Osteoporosis
Conditions
Brief summary
The purpose of this study is to test the hypothesis that treatment with odanacatib will result in increased bone mineral density (BMD) compared to treatment with placebo. This study will also evaluate the safety and efficacy of odanacatib for male osteoporosis participants.
Detailed description
The original study was divided into two parts, with the primary analysis of endpoints to occur at 24 months and participants will then remain in the study for an additional 12 months (Part 2). Amendment 1 of the protocol removed the additional 12 month period and the Month 36 BMD analysis was deleted.
Interventions
DRUGOdanacatib
One 50 mg tablet once weekly
One 50 mg tablet once weekly
DIETARY_SUPPLEMENTVitamin D3
5600 IU of open-label Vitamin D3 once weekly
DIETARY_SUPPLEMENTCalcium carbonate
Sufficient amount of open-label calcium carbonate so that daily calcium intake from both dietary and supplementary sources in approximately 1200 mg
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
40 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
* Is a male between 40 and 95 years of age * Has osteoporosis * Has anatomy suitable for dual energy x-ray absorptiometry (DXA) scan of the lumbar spine and and hip * Is ambulatory
Exclusion criteria
* Is currently on oral bisphosphonates or other treatment for osteoporosis * Had previous hip fragility fracture and is a candidate for standard of care therapy * Has had a fragility fracture (vertebral or non-vertebral fractures indicating reduced bone strength) within 12 months * Has had more then one previous vertebral fracture * Has been diagnosed with metabolic bone disorder other than osteoporosis * Is Vitamin D deficient * Has a history of renal stones * Has active parathyroid disease * Has history of thyroid disease not well controlled by medication * Is diagnosed with secondary osteoporosis * Has a daily calcium intake of \<1,200 mg and is unwilling to take study prescribed supplements or increase dietary intake, such that his daily calcium intake is at least 1200 mg * Has a history of malignancy ≤5 years prior to signing informed consent * Has been diagnosed with hypogonadism due to causes that affect multiple organ and body systems
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Month 24 | Baseline and Month 24 | Lumbar spine BMD was assessed by dual energy X-ray absorptiometry (DXA) at Baseline and at Month 24. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to 24 months (plus 14 days) after first dose of study drug | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. |
| Number of Participants Who Discontinued Treatment Due to an AE | Up to 24 months after first dose of study drug | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Serum C-Telopeptides of Type 1 Collagen (s-CTx) at Month 24 | Baseline and Month 24 | Serum samples were collected to evaluate biochemical markers for s-CTx, which were measured at Baseline and at Month 24. |
| Percentage Change From Baseline in Urine Collagen N-Telopeptide/Creatinine Ratio (U-NTx/Cr) at Month 24 | Baseline and Month 24 | Urine samples were collected to evaluate biochemical markers for u-NTx/Cr, which were measured at Baseline and at Month 24. |
| Percentage Change From Baseline in Total Hip BMD at Month 24 | Baseline and Month 24 | Total hip BMD was assessed by DXA at Baseline and at Month 24. |
| Percentage Change From Baseline in Serum N-Terminal Propeptides of Type I Collagen (s-P1NP) at Month 24 | Baseline and Month 24 | Serum samples were collected to evaluate biochemical markers for s-P1NP, which were measured at Baseline and at Month 24. |
| Percentage Change From Baseline in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) at Month 24 | Baseline and Month 24 | Serum samples were collected to evaluate biochemical markers for s-BSAP, which were measured at Baseline and at Month 24. |
| Percentage Change From Baseline in Femoral Neck BMD at Month 24 | Baseline and Month 24 | Femoral Neck BMD was assessed by DXA at Baseline and at Month 24. |
| Percentage Change From Baseline in Trochanter BMD at Month 24 | Baseline and Month 24 | Trochanter BMD was assessed by DXA at Baseline and at Month 24. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Odanacatib 50 mg Once Weekly Participants received one Odanacatib 50 mg tablet once weekly. In addition, they received a weekly dose 5600 IU of open-label Vitamin D3 as well as a sufficient supply of open-label calcium carbonate so that their total daily calcium intake from both dietary and supplemental sources was approximately 1200 mg. | 147 |
| Placebo Once Weekly Participants received one Placebo tablet once weekly. In addition, they received a weekly dose 5600 IU of open-label Vitamin D3 as well as a sufficient supply of open-label calcium carbonate so that their total daily calcium intake from both dietary and supplemental sources was approximately 1200 mg. | 147 |
| Total | 294 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 7 |
| Overall Study | Excessive Bone Loss | 0 | 4 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Physician Decision | 1 | 3 |
