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

NCT00043186 | Completed Phase 2 Results

• 1 other identifier: 20010223
• Study Type: interventional
• Target: 412
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (35)

• Serum CTX Percent Change From Baseline at Month 12

  Baseline and Month 12

• Urine NTX/Creatinine Percent Change From Baseline at Month 12

  Baseline and Month 12

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

  Baseline and Month 12

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

  Baseline and 24 months

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

  Baseline and 36 months

Study Arms (9)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Denosumab 6 mg every 3 months

EXPERIMENTAL

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.

Drug: Denosumab

Denosumab 14 mg every 3 months

EXPERIMENTAL

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.

Drug: Denosumab

Denosumab 30 mg every 3 months

EXPERIMENTAL

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.

Drug: Denosumab

Denosumab 14 mg every 6 months

EXPERIMENTAL

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.

Drug: Denosumab

Denosumab 60 mg every 6 months

EXPERIMENTAL

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

Drug: Denosumab

Denosumab 100 mg every 6 months

EXPERIMENTAL

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.

Drug: Denosumab

Denosumab 210 mg every 6 months

EXPERIMENTAL

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

Drug: Denosumab

Alendronate 70 mg

ACTIVE COMPARATOR

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.

Drug: Alendronate

Interventions

Placebo DRUG

Placebo subcutaneous injection

Placebo

Denosumab DRUG

Denosumab for subcutaneous injection

Also known as: AMG 162, Prolia

Denosumab 100 mg every 6 months; Denosumab 14 mg every 3 months; Denosumab 14 mg every 6 months; Denosumab 210 mg every 6 months; Denosumab 30 mg every 3 months; Denosumab 6 mg every 3 months; Denosumab 60 mg every 6 months

Alendronate DRUG

Alendronate 70 mg tablets

Also known as: Fosamax

Alendronate 70 mg

Eligibility Criteria

• Age: Up to 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Related 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.2008.04.001. Epub 2008 May 20.

  PMID: 18495508 RESULT

• 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.

  PMID: 17708711 RESULT

• 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.

  PMID: 16495394 RESULT

• 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.

  PMID: 18539106 RESULT

• 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.

  PMID: 19732857 RESULT

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Bone Diseases, Metabolic; Osteoporosis

Interventions

Denosumab; Alendronate

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2002
• First Posted: August 7, 2002
• Study Start: May 1, 2002
• Primary Completion: April 1, 2007
• Study Completion: June 1, 2007
• Last Updated: September 18, 2013
• Results First Posted: July 28, 2010

Record last verified: 2013-09