Efficacy and Safety of Odanacatib (MK-0822) in Participants With Involutional Osteoporosis (MK-0822-022)

NCT00620113 | Completed Phase 2 Results

• 3 other identifiers: 0822-022MK-0822-0222007_034
• Study Type: interventional
• Target: 287
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to assess the dose-response on the percent change from baseline in lumbar spine bone mineral density (BMD) at lumbar vertebrae 1 to 4 (L1- L4) when odanacatib (MK-0822) 10 mg, 25 mg, 50 mg or placebo is orally administered once weekly for 52 weeks to Japanese involutional osteoporosis participants. The study will also assess safety and tolerability of odanacatib (10, 25, and 50 mg) in these participants. The study will enroll approximately 280 participants and randomly assign them to 3 different doses of odanacatib or placebo for 52 weeks, along with supplemental vitamin D3 and calcium carbonate. The primary efficacy hypothesis is that a dose-response relationship on the percent change from baseline in lumbar spine BMD (L1- L4) is seen when odanacatib 10, 25, 50 mg or placebo is orally administered once weekly for 52 weeks to involutional osteoporosis participants. The primary safety hypothesis is that odanacatib will be safe and well tolerated over 52 weeks to involutional osteoporosis participants.

Conditions

Osteoporosis Postmenopausal

Outcome Measures

Primary Outcomes (3)

• Percent Change From Baseline to Week 52 in Lumbar Spine Bone Mineral Density (BMD) at Lumbar Vertebrae 1 to 4 (L1-L4)

  BMD (g/cm2) data was measured by dual-energy X-ray absorptiometry (DXA) at lumbar spine vertebrae 1 through 4 (L1-L4) from anterior view at the Observation visit (up to 5 weeks before Treatment Period), Week 0 (start of Treatment Period) and Week 52 (end of Treatment Period) or at discontinuation. Baseline was defined as the average of the 2 values collected at the Observation visit and Week 0 visit. Percent change from baseline in BMD = (\[BMD at Week 52 visit\] - \[baseline BMD\] ÷ baseline BMD) × 100. Measurements were performed using the Hologic Quantitative Digital Radiography (QDR) Series densitometer, and by same machine and under same scan mode throughout the study period. BMD data was centrally judged.

  Baseline (Observation visit to Wk 0 treatment visit), Week 52

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

  An AE was defined as any unfavorable and unintended change in the structure (sign), function (symptoms), or chemistry of the body (laboratory data) temporally associated with the use of the SPONSOR's products (including placebo), 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 number of participants that experienced at least one AE was reported for each treatment arm.

  From first dose up to Post-Study (up to 54 weeks)

• Number of Participants That Discontinued Study Drug Due to an AE

  An AE was defined as any unfavorable and unintended change in the structure (sign), function (symptoms), or chemistry of the body (laboratory data) temporally associated with the use of the SPONSOR's products (including placebo), 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 number of participants that discontinued study drug due to an AE was reported for each treatment arm. Participants may have discontinued study drug but continued on the trial.

  From first dose up to end of treatment (up to 52 weeks)

Secondary Outcomes (8)

• Percent Change From Baseline to Week 52 in Total Hip BMD

  Baseline (Observation visit to Wk 0 treatment visit), Week 52

• Percent Change From Baseline to Week 52 in Femoral Neck BMD

  Baseline (Observation visit to Wk 0 treatment visit), Week 52

• Percent Change From Baseline to Week 52 in Trochanter BMD

  Baseline (Observation visit to Wk 0 treatment visit), Week 52

• Percent Change From Baseline to Week 52 in Urinary N-telopeptides/Creatinine (u-NTx/Cre) Ratio

  Baseline (Wk 0), Week 52

• Percent Change From Baseline to Week 52 in Serum C-Telopeptides of Type 1 Collagen (s-CTx) Level

  Baseline (Wk 0), Week 52

Study Arms (4)

Placebo

PLACEBO COMPARATOR

After an observation period of \~5 weeks, participants receive dose-matched placebo to odanacatib once weekly for 52 weeks. Participants also receive weekly supplementation with open-label 5600 International Units (IU) vitamin D3 and 500 mg of open-label daily calcium supplement (if calcium \<1000 mg per day from dietary and other sources) throughout the observation and treatment periods.

Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium carbonate; Drug: Placebo

Odanacatib 10 mg

EXPERIMENTAL

After an observation period of \~5 weeks, participants receive 10 mg odanacatib once weekly for 52 weeks. Participants also receive weekly supplementation with open-label 5600 IU vitamin D3 and 500 mg of open-label daily calcium supplement (if calcium \<1000 mg per day from dietary and other sources) throughout the observation and treatment periods.

Drug: Odanacatib; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium carbonate

Odanacatib 25 mg

EXPERIMENTAL

After an observation period of \~5 weeks, participants receive 25 mg odanacatib once weekly for 52 weeks. Participants also receive weekly supplementation with open-label 5600 IU vitamin D3 and 500 mg of open-label daily calcium supplement (if calcium \<1000 mg per day from dietary and other sources) throughout the observation and treatment periods.

Drug: Odanacatib; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium carbonate

Odanacatib 50 mg

PLACEBO COMPARATOR

After an observation period of \~5 weeks, participants receive 50 mg odanacatib once weekly for 52 weeks. Participants also receive weekly supplementation with open-label 5600 IU vitamin D3 and 500 mg of open-label daily calcium supplement (if calcium \<1000 mg per day from dietary and other sources) throughout the observation and treatment periods.

Drug: Odanacatib; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium carbonate

Interventions

Odanacatib DRUG

Odanacatib tablets 10 mg, 25 mg, or 50 mg (depending upon randomization), taken orally once weekly for 52 weeks.

Also known as: MK-0822

Odanacatib 10 mg; Odanacatib 25 mg; Odanacatib 50 mg

Vitamin D3 DIETARY_SUPPLEMENT

Two Vitamin D3 tablets (5600 IU total) taken orally once weekly for 52 weeks.

Also known as: cholecalciferol

Odanacatib 10 mg; Odanacatib 25 mg; Odanacatib 50 mg; Placebo

Calcium carbonate DIETARY_SUPPLEMENT

Calcium carbonate 500 mg tablet taken orally every day for 52 weeks.

Odanacatib 10 mg; Odanacatib 25 mg; Odanacatib 50 mg; Placebo

Placebo DRUG

Dose-matched placebo tablets to odanacatib, taken orally once weekly for 52 weeks.

Placebo

Eligibility Criteria

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

You may qualify if:

• Postmenopausal woman (for at least 5 years) or men who are aged between 45 to 85
• Participant who has low bone mineral density
• Participant has anatomy suitable for dual-energy x-ray absorptiometry (DXA) of the lumber spine and hip
• Participant is ambulatory (can walk)

You may not qualify if:

• Participant has secondary osteoporosis or has a metabolic bone disorder other than osteoporosis or osteopenia
• Participant has received osteoporosis medications or other medications that affect bone
• Participant is already participating in another drug study

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Nakamura T, Shiraki M, Fukunaga M, Tomomitsu T, Santora AC, Tsai R, Fujimoto G, Nakagomi M, Tsubouchi H, Rosenberg E, Uchida S. Effect of the cathepsin K inhibitor odanacatib administered once weekly on bone mineral density in Japanese patients with osteoporosis--a double-blind, randomized, dose-finding study. Osteoporos Int. 2014 Jan;25(1):367-76. doi: 10.1007/s00198-013-2398-2. Epub 2013 May 29.

  PMID: 23716037 BACKGROUND

MeSH Terms

Conditions

Osteoporosis, Postmenopausal

Interventions

odanacatib; Cholecalciferol; Calcium Carbonate

Condition Hierarchy (Ancestors)

Osteoporosis; 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

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 Director

  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 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 21, 2008
• Study Start: December 3, 2007
• Primary Completion: May 29, 2009
• Study Completion: May 29, 2009
• Last Updated: August 27, 2018
• Results First Posted: March 13, 2017

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share