Osteoporosis
Conditions
Brief summary
The study will evaluate the both the efficacy of odanacatib on Bone Mineral Density (BMD) and the safety of odanacatib for postmenopausal osteoporosis in patients previously treated with alendronate. The primary hypothesis of the trial is that treatment with odanacatib 50 mg once weekly will increase bone mineral density at the femoral neck compared to placebo at the end of 24 months.
Interventions
DRUGOdanacatib
Odanacatib 50 mg tablets once weekly for 24 months
DRUGPlacebo
Placebo to odanacatib 50 mg tablets once weekly for 24 months
DIETARY_SUPPLEMENTVitamin D3
Vitamin D3, two 2800 IU tablets, taken once weekly for 24 months
DIETARY_SUPPLEMENTCalcium
Participants will receive calcium carbonate supplements as needed to ensure a daily calcium intake of 1200 mg.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has been postmenopausal for at least 5 years * Has taken or is taking alendronate * Agrees not to use medications for osteoporosis other than what is provided by the study
Exclusion criteria
* Has a history or evidence of hip fracture * Has a history of cancer within 5 years of screening, except certain skin or cervical cancers. * Has active parathyroid disease * Has a history of thyroid disease not adequately controlled by medication * Is taking anti-seizure medication and has abnormal calcium metabolism * Has received any bisphosphonate other than alendronate for 20% of the last 3 years, or within 3 months of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at Month 24 | Baseline and Month 24 | BMD at the femoral neck was assessed by dual-energy X-ray absorptiometry (DXA) at baseline and Month 24. |
| Percentage of Participants Experiencing One or More Adverse Events (AEs) | Up to 25 months | An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. |
| Percentage of Participants Discontinuing Study Drug Due to an AE | Up to 24 months | An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Total Hip BMD at Month 24 | Baseline and 24 Months | BMD at the total hip was assessed by DXA at baseline and Month 24. |
| Percent Change From Baseline in Total Hip BMD at Month 12 | Baseline and 12 Months | BMD at the total hip was assessed by DXA at baseline and Month 12. |
| Percent Change From Baseline in Lumbar Spine BMD at Month 24 | Baseline and 24 Months | BMD at the lumbar spine was assessed by DXA at baseline and Month 24. |
| Percent Change From Baseline in Lumbar Spine BMD at Month 12 | Baseline and 12 Months | BMD at the lumbar spine was assessed by DXA at baseline and Month 12. |
| Percent Change From Baseline in 1/3 Distal Forearm BMD at Month 24 | Baseline and 24 Months | BMD at the 1/3 distal forearm was assessed by DXA at baseline and Month 24. |
| Percent Change From Baseline in 1/3 Distal Forearm BMD at Month 12 | Baseline and 12 Months | BMD at the 1/3 distal forearm was assessed by DXA at baseline and Month 12. |
| Percent Change From Baseline in Log-Transformed Serum C-Telopeptides of Type I Collagen (s-CTx) at Month 24 | Baseline and Month 24 | s-CTx is a biochemical marker of bone resorption. |
| Percent Change From Baseline in Log-Transformed s-CTx at Month 12 | Baseline and Month 12 | s-CTx is a biochemical marker of bone resorption. |
| Percent Change From Baseline in Log-Transformed Urine N-Telopeptides/Creatinine Ratio at Month 24 | Baseline and Month 24 | N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio (u-NTx/Cr) is a biochemical marker of bone resorption. |
| Percent Change From Baseline in Femoral Neck BMD at Month 12 | Baseline and 12 Months | BMD at the femoral neck was assessed by DXA at baseline and Month 12. |
