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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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00729183
First received: August 4, 2008
Last updated: July 11, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Osteoporosis Drug: Odanacatib Drug: Placebo Drug: Vitamin D3 Drug: Calcium supplement Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Placebo-Controlled Study to Evaluate the Effect of Odanacatib (MK-0822) on Bone Mineral Density (BMD) and Overall Safety, and to Estimate the Effect of Odanacatib (MK-0822) on Bone Micro-architecture in Postmenopausal Women Treated With Vitamin D

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percent Change From Baseline to Month 12 in Lumbar Spine Areal Bone Mineral Density (aBMD) [ Time Frame: Baseline, 12 months ]
    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.

  • Percentage of Participants That Experienced an Adverse Event (AE) [ Time Frame: Up to ~14 days post study end (up to ~24 months) ]
    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.

  • Percentage of Participants That Discontinued Study Treatment Due to an AE [ Time Frame: Up to ~14 days post study end (up to ~24 months) ]
    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.


Secondary Outcome Measures:
  • Percent Change From Baseline to Month 24 in Lumbar Spine aBMD [ Time Frame: Baseline, 24 months ]
    aBMD (g/cm^2) was measured by DXA at the lumbar spine and mean BMD measurements from at least 3 evaluable vertebrae from L1 through 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 ANCOVA model, with percent change from baseline at Months 12 and 24 pre-specified to be reported as primary and secondary outcome measures, respectively.

  • Percent Change From Baseline in Total Hip aBMD [ Time Frame: Baseline, 12 months, 24 months ]
    aBMD (g/cm^2) data was measured by DXA at the total hip. All measurements utilized the same hip and at least 2 vertebrae for all time points. The left hip only was scanned. If the left hip was unevaluable, then the right hip was scanned. Once the appropriate leg was identified for scanning, it was used for all subsequent measurements. 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 total hip was assessed at the Screening visit (Baseline), Month 6, Month 12, and Month 24 for the repeated measures longitudinal ANCOVA model, with percent change from baseline at Months 12 and 24 pre-specified to be reported as secondary outcome measures.

  • Percent Change From Baseline in Femoral Neck aBMD [ Time Frame: Baseline, 12 months, 24 months ]
    aBMD (g/cm^2) data was measured by DXA at the femoral neck (hip). All measurements utilized the same hip and at least 2 vertebrae for all time points. The left hip only was scanned. If the left hip was unevaluable, then the right hip was scanned. Once the appropriate leg was identified for scanning, it was used for all subsequent measurements. 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 femoral neck was assessed at the Screening visit (Baseline), Month 6, Month 12, and Month 24 for the repeated measures longitudinal ANCOVA model, with percent change from baseline at Months 12 and 24 pre-specified to be reported as secondary outcome measures.

  • Percent Change From Baseline in Hip Trochanter aBMD [ Time Frame: Baseline, 12 months, 24 months ]
    aBMD (g/cm^2) data was measured by DXA at the hip trochanter. All measurements utilized the same hip and at least 2 vertebrae for all time points. The left hip only was scanned. If the left hip was unevaluable, then the right hip was scanned. Once the appropriate leg was identified for scanning, it was used for all subsequent measurements. 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 hip trochanter was assessed at the Screening visit (Baseline), Month 6, Month 12, and Month 24 for the repeated measures longitudinal ANCOVA model, with percent change from baseline at Months 12 and 24 pre-specified to be reported as secondary outcome measures.

  • Percent Change From Baseline in Total Radius aBMD [ Time Frame: Baseline, 12 months, 24 months ]
    aBMD (g/cm^2) data was measured by DXA at the total radius (forearm). 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 total radius was assessed at the Screening visit (Baseline), Month 6, Month 12, and Month 24 for the repeated measures longitudinal ANCOVA model, with percent change from baseline at Months 12 and 24 pre-specified to be reported as secondary outcome measures.

  • Percent Change From Baseline in Ultradistal Radius aBMD [ Time Frame: Baseline, 12 months, 24 months ]
    aBMD (g/cm^2) data was measured by DXA at the ultradistal radius (forearm). 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 ultradistal radius was assessed at the Screening visit (Baseline), Month 6, Month 12, and Month 24 for the repeated measures longitudinal ANCOVA model, with percent change from baseline at Months 12 and 24 pre-specified to be reported as secondary outcome measures.

