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| ID | Type | Description | Link |
|---|---|---|---|
| MK-0822-022 | Other Identifier | Merck Registration Number | |
| 2007_034 | Other Identifier | Merck |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| Odanacatib 50 mg | Placebo Comparator |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Odanacatib | Drug | Odanacatib tablets 10 mg, 25 mg, or 50 mg (depending upon randomization), taken orally once weekly for 52 weeks. |
|
| 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. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23716037 | Background | 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. |
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Of 403 participants screened, 287 participants were randomized to treatment on study. 286 participants received the correct treatment on study and were used for safety and efficacy analyses. One participant in the odanacatib 25 mg group also received 50 mg odanacatib during study by mistake and was excluded from all analyses.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | 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. |
| FG001 | Odanacatib 10 mg | 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. |
| FG002 | Odanacatib 25 mg | 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. |
| FG003 | Odanacatib 50 mg | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Population: All randomized participants receiving at least one dose of correct study medication. One participant received both 25 mg and 50 mg doses during the study and was excluded from all analyses.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | 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 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Full Analysis Set (FAS): All randomized participants receiving at least one dose of study medication and with necessary on-treatment lumbar spine BMD measurements, with data carried forward. | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline (Observation visit to Wk 0 treatment visit), Week 52 |
|
From first dose up to Post-Study (up to 54 weeks)
Safety Population: All randomized participants receiving at least one dose of correct study medication. One participant received both 25 mg and 50 mg doses and was excluded from all analyses.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | 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 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina pectoris | Cardiac disorders | MedDRA 12.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D015663 | Osteoporosis, Postmenopausal |
| ID | Term |
|---|---|
| D010024 | Osteoporosis |
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| C527128 | odanacatib |
| D002762 | Cholecalciferol |
| D002119 | Calcium Carbonate |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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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. |
|
|
| Vitamin D3 | Dietary Supplement | Two Vitamin D3 tablets (5600 IU total) taken orally once weekly for 52 weeks. |
|
|
| Calcium carbonate | Dietary Supplement | Calcium carbonate 500 mg tablet taken orally every day for 52 weeks. |
|
| Placebo | Drug | Dose-matched placebo tablets to odanacatib, taken orally once weekly for 52 weeks. |
|
| From first dose up to end of treatment (up to 52 weeks) |
| 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 |
| Lack of Efficacy |
|
| Physician Decision |
|
| Protocol Violation |
|
| Withdrawal by Subject |
|
| BG001 | Odanacatib 10 mg | 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. |
| BG002 | Odanacatib 25 mg | 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. |
| BG003 | Odanacatib 50 mg | 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. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Title |
|---|
| Description |
|---|
| OG000 | Placebo | 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 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. |
| OG001 | Odanacatib 10 mg | 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. |
| OG002 | Odanacatib 25 mg | 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. |
| OG003 | Odanacatib 50 mg | 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. |
|
|
|
| Secondary | 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. | FAS: All randomized participants receiving at least one dose of study medication and with necessary on-treatment total hip BMD measurements, with data carried forward. | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline (Observation visit to Wk 0 treatment visit), Week 52 |
|
|
|
|
| Primary | 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. | Safety Population: All randomized participants receiving at least one dose of correct study medication. One participant received both 25 mg and 50 mg doses and was excluded from all analyses. | Posted | Number | participants | From first dose up to Post-Study (up to 54 weeks) |
|
|
|
| Primary | 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. | Safety Population: All randomized participants receiving at least one dose of correct study medication. One participant received both 25 mg and 50 mg doses and was excluded from all analyses. | Posted | Number | participants | From first dose up to end of treatment (up to 52 weeks) |
|
|
|
| Secondary | 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. | FAS: All randomized participants receiving at least one dose of study medication and with necessary on-treatment femoral neck BMD measurements, with data carried forward. | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline (Observation visit to Wk 0 treatment visit), Week 52 |
|
|
|
|
| Secondary | 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. | FAS: All randomized participants receiving at least one dose of study medication and with necessary on-treatment trochanter BMD measurements, with data carried forward. | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline (Observation visit to Wk 0 treatment visit), Week 52 |
|
|
|
|
| Secondary | 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. | Per Protocol (PP) Population: All randomized participants receiving at least one dose of study medication, who complied with the protocol (excludes participants with major protocol violation), and with available u-NTx/Cre data. | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline (Wk 0), Week 52 |
|
|
|
|