| Percent Change From Baseline in Log-Transformed Serum Bone-Specific Alkaline Phosphatase at Month 24 | Baseline and Month 24 | Bone-Specific Alkaline Phosphatase (BSAP) is a biochemical marker of bone formation. |
| Percent Change From Baseline in Log-Transformed Serum BSAP at Month 12 | Baseline and Month 12 | BSAP is a biochemical marker of bone formation. |
| Percent Change From Baseline in Log-Transformed Serum N-Terminal Propeptide of Type I Collagen at Month 24 | Baseline and Month 24 | Serum N-terminal propeptide of Type I collagen (s-P1NP) is a biochemical marker of bone formation. |
| Percent Change From Baseline in Log-Transformed Serum N-terminal Propeptide of Type I Collagen at Month 12 | Baseline and Month 12 | s-P1NP is a biochemical marker of bone formation. |
| Percent Change From Baseline in Log-Transformed Serum Calcium at Month 24 | Baseline and Month 24 | Serum calcium is an index of calcium homeostasis. |
| Percent Change From Baseline in Log-Transformed Serum Phosphate at Month 24 | Baseline and Month 24 | Serum phosphate is an index of mineral homeostasis. |
| Percent Change From Baseline in Log-Transformed Serum Parathyroid Hormone at Month 24 | Baseline and Month 24 | Serum parathyroid hormone (SPH) regulates calcium, phosphorus, and vitamin D levels in the blood. |
| Percent Change From Baseline in Log-Transformed Serum 1,25 Dihydroxyvitamin D at Month 24 | Baseline and Month 24 | 1,25 dihydroxyvitamin D \[1,25(OH)2 D\] is the active vitamin D metabolite and stimulates calcium absorption in the intestine. |
| Percent Change From Baseline in Log-Transformed Serum 25-Hydroxyvitamin D at Month 24 | Baseline and Month 24 | The 25-hydroxy vitamin D \[25(OH)D\] test is the most accurate way to measure vitamin D. In the kidney, 25-hydroxy vitamin D is converted into 1,25 di-hydroxyvitamin D, the active vitamin D metabolite. |
| Percent Change From Baseline in Log-Transformed u-NTx/Cr at Month 12 | Baseline and Month 12 | u-NTx/Cr is a biochemical marker of bone resorption. |
| Percent Change From Baseline in Trochanter BMD at Month 24 | Baseline and 24 Months | BMD at the trochanter was assessed by DXA at baseline and Month 24. |
| Percent Change From Baseline in Trochanter BMD at Month 12 | Baseline and 12 Months | BMD at the trochanter was assessed by DXA at baseline and Month 12. |
Participant flow
Recruitment details
Participants were enrolled and treated in 40 study centers located in the United States, Europe, South Africa, and Asia-Pacific.
Pre-assignment details
Women ≥ 60 years of age who had been on, or were on, an alendronate therapy for postmenopausal osteoporosis were eligible to participate in this trial.
Participants by arm
| Arm | Count |
|---|---|
| Odanacatib 50 mg Odanacatib 50 mg tablets once weekly for 24 months. Vitamin D3 (dietary supplement), two 2800 IU tablets, taken once weekly for 24 months. Participants received calcium carbonate supplements as needed to ensure a daily calcium intake of approximately 1200 mg. | 122 |
| Placebo Placebo to odanacatib 50 mg tablets once weekly for 24 months. Vitamin D3 (dietary supplement), two 2800 IU tablets, taken once weekly for 24 months. Participants received calcium carbonate supplements as needed to ensure a daily calcium intake of approximately 1200 mg. | 121 |
| Total | 243 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 4 |
| Overall Study | Excessive bone loss | 6 | 3 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Withdrawal by Subject | 13 | 13 |
Baseline characteristics
| Characteristic | Odanacatib 50 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 71.5 Years STANDARD_DEVIATION 6.7 | 71.1 Years STANDARD_DEVIATION 6.8 | 71.3 Years STANDARD_DEVIATION 6.8 |