| Overall Study | Protocol Violation | 0 | 4 |
| Overall Study | Withdrawal by Subject | 10 | 11 |
Baseline characteristics
| Characteristic | Odanacatib 50 mg Once Weekly | Placebo Once Weekly | Total |
|---|---|---|---|
| Age, Continuous | 68.9 years STANDARD_DEVIATION 8.2 | 68.7 years STANDARD_DEVIATION 7.7 | 68.8 years STANDARD_DEVIATION 7.9 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 147 Participants | 147 Participants | 294 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 146 | 44 / 146 |
| serious Total, serious adverse events | 24 / 146 | 24 / 146 |
Outcome results
Primary
Number of Participants Who Discontinued Treatment Due to an AE
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Time frame: Up to 24 months after first dose of study drug
Population: All randomized participants who took at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Odanacatib 50 mg Once Weekly | Number of Participants Who Discontinued Treatment Due to an AE | 5 Participants |
| Placebo Once Weekly | Number of Participants Who Discontinued Treatment Due to an AE | 6 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (AE)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Time frame: Up to 24 months (plus 14 days) after first dose of study drug
Population: All randomized participants who took at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Odanacatib 50 mg Once Weekly | Number of Participants Who Experienced an Adverse Event (AE) | 113 Participants |
| Placebo Once Weekly | Number of Participants Who Experienced an Adverse Event (AE) | 114 Participants |
Primary
Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Month 24
Lumbar spine BMD was assessed by dual energy X-ray absorptiometry (DXA) at Baseline and at Month 24.
Time frame: Baseline and Month 24
Population: All randomized participants who took at least one dose of blinded study treatment and had available lumbar spine BMD data for Baseline and Month 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg Once Weekly | Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Month 24 | 6.86 Percentage change |
| Placebo Once Weekly | Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Month 24 | 1.27 Percentage change |
Comparison: A constrained full likelihood longitudinal data analysis (cLDA) method was used for this statistical analysis. The cLDA model included the baseline measurement and all post-baseline percent changes from baseline in the response vector, with fixed effects for treatment, time, geographic region, machine type and treatment-by-time interaction, geographic region-by-time interaction, and machine type-by-time interaction.p-value: <0.00195% CI: [4.48, 6.7]cLDA
Secondary
Percentage Change From Baseline in Femoral Neck BMD at Month 24
Femoral Neck BMD was assessed by DXA at Baseline and at Month 24.
Time frame: Baseline and Month 24
Population: All randomized participants who took at least one dose of blinded study treatment and had available femoral neck BMD data for Baseline and Month 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg Once Weekly | Percentage Change From Baseline in Femoral Neck BMD at Month 24 | 1.69 Percentage change |
| Placebo Once Weekly | Percentage Change From Baseline in Femoral Neck BMD at Month 24 | 0 Percentage change |
Comparison: A cLDA method was used for this statistical analysis. The cLDA model included the baseline measurement and all post-baseline percent changes from baseline in the response vector, with fixed effects for treatment, time, geographic region, machine type and treatment-by-time interaction, geographic region-by-time interaction, and machine type-by-time interaction.p-value: =0.00895% CI: [0.45, 2.93]cLDA
Secondary
Percentage Change From Baseline in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) at Month 24
Serum samples were collected to evaluate biochemical markers for s-BSAP, which were measured at Baseline and at Month 24.
Time frame: Baseline and Month 24
Population: All randomized participants who had no important deviations from the protocol that may have substantially affected the results, and had available s-BSAP data for Baseline and Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg Once Weekly | Percentage Change From Baseline in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) at Month 24 | -5.28 Percentage change |
| Placebo Once Weekly | Percentage Change From Baseline in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) at Month 24 | 2.66 Percentage change |
Comparison: A cLDA method was used for this statistical analysis. The cLDA model included the baseline measurement and all post-baseline percent changes from baseline in the response vector, with fixed effects for treatment, time, geographic region, machine type and treatment-by-time interaction, geographic region-by-time interaction, and machine type-by-time interaction.p-value: =0.01995% CI: [-14.58, -1.31]cLDA
Secondary
Percentage Change From Baseline in Serum C-Telopeptides of Type 1 Collagen (s-CTx) at Month 24
Serum samples were collected to evaluate biochemical markers for s-CTx, which were measured at Baseline and at Month 24.