| Secondary | 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. | PP Population: All randomized participants receiving at least one dose of study medication, who complied with the protocol (excludes participants with major protocol violation), and with available s-CTx data. | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline (Wk 0), Week 52 |
|
|
|
|
| Secondary | 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. | PP Population: All randomized participants receiving at least one dose of study medication, who complied with the protocol (excludes participants with major protocol violation), and with available u-DPD/Cre data. | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline (Wk 0), Week 52 |
|
|
|
|
| Secondary | 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. | PP Population: All randomized participants receiving at least one dose of study medication, who complied with the protocol (excludes participants with major protocol violation), and with available s-BSAP data. | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline (Wk 0), Week 52 |
|
|
|
|
| Secondary | 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. | PP Population: All randomized participants receiving at least one dose of study medication, who complied with the protocol (excludes participants with major protocol violation), and with available s-P1NP data. | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline (Wk 0), Week 52 |
|
|
|
|
| 5 |
| 73 |
| 46 |
| 73 |
| EG001 | Odanacatib 10 mg | 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. | 6 | 74 | 46 | 74 |
| EG002 | Odanacatib 25 mg | 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. | 4 | 70 | 50 | 70 |
| EG003 | Odanacatib 50 mg | 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. | 4 | 69 | 51 | 69 |
| Myocardial ischaemia | Cardiac disorders | MedDRA 12.0 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 12.0 | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA 12.0 | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
|
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 12.0 | Systematic Assessment |
|
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 12.0 | Systematic Assessment |
|
| Foot deformity | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
|
| Adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 12.0 | Systematic Assessment |
|
| Lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 12.0 | Systematic Assessment |
|
| Cerebellar haemorrhage | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
|
| Intraneural cyst | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
|
| Subarachnoid haemorrhage | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
|
| Transient ischaemic attack | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
|
| Neurosis | Psychiatric disorders | MedDRA 12.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Periodontitis | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 12.0 | Systematic Assessment |
|
| Joint sprain | Injury, poisoning and procedural complications | MedDRA 12.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 12.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
|
| Periarthritis | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
|
| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
|
The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication guidelines.
| D008659 |
| Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D011083 |
| Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |
| D017610 | Calcium Compounds |
| D007287 | Inorganic Chemicals |
| D002254 | Carbonates |
| D002255 | Carbonic Acid |
| D017554 | Carbon Compounds, Inorganic |
| D008903 | Minerals |
| Superiority or Other |
| Analysis for percent change from baseline to Week 52 in BMD was performed using a stepwise linear contrast test based on an ANCOVA model with terms for treatment and study center. Treatment effect was assessed by LS mean and the associated 95% confidence intervals. Estimated difference from placebo = odanacatib dose minus placebo dose. Positive mean treatment differences were in favor of odanacatib. | ANCOVA | <0.001 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 25 mg dose. | Difference in LS Means | 2.20 | 2-Sided | 95 | 1.29 | 3.12 | Superiority or Other |
| Analysis for percent change from baseline to Week 52 in BMD was performed using a stepwise linear contrast test based on an ANCOVA model with terms for treatment and study center. Treatment effect was assessed by LS mean and the associated 95% confidence intervals. Estimated difference from placebo = odanacatib dose minus placebo dose. Positive mean treatment differences were in favor of odanacatib. | ANCOVA | <0.001 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 10 mg dose. | Difference in LS Means | 1.67 | 2-Sided | 95 | 0.77 | 2.57 | Superiority or Other |
| Superiority or Other |
| Analysis for percent change from baseline to Week 52 in BMD was performed using a stepwise linear contrast test based on an ANCOVA model with terms for treatment and study center. Treatment effect was assessed by LS mean and the associated 95% confidence intervals. Estimated difference from placebo = odanacatib dose minus placebo dose. Positive mean treatment differences were in favor of odanacatib. | ANCOVA | 0.003 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 25 mg dose. | Difference in LS Means | 1.86 | 2-Sided | 95 | 0.64 | 3.08 | Superiority or Other |
| Analysis for percent change from baseline to Week 52 in BMD was performed using a stepwise linear contrast test based on an ANCOVA model with terms for treatment and study center. Treatment effect was assessed by LS mean and the associated 95% confidence intervals. Estimated difference from placebo = odanacatib dose minus placebo dose. Positive mean treatment differences were in favor of odanacatib. | ANCOVA | <0.001 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 10 mg dose. | Difference in LS Means | 2.23 | 2-Sided | 95 | 1.03 | 3.43 | Superiority or Other |
| Superiority or Other |
| Analysis for percent change from baseline to Week 52 in BMD was performed using a stepwise linear contrast test based on an ANCOVA model with terms for treatment and study center. Treatment effect was assessed by LS mean and the associated 95% confidence intervals. Estimated difference from placebo = odanacatib dose minus placebo dose. Positive mean treatment differences were in favor of odanacatib. | ANCOVA | <0.001 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 25 mg dose. | Difference in LS Means | 3.84 | 2-Sided | 95 | 2.37 | 5.30 | Superiority or Other |
