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

Amgen412 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

412

Conditions

Low Bone Mineral Density

Interventions

PlaceboDRUG

Placebo subcutaneous injection

DenosumabDRUG

Denosumab for subcutaneous injection

AlendronateDRUG

Alendronate 70 mg tablets

Eligibility

Sex: FEMALEMax age: 80 Years

Medical Language ↔ Plain English

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).

Outcomes

Primary Outcomes

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and Month 12

Secondary Outcomes

Serum CTX Percent Change From Baseline at Month 12

Serum C-Telopeptide (CTX). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and Month 12

Urine NTX/Creatinine Percent Change From Baseline at Month 12

Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and Month 12

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and Month 12

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Data from ClinicalTrials.gov

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Time frame: Baseline and 36 months

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months

Serum CTX Percent Change From Baseline at Month 24

Serum C-Telopeptide (CTX). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Serum CTX Percent Change From Baseline at Month 36

Serum C-Telopeptide (CTX). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 36 months

Serum CTX Percent Change From Baseline at Month 42

Serum C-Telopeptide (CTX). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Serum CTX Percent Change From Baseline at Month 48

Serum C-Telopeptide (CTX). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months

Urine NTX/Creatinine Percent Change From Baseline at Month 24

Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Urine NTX/Creatinine Percent Change From Baseline at Month 36

Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 36 months

Urine NTX/Creatinine Percent Change From Baseline at Month 42

Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Urine NTX/Creatinine Percent Change From Baseline at Month 48

Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months

Total Hip Bone Mineral Density Percent Change From Baseline at Month 12

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 12 months

Total Hip Bone Mineral Density Percent Change From Baseline at Month 24

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Total Hip Bone Mineral Density Percent Change From Baseline at Month 36

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 36 months

Total Hip Bone Mineral Density Percent Change From Baseline at Month 42

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Total Hip Bone Mineral Density Percent Change From Baseline at Month 48

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 12 months

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 36 months

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months

Total Body Bone Mineral Density Percent Change From Baseline at Month 12

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 12 months

Total Body Bone Mineral Density Percent Change From Baseline at Month 24

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Total Body Bone Mineral Density Percent Change From Baseline at Month 36

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 36 months

Total Body Bone Mineral Density Percent Change From Baseline at Month 42

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Total Body Bone Mineral Density Percent Change From Baseline at Month 48

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12

Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 12 months

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24

Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36

Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 36 months

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42

Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48

Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months