| Baseline Biochemical Markers of Bone Resorption and Bone Formation C-telopeptides of Type 1 collage (116, 117,233) | 0.19 ng/mL STANDARD_DEVIATION 0.22 | 0.18 ng/mL STANDARD_DEVIATION 0.14 | 0.19 ng/mL STANDARD_DEVIATION 0.19 |
| Baseline Biochemical Markers of Bone Resorption and Bone Formation Serum bone specific alk. phosphatase (115,117,232) | 9.28 ng/mL STANDARD_DEVIATION 4.63 | 9.41 ng/mL STANDARD_DEVIATION 4.16 | 9.35 ng/mL STANDARD_DEVIATION 4.39 |
| Baseline Biochemical Markers of Bone Resorption and Bone Formation Serum N-propeptide, T1 collagen (115, 117, 232) | 29.48 ng/mL STANDARD_DEVIATION 28.18 | 27.79 ng/mL STANDARD_DEVIATION 21.58 | 28.63 ng/mL STANDARD_DEVIATION 25.03 |
| Baseline DEXA Areal Bone Mineral Density T-score 1/3 Distal Forearm BMD T-score (114, 113, 227) | -2.62 T-score STANDARD_DEVIATION 1.26 | -2.69 T-score STANDARD_DEVIATION 1.1 | -2.65 T-score STANDARD_DEVIATION 1.18 |
| Baseline DEXA Areal Bone Mineral Density T-score Femoral Neck BMD T-score (122, 121, 243) | -2.35 T-score STANDARD_DEVIATION 0.52 | -2.38 T-score STANDARD_DEVIATION 0.48 | -2.36 T-score STANDARD_DEVIATION 0.5 |
| Baseline DEXA Areal Bone Mineral Density T-score Hip Trochanter BMD T-score (122, 121, 243) | -1.91 T-score STANDARD_DEVIATION 0.7 | -2.10 T-score STANDARD_DEVIATION 0.79 | -2.00 T-score STANDARD_DEVIATION 0.75 |
| Baseline DEXA Areal Bone Mineral Density T-score Lumbar Spine BMD T-score (113, 116, 229) | -2.34 T-score STANDARD_DEVIATION 1.1 | -2.49 T-score STANDARD_DEVIATION 1.14 | -2.41 T-score STANDARD_DEVIATION 1.12 |
| Baseline DEXA Areal Bone Mineral Density T-score Total Hip BMD T-score (122, 121, 243) | -1.91 T-score STANDARD_DEVIATION 0.62 | -2.05 T-score STANDARD_DEVIATION 0.68 | -1.98 T-score STANDARD_DEVIATION 0.65 |
| Sex: Female, Male Female | 122 Participants | 121 Participants | 243 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Urine N-Telopeptides/Creatinine Ratio | 26.00 nmol/mmol STANDARD_DEVIATION 23.76 | 26.35 nmol/mmol STANDARD_DEVIATION 18.08 | 26.17 nmol/mmol STANDARD_DEVIATION 21.08 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 122 | 48 / 121 |
| serious Total, serious adverse events | 20 / 122 | 20 / 121 |
Outcome results
Primary
Percentage of Participants Discontinuing Study Drug Due to an AE
An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.
Time frame: Up to 24 months
Population: The population analyzed included all participants who took at least one dose of study medication and were counted in the treatment group of the medication they actually took.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Odanacatib 50 mg | Percentage of Participants Discontinuing Study Drug Due to an AE | 9.0 Percentage of participants |
| Placebo | Percentage of Participants Discontinuing Study Drug Due to an AE | 3.3 Percentage of participants |
95% CI: [-0.4, 12.6]
Primary
Percentage of Participants Experiencing One or More Adverse Events (AEs)
An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.
Time frame: Up to 25 months
Population: The population analyzed included all participants who took at least one dose of study medication and were counted in the treatment group of the medication they actually took.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Odanacatib 50 mg | Percentage of Participants Experiencing One or More Adverse Events (AEs) | 68.0 Percentage of participants |
| Placebo | Percentage of Participants Experiencing One or More Adverse Events (AEs) | 73.6 Percentage of participants |
95% CI: [-16.9, 6]
Primary
Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at Month 24
BMD at the femoral neck was assessed by dual-energy X-ray absorptiometry (DXA) at baseline and Month 24.