Time frame: Baseline and Month 24
Population: All randomized participants who had no important deviations from the protocol that may have substantially affected the results, and had available s-CTx data for Baseline and Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg Once Weekly | Percentage Change From Baseline in Serum C-Telopeptides of Type 1 Collagen (s-CTx) at Month 24 | -20.07 Percentage change |
| Placebo Once Weekly | Percentage Change From Baseline in Serum C-Telopeptides of Type 1 Collagen (s-CTx) at Month 24 | 56.51 Percentage change |
Comparison: A cLDA method was used for this statistical analysis. The cLDA model included the baseline measurement and all post-baseline percent changes from baseline in the response vector, with fixed effects for treatment, time, geographic region, machine type and treatment-by-time interaction, geographic region-by-time interaction, and machine type-by-time interaction.p-value: <0.00195% CI: [-92.56, -60.61]cLDA
Secondary
Percentage Change From Baseline in Serum N-Terminal Propeptides of Type I Collagen (s-P1NP) at Month 24
Serum samples were collected to evaluate biochemical markers for s-P1NP, which were measured at Baseline and at Month 24.
Time frame: Baseline and Month 24
Population: All randomized participants who had no important deviations from the protocol that may have substantially affected the results, and had available s-P1NP data for Baseline and Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg Once Weekly | Percentage Change From Baseline in Serum N-Terminal Propeptides of Type I Collagen (s-P1NP) at Month 24 | -10.94 Percentage change |
| Placebo Once Weekly | Percentage Change From Baseline in Serum N-Terminal Propeptides of Type I Collagen (s-P1NP) at Month 24 | 5.06 Percentage change |
Comparison: A cLDA method was used for this statistical analysis. The cLDA model included the baseline measurement and all post-baseline percent changes from baseline in the response vector, with fixed effects for treatment, time, geographic region, machine type and treatment-by-time interaction, geographic region-by-time interaction, and machine type-by-time interaction.p-value: =0.00195% CI: [-25.74, -6.27]cLDA
Secondary
Percentage Change From Baseline in Total Hip BMD at Month 24
Total hip BMD was assessed by DXA at Baseline and at Month 24.
Time frame: Baseline and Month 24
Population: All randomized participants who took at least one dose of blinded study treatment and had available total hip BMD data for Baseline and Month 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg Once Weekly | Percentage Change From Baseline in Total Hip BMD at Month 24 | 1.91 Percentage change |
| Placebo Once Weekly | Percentage Change From Baseline in Total Hip BMD at Month 24 | -0.11 Percentage change |
Comparison: A cLDA method was used for this statistical analysis. The cLDA model included the baseline measurement and all post-baseline percent changes from baseline in the response vector, with fixed effects for treatment, time, geographic region, machine type and treatment-by-time interaction, geographic region-by-time interaction, and machine type-by-time interaction.p-value: <0.00195% CI: [1.27, 2.77]cLDA
Secondary
Percentage Change From Baseline in Trochanter BMD at Month 24
Trochanter BMD was assessed by DXA at Baseline and at Month 24.
Time frame: Baseline and Month 24
Population: All randomized participants who took at least one dose of blinded study treatment and had available trochanter BMD data for Baseline and Month 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg Once Weekly | Percentage Change From Baseline in Trochanter BMD at Month 24 | 2.77 Percentage change |
| Placebo Once Weekly | Percentage Change From Baseline in Trochanter BMD at Month 24 | 0.66 Percentage change |
Comparison: A cLDA method was used for this statistical analysis. The cLDA model included the baseline measurement and all post-baseline percent changes from baseline in the response vector, with fixed effects for treatment, time, geographic region, machine type and treatment-by-time interaction, geographic region-by-time interaction, and machine type-by-time interaction.p-value: <0.00195% CI: [0.93, 3.3]cLDA
Secondary
Percentage Change From Baseline in Urine Collagen N-Telopeptide/Creatinine Ratio (U-NTx/Cr) at Month 24
Urine samples were collected to evaluate biochemical markers for u-NTx/Cr, which were measured at Baseline and at Month 24.
Time frame: Baseline and Month 24
Population: All randomized participants who had no important deviations from the protocol that may have substantially affected the results, and had available U-NTx/Cr data for Baseline and Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Odanacatib 50 mg Once Weekly | Percentage Change From Baseline in Urine Collagen N-Telopeptide/Creatinine Ratio (U-NTx/Cr) at Month 24 | -61.43 Percentage change |
| Placebo Once Weekly | Percentage Change From Baseline in Urine Collagen N-Telopeptide/Creatinine Ratio (U-NTx/Cr) at Month 24 | 6.65 Percentage change |
Comparison: A cLDA method was used for this statistical analysis. The cLDA model included the baseline measurement and all post-baseline percent changes from baseline in the response vector, with fixed effects for treatment, time, geographic region, machine type and treatment-by-time interaction, geographic region-by-time interaction, and machine type-by-time interaction.p-value: <0.00195% CI: [-78.1, -58.06]cLDA