Osteoporosis Postmenopausal
Conditions
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.
Interventions
DRUGOdanacatib
Odanacatib tablets 10 mg, 25 mg, or 50 mg (depending upon randomization), taken orally once weekly for 52 weeks.
DIETARY_SUPPLEMENTVitamin D3
Two Vitamin D3 tablets (5600 IU total) taken orally once weekly for 52 weeks.
DIETARY_SUPPLEMENTCalcium carbonate
Calcium carbonate 500 mg tablet taken orally every day for 52 weeks.
DRUGPlacebo
Dose-matched placebo tablets to odanacatib, taken orally once weekly for 52 weeks.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 52 in Lumbar Spine Bone Mineral Density (BMD) at Lumbar Vertebrae 1 to 4 (L1-L4) | Baseline (Observation visit to Wk 0 treatment visit), Week 52 | 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. |
| Number of Participants That Experienced an Adverse Event (AE) | From first dose up to Post-Study (up to 54 weeks) | 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. |
| Number of Participants That Discontinued Study Drug Due to an AE | From first dose up to end of treatment (up to 52 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 52 in Urinary N-telopeptides/Creatinine (u-NTx/Cre) Ratio | Baseline (Wk 0), Week 52 | 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. |
| Percent Change From Baseline to Week 52 in Serum C-Telopeptides of Type 1 Collagen (s-CTx) Level | Baseline (Wk 0), Week 52 | 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. |
| Percent Change From Baseline to Week 52 in Total Hip BMD | Baseline (Observation visit to Wk 0 treatment visit), Week 52 | 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. |
| Percent Change From Baseline to Week 52 in Serum Bone Specific Alkaline Phosphatase (s-BSAP) Level | Baseline (Wk 0), Week 52 | 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. |
| Percent Change From Baseline to Week 52 in Serum N-Terminal Propeptides of Type 1 Collagen (s-P1NP) Level | Baseline (Wk 0), Week 52 | 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. |
| Percent Change From Baseline to Week 52 in Urinary Deoxypyridinoline/Creatinine Ratio (u-DPD/Cre) | Baseline (Wk 0), Week 52 | 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. |
| Percent Change From Baseline to Week 52 in Femoral Neck BMD | Baseline (Observation visit to Wk 0 treatment visit), Week 52 | 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. |
| Percent Change From Baseline to Week 52 in Trochanter BMD | Baseline (Observation visit to Wk 0 treatment visit), Week 52 | 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. |
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 73 |
| 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. | 74 |
| 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. | 70 |
| 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. | 69 |
| Total | 286 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 2 | 1 |
| Overall Study | Lack of Efficacy | 2 | 3 | 0 | 2 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 2 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 1 | 3 | 5 |
Baseline characteristics
| Characteristic | Placebo | Odanacatib 10 mg | Odanacatib 25 mg | Odanacatib 50 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 67.7 years STANDARD_DEVIATION 6.8 | 69.1 years STANDARD_DEVIATION 7.3 | 67.5 years STANDARD_DEVIATION 7.4 | 68.7 years STANDARD_DEVIATION 7 | 68.2 years STANDARD_DEVIATION 7.1 |
| Sex: Female, Male Female | 70 Participants | 69 Participants | 63 Participants | 67 Participants | 269 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 7 Participants | 2 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 46 / 73 | 46 / 74 | 50 / 70 | 51 / 69 |
| serious Total, serious adverse events | 5 / 73 | 6 / 74 | 4 / 70 | 4 / 69 |
Outcome results
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.
Time frame: From first dose up to end of treatment (up to 52 weeks)
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants That Discontinued Study Drug Due to an AE | 3 participants |
| Odanacatib 10 mg | Number of Participants That Discontinued Study Drug Due to an AE | 2 participants |
| Odanacatib 25 mg | Number of Participants That Discontinued Study Drug Due to an AE | 1 participants |
| Odanacatib 50 mg | Number of Participants That Discontinued Study Drug Due to an AE | 1 participants |
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.
Time frame: From first dose up to Post-Study (up to 54 weeks)
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants That Experienced an Adverse Event (AE) | 57 participants |
| Odanacatib 10 mg | Number of Participants That Experienced an Adverse Event (AE) | 63 participants |
| Odanacatib 25 mg | Number of Participants That Experienced an Adverse Event (AE) | 62 participants |
| Odanacatib 50 mg | Number of Participants That Experienced an Adverse Event (AE) | 58 participants |
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.