Time frame: Baseline and Month 24
Population: The population analyzed included all randomized, treated participants who had femoral neck BMD data at Baseline and Month 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at Month 24 | 1.73 Percent Change |
| Placebo | Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at Month 24 | -0.94 Percent Change |
Comparison: The primary hypothesis of the study was met if; in postmenopausal women previously treated with alendronate with low BMD, two years of treatment with odanacatib 50 mg significantly increased BMD at the femoral neck site compared to placebo (p-value \< 0.001).p-value: <0.00195% CI: [1.17, 4.17]Constrained longitudinal data analysis
Secondary
Percent Change From Baseline in 1/3 Distal Forearm BMD at Month 12
BMD at the 1/3 distal forearm was assessed by DXA at baseline and Month 12.
Time frame: Baseline and 12 Months
Population: The population analyzed included all randomized, treated participants who had 1/3 distal forearm BMD data at Baseline and Month 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in 1/3 Distal Forearm BMD at Month 12 | -0.11 Percent Change |
| Placebo | Percent Change From Baseline in 1/3 Distal Forearm BMD at Month 12 | -0.49 Percent Change |
p-value: 0.57895% CI: [-0.96, 1.72]cLDA
Secondary
Percent Change From Baseline in 1/3 Distal Forearm BMD at Month 24
BMD at the 1/3 distal forearm was assessed by DXA at baseline and Month 24.
Time frame: Baseline and 24 Months
Population: The population analyzed included all randomized, treated participants who had 1/3 distal forearm BMD data at Baseline and Month 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in 1/3 Distal Forearm BMD at Month 24 | -0.92 Percent Change |
| Placebo | Percent Change From Baseline in 1/3 Distal Forearm BMD at Month 24 | -1.14 Percent Change |
p-value: 0.76395% CI: [-1.23, 1.67]cLDA
Secondary
Percent Change From Baseline in Femoral Neck BMD at Month 12
BMD at the femoral neck was assessed by DXA at baseline and Month 12.
Time frame: Baseline and 12 Months
Population: The population analyzed included all randomized, treated participants who had femoral neck BMD data at Baseline and Month 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Femoral Neck BMD at Month 12 | 0.60 Percent Change |
| Placebo | Percent Change From Baseline in Femoral Neck BMD at Month 12 | -0.28 Percent Change |
p-value: 0.16695% CI: [-0.37, 2.14]Constrained longitudinal data analysis
Secondary
Percent Change From Baseline in Log-Transformed s-CTx at Month 12
s-CTx is a biochemical marker of bone resorption.
Time frame: Baseline and Month 12
Population: The population analyzed included all randomized, treated participants who had s-CTx data at Baseline and Month 12 but excluded participants due to important protocol deviations that may have substantially affected the results such as use of concomitant medication, lack of study medication compliance, and medical history.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Log-Transformed s-CTx at Month 12 | 62.27 Percent change |
| Placebo | Percent Change From Baseline in Log-Transformed s-CTx at Month 12 | 68.09 Percent change |
p-value: 0.70995% CI: [-36.29, 24.65]cLDA
Secondary
Percent Change From Baseline in Log-Transformed Serum 1,25 Dihydroxyvitamin D at Month 24
1,25 dihydroxyvitamin D \[1,25(OH)2 D\] is the active vitamin D metabolite and stimulates calcium absorption in the intestine.
Time frame: Baseline and Month 24
Population: The population analyzed included all randomized, treated participants who had 1,25(OH)2 D data at Baseline and Month 24 but excluded participants due to important protocol deviations that may have substantially affected the results such as use of concomitant medication, lack of study medication compliance, and medical history.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Log-Transformed Serum 1,25 Dihydroxyvitamin D at Month 24 | -5.23 Percent Change |
| Placebo | Percent Change From Baseline in Log-Transformed Serum 1,25 Dihydroxyvitamin D at Month 24 | -6.71 Percent Change |
p-value: 0.83595% CI: [-12.37, 15.32]cLDA
Secondary
Percent Change From Baseline in Log-Transformed Serum 25-Hydroxyvitamin D at Month 24
The 25-hydroxy vitamin D \[25(OH)D\] test is the most accurate way to measure vitamin D. In the kidney, 25-hydroxy vitamin D is converted into 1,25 di-hydroxyvitamin D, the active vitamin D metabolite.
