Description:

Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42.

Treatment:

Drug: Denosumab

Alendronate 70 mg

Active Comparator group

Description:

Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.

Treatment:

Drug: Alendronate