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

NCT ID: NCT00043186

Last Updated: 2013-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 412 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-05-31
• Study Completion Date: 2007-06-30

Brief 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.

Conditions

Low Bone Mineral Density

Keywords

bone loss; osteoporosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo subcutaneous injection

Denosumab 6 mg every 3 months

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.

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Denosumab for subcutaneous injection

Denosumab 14 mg every 3 months

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.

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Denosumab for subcutaneous injection

Denosumab 30 mg every 3 months

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.

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Denosumab for subcutaneous injection

Denosumab 14 mg every 6 months

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.

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Denosumab for subcutaneous injection

Denosumab 60 mg every 6 months

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

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Denosumab for subcutaneous injection

Denosumab 100 mg every 6 months

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.

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Denosumab for subcutaneous injection

Denosumab 210 mg every 6 months

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

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Denosumab for subcutaneous injection

Alendronate 70 mg

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.

Group Type: ACTIVE_COMPARATOR

Alendronate

Intervention Type: DRUG

Alendronate 70 mg tablets

Interventions

Placebo

Placebo subcutaneous injection

Intervention Type: DRUG

Denosumab

Denosumab for subcutaneous injection

Intervention Type: DRUG

Alendronate

Alendronate 70 mg tablets

Intervention Type: DRUG

Other Intervention Names

AMG 162; Prolia; Fosamax

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).

• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Countries

United States

References

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.2008.04.001. Epub 2008 May 20.

Reference Type: RESULT

PMID: 18495508 (View on PubMed)

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 Miner Res. 2007 Dec;22(12):1832-41. doi: 10.1359/jbmr.070809.

Reference Type: RESULT

PMID: 17708711 (View on PubMed)

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 low bone mineral density. N Engl J Med. 2006 Feb 23;354(8):821-31. doi: 10.1056/NEJMoa044459.

Reference Type: RESULT

PMID: 16495394 (View on PubMed)

Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008 Aug;43(2):222-229. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26.

Reference Type: RESULT

PMID: 18539106 (View on PubMed)

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.

Reference Type: RESULT

PMID: 19732857 (View on PubMed)

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20010223

Identifier Type: -

Identifier Source: org_study_id