Time frame: Baseline and Month 24
Population: The population analyzed included all randomized, treated participants who had 25(OH)D data at Baseline and Month 24 but excluded participants due to important protocol deviations that may have substantially affected the results such as use of concomitant medication, lack of study medication compliance, and medical history.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Log-Transformed Serum 25-Hydroxyvitamin D at Month 24 | -2.57 Percent Change |
| Placebo | Percent Change From Baseline in Log-Transformed Serum 25-Hydroxyvitamin D at Month 24 | 0.57 Percent Change |
p-value: 0.37695% CI: [-10.04, 3.78]cLDA
Secondary
Percent Change From Baseline in Log-Transformed Serum Bone-Specific Alkaline Phosphatase at Month 24
Bone-Specific Alkaline Phosphatase (BSAP) is a biochemical marker of bone formation.
Time frame: Baseline and Month 24
Population: The population analyzed included all randomized, treated participants who had BSAP data at Baseline and Month 24 but excluded participants due to important protocol deviations that may have substantially affected the results such as use of concomitant medication, lack of study medication compliance, and medical history.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Log-Transformed Serum Bone-Specific Alkaline Phosphatase at Month 24 | 51.62 Percent change |
| Placebo | Percent Change From Baseline in Log-Transformed Serum Bone-Specific Alkaline Phosphatase at Month 24 | 40.65 Percent change |
p-value: 0.18695% CI: [-5.29, 27.22]cLDA
Secondary
Percent Change From Baseline in Log-Transformed Serum BSAP at Month 12
BSAP is a biochemical marker of bone formation.
Time frame: Baseline and Month 12
Population: The population analyzed included all randomized, treated participants who had BSAP data at Baseline and Month 12 but excluded participants due to important protocol deviations that may have substantially affected the results such as use of concomitant medication, lack of study medication compliance, and medical history.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Log-Transformed Serum BSAP at Month 12 | 30.91 Percent change |
| Placebo | Percent Change From Baseline in Log-Transformed Serum BSAP at Month 12 | 18.10 Percent change |
p-value: 0.01595% CI: [2.54, 23.1]cLDA
Secondary
Percent Change From Baseline in Log-Transformed Serum Calcium at Month 24
Serum calcium is an index of calcium homeostasis.
Time frame: Baseline and Month 24
Population: The population analyzed included all randomized, treated participants who had serum calcium data at Baseline and Month 24 but excluded participants due to important protocol deviations that may have substantially affected the results such as use of concomitant medication, lack of study medication compliance, and medical history.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Log-Transformed Serum Calcium at Month 24 | -2.40 Percent Change |
| Placebo | Percent Change From Baseline in Log-Transformed Serum Calcium at Month 24 | -2.51 Percent Change |
p-value: 0.84695% CI: [-0.95, 1.16]cLDA
Secondary
Percent Change From Baseline in Log-Transformed Serum C-Telopeptides of Type I Collagen (s-CTx) at Month 24
s-CTx is a biochemical marker of bone resorption.
Time frame: Baseline and Month 24
Population: The population analyzed included all randomized, treated participants who had s-CTx data at Baseline and Month 24 but excluded participants due to important protocol deviations that may have substantially affected the results such as use of concomitant medication, lack of study medication compliance, and medical history.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Log-Transformed Serum C-Telopeptides of Type I Collagen (s-CTx) at Month 24 | 93.86 Percent change |
| Placebo | Percent Change From Baseline in Log-Transformed Serum C-Telopeptides of Type I Collagen (s-CTx) at Month 24 | 83.70 Percent change |
p-value: 0.595% CI: [-19.39, 39.72]cLDA
Secondary
Percent Change From Baseline in Log-Transformed Serum N-terminal Propeptide of Type I Collagen at Month 12
s-P1NP is a biochemical marker of bone formation.
