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

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Dose-Finding Study of MK-0822 in the Treatment of Involutional Osteoporosis

Conditions
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Osteoporosis Postmenopausal

Intervention / Treatment
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* Drug: Odanacatib
* Dietary Supplement: Vitamin D3
* Dietary Supplement: Calcium carbonate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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<br>* Two Vitamin D3 tablets (5600 IU total) taken orally once weekly for 52 weeks.<br>* Other names: cholecalciferol;Dietary Supplement: Calcium carbonate<br>* Calcium carbonate 500 mg tablet taken orally every day for 52 weeks.<br>Drug: Placebo<br>* Dose-matched placebo tablets to odanacatib, taken orally once weekly for 52 weeks.<br>|
| Experimental: Odanacatib 10 mg<br>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<br>* Odanacatib tablets 10 mg, 25 mg, or 50 mg (depending upon randomization), taken orally once weekly for 52 weeks.<br>* Other names: MK-0822;Dietary Supplement: Vitamin D3<br>* Two Vitamin D3 tablets (5600 IU total) taken orally once weekly for 52 weeks.<br>* Other names: cholecalciferol;Dietary Supplement: Calcium carbonate<br>* Calcium carbonate 500 mg tablet taken orally every day for 52 weeks.<br>|
| Experimental: Odanacatib 25 mg<br>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<br>* Odanacatib tablets 10 mg, 25 mg, or 50 mg (depending upon randomization), taken orally once weekly for 52 weeks.<br>* Other names: MK-0822;Dietary Supplement: Vitamin D3<br>* Two Vitamin D3 tablets (5600 IU total) taken orally once weekly for 52 weeks.<br>* Other names: cholecalciferol;Dietary Supplement: Calcium carbonate<br>* Calcium carbonate 500 mg tablet taken orally every day for 52 weeks.<br>|
| Placebo Comparator: Odanacatib 50 mg<br>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<br>* Odanacatib tablets 10 mg, 25 mg, or 50 mg (depending upon randomization), taken orally once weekly for 52 weeks.<br>* Other names: MK-0822;Dietary Supplement: Vitamin D3<br>* Two Vitamin D3 tablets (5600 IU total) taken orally once weekly for 52 weeks.<br>* Other names: cholecalciferol;Dietary Supplement: Calcium carbonate<br>* Calcium carbonate 500 mg tablet taken orally every day for 52 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 52 in Total Hip BMD | BMD (g/cm2) data was measured by DXA for total hip 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 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 | 
| Percent Change From Baseline to Week 52 in Femoral Neck BMD | BMD (g/cm2) data was measured by DXA at the femoral neck subregion of the hip 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 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 | 
| Percent Change From Baseline to Week 52 in Trochanter BMD | BMD (g/cm2) data was measured by DXA at the trochanter subregion of the hip (near bony protrusions along outside edge of femur) 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 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 | 
| Percent Change From Baseline to Week 52 in Urinary N-telopeptides/Creatinine (u-NTx/Cre) Ratio | The u-NTx/Cre ratio is a biochemical marker index of bone resorption. Urine samples were collected from second void morning urine specimens to assess the u-NTx/Cre ratio. Percent change from baseline in biomarker = ([biomarker value at Week 52 visit] - [baseline biomarker value] ÷ baseline biomarker value) × 100. All measurements of bone biochemical markers were centrally performed. | Baseline (Wk 0), Week 52 | 
| Percent Change From Baseline to Week 52 in Serum C-Telopeptides of Type 1 Collagen (s-CTx) Level | s-CTx is a biochemical marker index of bone resorption. Blood samples were collected in the morning and in fasting state for measurement of s-CTx. Percent change from baseline in biomarker = ([biomarker value at Week 52 visit] - [baseline biomarker value] ÷ baseline biomarker value) × 100. All measurements of bone biochemical markers were centrally performed. | Baseline (Wk 0), Week 52 | 
| Percent Change From Baseline to Week 52 in Urinary Deoxypyridinoline/Creatinine Ratio (u-DPD/Cre) | The u-DPD/Cre ratio is a biochemical marker index of bone resorption. Urine samples were collected from second void morning urine specimens to assess the u-DPD/Cre ratio. Percent change from baseline in biomarker = ([biomarker value at Week 52 visit] - [baseline biomarker value] ÷ baseline biomarker value) × 100. All measurements of bone biochemical markers were centrally performed. | Baseline (Wk 0), Week 52 | 
| Percent Change From Baseline to Week 52 in Serum Bone Specific Alkaline Phosphatase (s-BSAP) Level | s-BSAP is a biochemical marker index of bone formation. Blood samples were collected in the morning and in fasting state for measurement of s-BSAP. Percent change from baseline in biomarker = ([biomarker value at Week 52 visit] - [baseline biomarker value] ÷ baseline biomarker value) × 100. All measurements of bone biochemical markers were centrally performed. | Baseline (Wk 0), Week 52 | 
| Percent Change From Baseline to Week 52 in Serum N-Terminal Propeptides of Type 1 Collagen (s-P1NP) Level | s-P1NP is a biochemical marker index of bone formation. Blood samples were collected in the morning and in fasting state for measurement of s- P1NP. Percent change from baseline in biomarker = ([biomarker value at Week 52 visit] - [baseline biomarker value] ÷ baseline biomarker value) × 100. All measurements of bone biochemical markers were centrally performed. | Baseline (Wk 0), Week 52 |