Study to Evaluate Efficacy of Odanacatib (MK-0822) on Bone Mineral Density (BMD) and Bone Micro-architecture and Overall Safety in Postmenopausal Women (MK-0822-031)

NCT00729183 | Completed Phase 3 Results

• 2 other identifiers: 0822-0312008_539
• Study Type: interventional
• Target: 214
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will evaluate the safety and treatment effect of 50 mg odanacatib (MK-0822) with Vitamin D versus placebo with Vitamin D in postmenopausal women with low bone density. The primary efficacy hypothesis is that odanacatib will increase aBMD at the lumbar spine compared to placebo at 12 months.

Conditions

Osteoporosis

Outcome Measures

Primary Outcomes (3)

• Percent Change From Baseline to Month 12 in Lumbar Spine Areal Bone Mineral Density (aBMD)

  aBMD (g/cm\^2) was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and mean BMD measurements from at least 3 evaluable lumbar spine vertebrae (L1-L4) were used. If a vertebra was fractured at baseline or became fractured during the study, its BMD measurement was excluded from the analysis and the lumbar spine BMD was recalculated based on the three remaining vertebrae. aBMD data was centrally evaluated and all areal BMD measurements included a longitudinal BMD correction factor as determined by the quality control center. aBMD at the lumbar spine was assessed at the Screening visit (Baseline), Month 6, Month 12, and Month 24 for the repeated measures longitudinal Analysis of Covariates (ANCOVA) model, with percent change from baseline at Months 12 and 24 pre-specified to be reported as primary and secondary outcome measures, respectively.

  Baseline, 12 months

• Percentage of Participants That Experienced an Adverse Event (AE)

  An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's products, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product was also an AE. The percentage of participants that experienced at least one AE was reported for each treatment arm.

  Up to ~14 days post study end (up to ~24 months)

• Percentage of Participants That Discontinued Study Treatment Due to an AE

  An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's products, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product was also an AE. The percentage of participants that discontinued study treatment (different from discontinuation of the study) due to an AE was reported for each treatment arm.

  Up to ~14 days post study end (up to ~24 months)

Secondary Outcomes (11)

• Percent Change From Baseline to Month 24 in Lumbar Spine aBMD

  Baseline, 24 months

• Percent Change From Baseline in Total Hip aBMD

  Baseline, 12 months, 24 months

• Percent Change From Baseline in Femoral Neck aBMD

  Baseline, 12 months, 24 months

• Percent Change From Baseline in Hip Trochanter aBMD

  Baseline, 12 months, 24 months

• Percent Change From Baseline in Total Radius aBMD

  Baseline, 12 months, 24 months

Study Arms (2)

Odanacatib 50 mg

EXPERIMENTAL

Participants receive 50 mg odanacatib and open-label 5600 IU vitamin D3 tablets once weekly for 24 months. Participants also receive 500 mg of open-label daily calcium supplement as needed to ensure a total daily calcium intake of 1200 mg.

Drug: Odanacatib; Drug: Vitamin D3; Drug: Calcium supplement

Placebo

PLACEBO COMPARATOR

Participants receive matching placebo to odanacatib and open-label 5600 IU vitamin D3 once weekly for 24 months. Participants also receive 500 mg of open-label daily calcium supplement as needed to ensure a total daily calcium intake of 1200 mg.

Drug: Placebo; Drug: Vitamin D3; Drug: Calcium supplement

Interventions

Odanacatib DRUG

Odanacatib 50 mg tablets, taken orally once weekly for 24 months.

Also known as: MK-0822

Odanacatib 50 mg

Placebo DRUG

Matching placebo tablets to odanacatib taken orally once weekly for 24 months.

Placebo

Vitamin D3 DRUG

Vitamin D3 tablets (5600 IU) taken orally once weekly for 24 months.

Odanacatib 50 mg; Placebo

Calcium supplement DRUG

Calcium supplement 500 mg tablet taken orally once daily (up to \~1200 mg total) for 24 months.

Also known as: calcium carbonate, calcium citrate

Odanacatib 50 mg; Placebo

Eligibility Criteria

• Age: 45 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has been postmenopausal for 3 years
• Participant has BMD t-score at the total hip, hip trochanter, femoral neck, or lumbar spine ≥ -1.5 but \> -3.5
• Participant has 2 hips that are evaluable by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), e.g. contain no hardware from orthopedic procedures
• Participant is ambulatory

You may not qualify if:

• Participant has had a previous hip fracture
• Participant has had \>1 prior clinical vertebral fracture AND is a candidate for osteoporosis therapy
• Participant has been treated with oral bisphosphonates, strontium, parathyroid hormone (PTH) or other agents with an effect on bone
• Participant has had metabolic bone disorder other than osteoporosis
• Participant has renal stones, Parkinson's disease, multiple sclerosis (MS) or active parathyroid disease.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• Engelke K, Fuerst T, Dardzinski B, Kornak J, Ather S, Genant HK, de Papp A. Odanacatib treatment affects trabecular and cortical bone in the femur of postmenopausal women: results of a two-year placebo-controlled trial. J Bone Miner Res. 2015 Jan;30(1):30-8. doi: 10.1002/jbmr.2292.

  PMID: 24898537 DERIVED

• Brixen K, Chapurlat R, Cheung AM, Keaveny TM, Fuerst T, Engelke K, Recker R, Dardzinski B, Verbruggen N, Ather S, Rosenberg E, de Papp AE. Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trial. J Clin Endocrinol Metab. 2013 Feb;98(2):571-80. doi: 10.1210/jc.2012-2972. Epub 2013 Jan 21.

  PMID: 23337728 DERIVED

MeSH Terms

Conditions

Osteoporosis

Interventions

odanacatib; Cholecalciferol; Calcium Carbonate; Calcium Citrate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals; Citric Acid; Citrates; Tricarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2008
• First Posted: August 7, 2008
• Study Start: October 2, 2008
• Primary Completion: March 23, 2010
• Study Completion: March 21, 2011
• Last Updated: August 27, 2018
• Results First Posted: May 16, 2017

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share