Time frame: Baseline and Month 12
Population: The population analyzed included all randomized, treated participants who had S-P1NP data at Baseline and Month 12 but excluded participants due to important protocol deviations that may have substantially affected the results such as use of concomitant medication, lack of study medication compliance, and medical history.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Log-Transformed Serum N-terminal Propeptide of Type I Collagen at Month 12 | 80.37 Percent change |
| Placebo | Percent Change From Baseline in Log-Transformed Serum N-terminal Propeptide of Type I Collagen at Month 12 | 56.37 Percent change |
p-value: 0.05995% CI: [-0.93, 48.94]cLDA
Secondary
Percent Change From Baseline in Log-Transformed Serum N-Terminal Propeptide of Type I Collagen at Month 24
Serum N-terminal propeptide of Type I collagen (s-P1NP) is a biochemical marker of bone formation.
Time frame: Baseline and Month 24
Population: The population analyzed included all randomized, treated participants who had S-P1NP data at Baseline and Month 24 but excluded participants due to important protocol deviations that may have substantially affected the results such as use of concomitant medication, lack of study medication compliance, and medical history.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Log-Transformed Serum N-Terminal Propeptide of Type I Collagen at Month 24 | 90.70 Percent change |
| Placebo | Percent Change From Baseline in Log-Transformed Serum N-Terminal Propeptide of Type I Collagen at Month 24 | 59.53 Percent change |
p-value: 0.01195% CI: [7.13, 55.21]cLDA
Secondary
Percent Change From Baseline in Log-Transformed Serum Parathyroid Hormone at Month 24
Serum parathyroid hormone (SPH) regulates calcium, phosphorus, and vitamin D levels in the blood.
Time frame: Baseline and Month 24
Population: The population analyzed included all randomized, treated participants who had SPH data at Baseline and Month 24 but excluded participants due to important protocol deviations that may have substantially affected the results such as use of concomitant medication, lack of study medication compliance, and medical history.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Log-Transformed Serum Parathyroid Hormone at Month 24 | 4.38 Percent Change |
| Placebo | Percent Change From Baseline in Log-Transformed Serum Parathyroid Hormone at Month 24 | 10.28 Percent Change |
p-value: 0.32695% CI: [-17.66, 5.85]cLDA
Secondary
Percent Change From Baseline in Log-Transformed Serum Phosphate at Month 24
Serum phosphate is an index of mineral homeostasis.
Time frame: Baseline and Month 24
Population: The population analyzed included all randomized, treated participants who had serum phosphate data at Baseline and Month 24 but excluded participants due to important protocol deviations that may have substantially affected the results such as use of concomitant medication, lack of study medication compliance, and medical history.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Log-Transformed Serum Phosphate at Month 24 | 2.37 Percent Change |
| Placebo | Percent Change From Baseline in Log-Transformed Serum Phosphate at Month 24 | 0.99 Percent Change |
p-value: 0.41395% CI: [-1.91, 4.67]cLDA
Secondary
Percent Change From Baseline in Log-Transformed u-NTx/Cr at Month 12
u-NTx/Cr is a biochemical marker of bone resorption.
Time frame: Baseline and Month 12
Population: The population analyzed included all randomized, treated participants who had u-NTx/Cr data at Baseline and Month 12 but excluded participants due to important protocol deviations that may have substantially affected the results such as use of concomitant medication, lack of study medication compliance, and medical history.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Log-Transformed u-NTx/Cr at Month 12 | -17.23 Percent change |
| Placebo | Percent Change From Baseline in Log-Transformed u-NTx/Cr at Month 12 | 29.06 Percent change |
p-value: <0.00195% CI: [-61.43, -31.15]cLDA
Secondary
Percent Change From Baseline in Log-Transformed Urine N-Telopeptides/Creatinine Ratio at Month 24
N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio (u-NTx/Cr) is a biochemical marker of bone resorption.