  • Percent Change From Baseline in Distal Radius aBMD [ Time Frame: Baseline, 12 months, 24 months ]
    aBMD (g/cm^2) data was measured by DXA at the one-third distal radius (forearm). 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 distal radius was assessed at the Screening visit (Baseline), Month 6, Month 12, and Month 24 for the repeated measures longitudinal ANCOVA model, with percent change from baseline at Months 12 and 24 pre-specified to be reported as secondary outcome measures.

  • Percent Change From Baseline in Trabecular Volumetric Bone Mineral Density (vBMD) at Central Section of Spine (L1) [ Time Frame: Baseline, 12 months, 24 months ]
    Trabecular vBMD at the lumbar spine (L1) was measured by quantitative computed tomography (QCT). All QCT-derived vBMD measurements were evaluated centrally (and possibly locally) for bone and soft tissue abnormalities. Trabecular vBMD at the lumbar spine (L1) was assessed at the Screening visit (Baseline), Month 6, Month 12, and Month 24 for the repeated measures longitudinal ANCOVA model, with percent change from baseline at Months 12 and 24 pre-specified to be reported as secondary outcome measures.

  • Percent Change From Baseline in Trabecular vBMD at Central Section of Spine (L2) [ Time Frame: Baseline, 12 months, 24 months ]
    Trabecular vBMD at the lumbar spine (L2) was measured by quantitative computed tomography (QCT). All QCT-derived vBMD measurements were evaluated centrally (and possibly locally) for bone and soft tissue abnormalities. Trabecular vBMD at the lumbar spine (L2) was assessed at the Screening visit (Baseline), Month 6, Month 12, and Month 24 for the repeated measures longitudinal ANCOVA model, with percent change from baseline at Months 12 and 24 pre-specified to be reported as secondary outcome measures.

  • Percent Change From Baseline in Serum C-Terminal Telopeptides of Type 1 Collagen (s-CTx) Level [ Time Frame: Baseline, 12 months, 24 months ]
    s-CTx is a biochemical marker index of bone resorption. s-CTx was measured via fasting blood draws at Baseline (Randomization), Month 6, Month 12, Month 18, and Month 24 for the repeated measures longitudinal ANCOVA model, with percent change from baseline at Months 12 and 24 pre-specified to be reported as secondary outcome measures. S-CTx was analyzed using the log-transformed fraction from baseline using the per-protocol approach. Data were back-transformed for presentation and geometric LS mean percent change from baseline was reported with 95% CI.

  • Percent Change From Baseline in Serum N-Terminal Propeptides of Type 1 Collagen (s-P1NP) Level [ Time Frame: Baseline, 12 months, 24 months ]
    s-P1NP is a biochemical marker index of bone formation. s-P1NP was measured via fasting blood draws at Baseline (Randomization), Month 6, Month 12, Month 18, and Month 24 for the repeated measures longitudinal ANCOVA model, with percent change from baseline at Months 12 and 24 pre-specified to be reported as secondary outcome measures. s-P1NP was analyzed using the log-transformed fraction from baseline using the per-protocol approach. Data were back-transformed for presentation and geometric LS mean percent change from baseline was reported with 95% CI.


Enrollment: 214
Study Start Date: October 2008
Study Completion Date: March 2011
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Odanacatib 50 mg
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
Odanacatib 50 mg tablets, taken orally once weekly for 24 months.
Other Name: MK-0822
Drug: Vitamin D3
Vitamin D3 tablets (5600 IU) taken orally once weekly for 24 months.
Drug: Calcium supplement
Calcium supplement 500 mg tablet taken orally once daily (up to ~1200 mg total) for 24 months.
Other Names:
  • calcium carbonate
  • calcium citrate
Placebo Comparator: Placebo
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
Matching placebo tablets to odanacatib taken orally once weekly for 24 months.
Drug: Vitamin D3
Vitamin D3 tablets (5600 IU) taken orally once weekly for 24 months.
Drug: Calcium supplement
Calcium supplement 500 mg tablet taken orally once daily (up to ~1200 mg total) for 24 months.
Other Names:
  • calcium carbonate
  • calcium citrate

  Eligibility

Ages Eligible for Study:   45 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00729183

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00729183     History of Changes
Other Study ID Numbers: 0822-031
2008_539 ( Other Identifier: Merck Registration Number )
Study First Received: August 4, 2008
Results First Received: April 13, 2017
Last Updated: July 11, 2017

Additional relevant MeSH terms:
Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Calcium, Dietary
Calcium Carbonate
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Antacids
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents

ClinicalTrials.gov processed this record on September 21, 2017