| Analysis for percent change from baseline to Week 52 in BMD was performed using a stepwise linear contrast test based on an ANCOVA model with terms for treatment and study center. Treatment effect was assessed by LS mean and the associated 95% confidence intervals. Estimated difference from placebo = odanacatib dose minus placebo dose. Positive mean treatment differences were in favor of odanacatib. | ANCOVA | 0.002 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 10 mg dose. | Difference in LS Means | 2.43 | 2-Sided | 95 | 0.99 | 3.88 | Superiority or Other |
| Superiority or Other |
| The log-transformed fraction from baseline in biomarker levels was analyzed using an ANCOVA model with terms for treatment and study center, using a stepwise linear contrast test based on the ANCOVA model. The geometric mean percent change from baseline (back-transformation from the mean log-transformed fraction) and the associated 95% confidence intervals were presented. | ANCOVA | <0.001 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 25 mg dose. | Difference in LS Means | -44.32 | 2-Sided | 95 | -60.42 | -28.21 | Superiority or Other |
| The log-transformed fraction from baseline in biomarker levels was analyzed using an ANCOVA model with terms for treatment and study center, using a stepwise linear contrast test based on the ANCOVA model. The geometric mean percent change from baseline (back-transformation from the mean log-transformed fraction) and the associated 95% confidence intervals were presented. | ANCOVA | <0.001 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 10 mg dose. | Difference in LS Means | -35.75 | 2-Sided | 95 | -52.33 | -19.16 | Superiority or Other |
| Superiority or Other |
| The log-transformed fraction from baseline in biomarker levels was analyzed using an ANCOVA model with terms for treatment and study center, using a stepwise linear contrast test based on the ANCOVA model. The geometric mean percent change from baseline (back-transformation from the mean log-transformed fraction) and the associated 95% confidence intervals were presented. | ANCOVA | <0.001 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 25 mg dose. | Difference in LS Means | -60.70 | 2-Sided | 95 | -85.91 | -35.49 | Superiority or Other |
| The log-transformed fraction from baseline in biomarker levels was analyzed using an ANCOVA model with terms for treatment and study center, using a stepwise linear contrast test based on the ANCOVA model. The geometric mean percent change from baseline (back-transformation from the mean log-transformed fraction) and the associated 95% confidence intervals were presented. | ANCOVA | <0.001 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 10 mg dose. | Difference in LS Means | -38.73 | 2-Sided | 95 | -65.94 | -11.52 | Superiority or Other |
| Superiority or Other |
| The log-transformed fraction from baseline in biomarker levels was analyzed using an ANCOVA model with terms for treatment and study center, using a stepwise linear contrast test based on the ANCOVA model. The geometric mean percent change from baseline (back-transformation from the mean log-transformed fraction) and the associated 95% confidence intervals were presented. | ANCOVA | 0.001 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 25 mg dose. | Difference in LS Means | -37.45 | 2-Sided | 95 | -60.32 | -14.59 | Superiority or Other |
| The log-transformed fraction from baseline in biomarker levels was analyzed using an ANCOVA model with terms for treatment and study center, using a stepwise linear contrast test based on the ANCOVA model. The geometric mean percent change from baseline (back-transformation from the mean log-transformed fraction) and the associated 95% confidence intervals were presented. | ANCOVA | 0.017 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 10 mg dose. | Difference in LS Means | -26.77 | 2-Sided | 95 | -50.37 | -3.16 | Superiority or Other |
| Superiority or Other |
| The log-transformed fraction from baseline in biomarker levels was analyzed using an ANCOVA model with terms for treatment and study center, using a stepwise linear contrast test based on the ANCOVA model. The geometric mean percent change from baseline (back-transformation from the mean log-transformed fraction) and the associated 95% confidence intervals were presented. | ANCOVA | 0.009 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 25 mg dose. | Difference in LS Means | -12.55 | 2-Sided | 95 | -22.16 | -2.94 | Superiority or Other |
| The log-transformed fraction from baseline in biomarker levels was analyzed using an ANCOVA model with terms for treatment and study center, using a stepwise linear contrast test based on the ANCOVA model. The geometric mean percent change from baseline (back-transformation from the mean log-transformed fraction) and the associated 95% confidence intervals were presented. | ANCOVA | 0.598 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 10 mg dose. | Difference in LS Means | 2.48 | 2-Sided | 95 | -7.79 | 12.74 | Superiority or Other |
| Superiority or Other |
| The log-transformed fraction from baseline in biomarker levels was analyzed using an ANCOVA model with terms for treatment and study center, using a stepwise linear contrast test based on the ANCOVA model. The geometric mean percent change from baseline (back-transformation from the mean log-transformed fraction) and the associated 95% confidence intervals were presented. | ANCOVA | <0.001 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 25 mg dose. | Difference in LS Means | -28.86 | 2-Sided | 95 | -44.97 | -12.75 | Superiority or Other |
| The log-transformed fraction from baseline in biomarker levels was analyzed using an ANCOVA model with terms for treatment and study center, using a stepwise linear contrast test based on the ANCOVA model. The geometric mean percent change from baseline (back-transformation from the mean log-transformed fraction) and the associated 95% confidence intervals were presented. | ANCOVA | 0.458 | The stepwise linear trend test adjusted for multiplicity within the family of comparisons of active doses with placebo and preserved the Type I error rate. P-value is for Placebo through Odanacatib 10 mg dose. | Difference in LS Means | -5.61 | 2-Sided | 95 | -23.79 | 12.56 | Superiority or Other |