Time frame: Baseline (Observation visit to Wk 0 treatment visit), Week 52
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in Lumbar Spine Bone Mineral Density (BMD) at Lumbar Vertebrae 1 to 4 (L1-L4) | 0.55 percent change |
| Odanacatib 10 mg | Percent Change From Baseline to Week 52 in Lumbar Spine Bone Mineral Density (BMD) at Lumbar Vertebrae 1 to 4 (L1-L4) | 4.09 percent change |
| Odanacatib 25 mg | Percent Change From Baseline to Week 52 in Lumbar Spine Bone Mineral Density (BMD) at Lumbar Vertebrae 1 to 4 (L1-L4) | 5.67 percent change |
| Odanacatib 50 mg | Percent Change From Baseline to Week 52 in Lumbar Spine Bone Mineral Density (BMD) at Lumbar Vertebrae 1 to 4 (L1-L4) | 5.94 percent change |
Comparison: Analysis for percent change from baseline to Week 52 in BMD was performed using a stepwise linear contrast test based on an analysis of covariance (ANCOVA) model with terms for treatment and study center. Treatment effect was assessed by Least-Squares means (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.p-value: <0.00195% CI: [4.16, 6.64]ANCOVA
Comparison: 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.p-value: <0.00195% CI: [3.9, 6.35]ANCOVA
Comparison: 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.p-value: <0.00195% CI: [2.33, 4.75]ANCOVA
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.
Time frame: Baseline (Observation visit to Wk 0 treatment visit), Week 52
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in Femoral Neck BMD | -0.72 percent change |
| Odanacatib 10 mg | Percent Change From Baseline to Week 52 in Femoral Neck BMD | 1.51 percent change |
| Odanacatib 25 mg | Percent Change From Baseline to Week 52 in Femoral Neck BMD | 1.14 percent change |
| Odanacatib 50 mg | Percent Change From Baseline to Week 52 in Femoral Neck BMD | 2.35 percent change |
Comparison: 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.p-value: <0.00195% CI: [1.85, 4.31]ANCOVA
Comparison: 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.p-value: 0.00395% CI: [0.64, 3.08]ANCOVA
Comparison: 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.p-value: <0.00195% CI: [1.03, 3.43]ANCOVA
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.
Time frame: Baseline (Wk 0), Week 52
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in Serum Bone Specific Alkaline Phosphatase (s-BSAP) Level | -9.91 percent change |
| Odanacatib 10 mg | Percent Change From Baseline to Week 52 in Serum Bone Specific Alkaline Phosphatase (s-BSAP) Level | -7.44 percent change |
| Odanacatib 25 mg | Percent Change From Baseline to Week 52 in Serum Bone Specific Alkaline Phosphatase (s-BSAP) Level | -22.47 percent change |
| Odanacatib 50 mg | Percent Change From Baseline to Week 52 in Serum Bone Specific Alkaline Phosphatase (s-BSAP) Level | -25.43 percent change |
Comparison: 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.p-value: <0.00195% CI: [-25.11, -5.93]ANCOVA
Comparison: 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.p-value: 0.00995% CI: [-22.16, -2.94]ANCOVA
Comparison: 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.p-value: 0.59895% CI: [-7.79, 12.74]ANCOVA
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.
Time frame: Baseline (Wk 0), Week 52
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in Serum C-Telopeptides of Type 1 Collagen (s-CTx) Level | -10.95 percent change |
| Odanacatib 10 mg | Percent Change From Baseline to Week 52 in Serum C-Telopeptides of Type 1 Collagen (s-CTx) Level | -49.68 percent change |
| Odanacatib 25 mg | Percent Change From Baseline to Week 52 in Serum C-Telopeptides of Type 1 Collagen (s-CTx) Level | -71.64 percent change |
| Odanacatib 50 mg | Percent Change From Baseline to Week 52 in Serum C-Telopeptides of Type 1 Collagen (s-CTx) Level | -71.36 percent change |
Comparison: 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.p-value: <0.00195% CI: [-85.7, -35.13]ANCOVA
Comparison: 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.p-value: <0.00195% CI: [-85.91, -35.49]ANCOVA
Comparison: 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.p-value: <0.00195% CI: [-65.94, -11.52]ANCOVA
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.
