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

Low Bone Mineral Density Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of AMG 162 in the Treatment of Postmenopausal Women With Low Bone Mineral Density

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00043186
• Other study ID #: 20010223
• Status: Completed
• Phase: Phase 2
• First received: August 6, 2002
• Last updated: September 6, 2013
• Start date: May 2002
• Est. completion date: June 2007

Study information

• Verified date: September 2013
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 412
• Est. completion date: June 2007
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A to 80 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Low Bone Mineral Density

Intervention

Drug:
• Placebo
Placebo subcutaneous injection
• Denosumab
Denosumab for subcutaneous injection
• Alendronate
Alendronate 70 mg tablets

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (5)

Beck TJ, Lewiecki EM, Miller PD, Felsenberg D, Liu Y, Ding B, Libanati C. Effects of denosumab on the geometry of the proximal femur in postmenopausal women in comparison with alendronate. J Clin Densitom. 2008 Jul-Sep;11(3):351-9. doi: 10.1016/j.jocd.200 — View Citation

Lewiecki EM, Miller PD, McClung MR, Cohen SB, Bolognese MA, Liu Y, Wang A, Siddhanti S, Fitzpatrick LA; AMG 162 Bone Loss Study Group. Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone M — View Citation

McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ; AMG 162 Bone Loss Study Group. Denosumab in postmenopausal women with — View Citation

Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J; Amg Bone Loss Study Group. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and re — View Citation

Peterson MC, Riggs MM. A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling. Bone. 2010 Jan;46(1):49-63. doi: 10.1016/j.bone.2009.08.053. Epub 2009 Sep 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline and Month 12	No
Secondary	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.	Baseline and Month 12	No
Secondary	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.	Baseline and Month 12	No
Secondary	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.	Baseline and Month 12	No
Secondary	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.	Baseline and 24 months	No
Secondary	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.	Baseline and 36 months	No
Secondary	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.	Baseline and 42 months	No
Secondary	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.	Baseline and 48 months	No
Secondary	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.	Baseline and 24 months	No
Secondary	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.	Baseline and 36 months	No
Secondary	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.	Baseline and 42 months	No
Secondary	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.	Baseline and 48 months	No
Secondary	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.	Baseline and 24 months	No
Secondary	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.	Baseline and 36 months	No
Secondary	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.	Baseline and 42 months	No
Secondary	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.	Baseline and 48 months	No
Secondary	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.	Baseline and 12 months	No
Secondary	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.	Baseline and 24 months	No
Secondary	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.	Baseline and 36 months	No
Secondary	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.	Baseline and 42 months	No
Secondary	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.	Baseline and 48 months	No
Secondary	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.	Baseline and 12 months	No
Secondary	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.	Baseline and 24 months	No
Secondary	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.	Baseline and 36 months	No
Secondary	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.	Baseline and 42 months	No
Secondary	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.	Baseline and 48 months	No
Secondary	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.	Baseline and 12 months	No
Secondary	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.	Baseline and 24 months	No
Secondary	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.	Baseline and 36 months	No
Secondary	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.	Baseline and 42 months	No
Secondary	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.	Baseline and 48 months	No
Secondary	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.	Baseline and 12 months	No
Secondary	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.	Baseline and 24 months	No
Secondary	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.	Baseline and 36 months	No
Secondary	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.	Baseline and 42 months	No
Secondary	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.	Baseline and 48 months	No

External Links

•   AmgenTrials clinical trials website