Time frame: Baseline and Month 24
Population: The population analyzed included all randomized, treated participants who had u-NTx/Cr data at Baseline and Month 24 but excluded participants due to important protocol deviations that may have substantially affected the results such as use of concomitant medication, lack of study medication compliance, and medical history.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Log-Transformed Urine N-Telopeptides/Creatinine Ratio at Month 24 | -15.55 Percent change |
| Placebo | Percent Change From Baseline in Log-Transformed Urine N-Telopeptides/Creatinine Ratio at Month 24 | 31.48 Percent change |
p-value: <0.00195% CI: [-62.4, -31.67]cLDA
Secondary
Percent Change From Baseline in Lumbar Spine BMD at Month 12
BMD at the lumbar spine was assessed by DXA at baseline and Month 12.
Time frame: Baseline and 12 Months
Population: The population analyzed included all randomized, treated participants who had lumbar spine BMD data at Baseline and Month 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Lumbar Spine BMD at Month 12 | 0.69 Percent Change |
| Placebo | Percent Change From Baseline in Lumbar Spine BMD at Month 12 | -0.12 Percent Change |
p-value: 0.10395% CI: [-0.16, 1.77]cLDA
Secondary
Percent Change From Baseline in Lumbar Spine BMD at Month 24
BMD at the lumbar spine was assessed by DXA at baseline and Month 24.
Time frame: Baseline and 24 Months
Population: The population analyzed included all randomized, treated participants who had lumbar spine BMD data at Baseline and Month 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Lumbar Spine BMD at Month 24 | 2.28 Percent Change |
| Placebo | Percent Change From Baseline in Lumbar Spine BMD at Month 24 | -0.30 Percent Change |
p-value: <0.00195% CI: [1.26, 3.89]cLDA
Secondary
Percent Change From Baseline in Total Hip BMD at Month 12
BMD at the total hip was assessed by DXA at baseline and Month 12.
Time frame: Baseline and 12 Months
Population: The population analyzed included all randomized, treated participants who had total hip BMD data at Baseline and Month 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Total Hip BMD at Month 12 | 0.26 Percent Change |
| Placebo | Percent Change From Baseline in Total Hip BMD at Month 12 | -0.80 Percent Change |
p-value: 0.02395% CI: [0.15, 1.98]cLDA
Secondary
Percent Change From Baseline in Total Hip BMD at Month 24
BMD at the total hip was assessed by DXA at baseline and Month 24.
Time frame: Baseline and 24 Months
Population: The population analyzed included all randomized, treated participants who had total hip BMD data at Baseline and Month 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Total Hip BMD at Month 24 | 0.83 Percent Change |
| Placebo | Percent Change From Baseline in Total Hip BMD at Month 24 | -1.87 Percent Change |
p-value: <0.00195% CI: [1.41, 4]cLDA
Secondary
Percent Change From Baseline in Trochanter BMD at Month 12
BMD at the trochanter was assessed by DXA at baseline and Month 12.
Time frame: Baseline and 12 Months
Population: The population analyzed included all randomized, treated participants who had trochanter BMD data at Baseline and Month 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Trochanter BMD at Month 12 | 0.86 Percent Change |
| Placebo | Percent Change From Baseline in Trochanter BMD at Month 12 | -0.14 Percent Change |
p-value: 0.14295% CI: [-0.34, 2.35]Constrained longitudinal data analysis
Secondary
Percent Change From Baseline in Trochanter BMD at Month 24
BMD at the trochanter was assessed by DXA at baseline and Month 24.
Time frame: Baseline and 24 Months
Population: The population analyzed included all randomized, treated participants who had trochanter BMD data at Baseline and Month 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg | Percent Change From Baseline in Trochanter BMD at Month 24 | 1.83 Percent Change |
| Placebo | Percent Change From Baseline in Trochanter BMD at Month 24 | -1.35 Percent Change |
p-value: 0.00295% CI: [1.19, 5.17]Constrained longitudinal data analysis