Time frame: Baseline (Wk 0), Week 52
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in Serum N-Terminal Propeptides of Type 1 Collagen (s-P1NP) Level | -20.14 percent change |
| Odanacatib 10 mg | Percent Change From Baseline to Week 52 in Serum N-Terminal Propeptides of Type 1 Collagen (s-P1NP) Level | -25.75 percent change |
| Odanacatib 25 mg | Percent Change From Baseline to Week 52 in Serum N-Terminal Propeptides of Type 1 Collagen (s-P1NP) Level | -48.99 percent change |
| Odanacatib 50 mg | Percent Change From Baseline to Week 52 in Serum N-Terminal Propeptides of Type 1 Collagen (s-P1NP) Level | -47.00 percent change |
Comparison: 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.p-value: <0.00195% CI: [-43.3, -10.42]ANCOVA
Comparison: 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.p-value: <0.00195% CI: [-44.97, -12.75]ANCOVA
Comparison: 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.p-value: 0.45895% CI: [-23.79, 12.56]ANCOVA
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.
Time frame: Baseline (Observation visit to Wk 0 treatment visit), Week 52
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in Total Hip BMD | -0.35 percent change |
| Odanacatib 10 mg | Percent Change From Baseline to Week 52 in Total Hip BMD | 1.31 percent change |
| Odanacatib 25 mg | Percent Change From Baseline to Week 52 in Total Hip BMD | 1.85 percent change |
| Odanacatib 50 mg | Percent Change From Baseline to Week 52 in Total Hip BMD | 2.70 percent change |
Comparison: 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.p-value: <0.00195% CI: [2.14, 3.98]ANCOVA
Comparison: 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.p-value: <0.00195% CI: [1.29, 3.12]ANCOVA
Comparison: 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.p-value: <0.00195% CI: [0.77, 2.57]ANCOVA
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.
Time frame: Baseline (Observation visit to Wk 0 treatment visit), Week 52
Population: FAS: All randomized participants receiving at least one dose of study medication and with necessary on-treatment trochanter BMD measurements, with data carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in Trochanter BMD | -0.28 percent change |
| Odanacatib 10 mg | Percent Change From Baseline to Week 52 in Trochanter BMD | 2.16 percent change |
| Odanacatib 25 mg | Percent Change From Baseline to Week 52 in Trochanter BMD | 3.56 percent change |
| Odanacatib 50 mg | Percent Change From Baseline to Week 52 in Trochanter BMD | 4.38 percent change |
Comparison: 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.p-value: <0.00195% CI: [3.18, 6.14]ANCOVA
Comparison: 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.p-value: <0.00195% CI: [2.37, 5.3]ANCOVA
Comparison: 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.p-value: 0.00295% CI: [0.99, 3.88]ANCOVA
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.
Time frame: Baseline (Wk 0), Week 52
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in Urinary Deoxypyridinoline/Creatinine Ratio (u-DPD/Cre) | 16.45 percent change |
| Odanacatib 10 mg | Percent Change From Baseline to Week 52 in Urinary Deoxypyridinoline/Creatinine Ratio (u-DPD/Cre) | -10.32 percent change |
| Odanacatib 25 mg | Percent Change From Baseline to Week 52 in Urinary Deoxypyridinoline/Creatinine Ratio (u-DPD/Cre) | -21.00 percent change |
| Odanacatib 50 mg | Percent Change From Baseline to Week 52 in Urinary Deoxypyridinoline/Creatinine Ratio (u-DPD/Cre) | -26.46 percent change |
Comparison: 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.p-value: <0.00195% CI: [-65.55, -20.27]ANCOVA
Comparison: 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.p-value: 0.00195% CI: [-60.32, -14.59]ANCOVA
Comparison: 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.p-value: 0.01795% CI: [-50.37, -3.16]ANCOVA
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.
Time frame: Baseline (Wk 0), Week 52
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in Urinary N-telopeptides/Creatinine (u-NTx/Cre) Ratio | -7.84 percent change |
| Odanacatib 10 mg | Percent Change From Baseline to Week 52 in Urinary N-telopeptides/Creatinine (u-NTx/Cre) Ratio | -43.59 percent change |
| Odanacatib 25 mg | Percent Change From Baseline to Week 52 in Urinary N-telopeptides/Creatinine (u-NTx/Cre) Ratio | -52.16 percent change |
| Odanacatib 50 mg | Percent Change From Baseline to Week 52 in Urinary N-telopeptides/Creatinine (u-NTx/Cre) Ratio | -58.48 percent change |
Comparison: 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.p-value: <0.00195% CI: [-66.43, -34.84]ANCOVA
Comparison: 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.p-value: <0.00195% CI: [-60.42, -28.21]ANCOVA
Comparison: 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.p-value: <0.00195% CI: [-52.33, -19.16]ANCOVA