Osteoporosis
Conditions
Keywords
Osteoporosis, Postmenopausal, MK-5442
Brief summary
The purpose of this study was to identify an appropriate dose of MK-5442 that produced an osteoanabolic effect without causing hypercalcemia in postmenopausal women with osteoporosis.
Detailed description
Amendment 4 of the protocol changed the duration of the study from 2 years to 6 months.
Interventions
DRUGMK-5442
MK-5442 2.5 mg, 5 mg, 7.5 mg, 10 mg, or 15 mg tablet once daily for at least 6 months.
DRUGPlacebo
Dose-matched oral placebo to MK-5442
DIETARY_SUPPLEMENTVitamin D3
Vitamin D3, two 400 IU tablets daily throughout the study.
DIETARY_SUPPLEMENTCalcium carbonate
Participants who had a calcium intake of less than 1200 mg/day at baseline received a daily 500 mg calcium supplement throughout the study.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Postmenopausal for at least 5 years * No history of fragility fracture, unless participant is not willing to take marketed osteoporosis therapy or is not a candidate for marketed osteoporosis therapy * Agrees not to use medications for osteoporosis except medications associated with the study * Areal bone mineral density (BMD) T-score \<-2.5 at one or more of the following 4 BMD sites: total hip, femoral neck, trochanter, or lumbar spine and is ≥ -3.5 at all 4 BMD sites. Participants unwilling to take or ineligible for marketed osteoporosis therapy may have one or more areal BMD T-scores of \< -3.5
Exclusion criteria
* Unable to undergo dual-energy X-ray absorptiometry (DXA) scan due to obesity (ie, weight \>250 lbs) * Use of oral bisphosphonates in the 6 months prior to study screening, for more than 3 months in the past 2 years, or lifetime use of more than 6 months * Use of intravenous bisphosphonates, strontium, or growth hormone at any time * Use of phenytoin or heparin within 2 weeks prior to Visit 1; use of raloxifene within 6 months prior to Visit 1 * Use of pioglitazone or rosiglitazone at study screening * Use of estrogen ± progestin, in any form other than vaginal or topical application, for 6 months prior to Study Visit 1 * Prior total thyroidectomy * Human immunodeficiency virus (HIV)- positive or acquired immune deficiency syndrome (AIDS)-related illness * History of malignant cancer within 5 years of study screening, except for certain skin or cervical cancers * History of Paget's disease and/or kidney stones * An active user of any illicit drug * History of or active alcohol abuse * Participated in an investigational drug study within the past 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares (LS) Mean Percent Change From Baseline to Month 6 in Lumbar Spine Areal Bone Mineral Density (aBMD) | Baseline (BL) and Month 6 | Dual Energy X-ray Absorptiometry (DXA) was used to assess and measure aBMD of the lumbar spine. Areal BMD was measured as areal density using units of gram (gm) of tissue /centimeter of tissue squared (cm\^2). |
| Percentage of Participants With Total Serum Calcium Levels Outside the Pre-defined Limits of Change | Baseline through Month 6 | Normal serum calcium level is 8-10 mg/dL (2-2.5 mmol/L) with some interlaboratory variation in the reference range, and hypercalcemia is defined as a serum calcium level greater than 10.5 mg/dL (\>2.5 mmol/L). Based on these references, ≥10.6 mg/dL was predefined in this study as the cut-off for the normal limits of change. Participants with calcium levels ≥10.6 mg/dL were considered as having a Tier 1 safety event. |
| Percentage of Participants With Albumin-Corrected Calcium Levels Outside the Pre-defined Limits of Change | Baseline through Month 6 | Albumin-Corrected Calcium = (\[4 - plasma albumin in g/dL\] × 0.8 + serum calcium). ≥10.6 mg/dL was predefined in this study as the cut-off for the normal limits of change. Participants with albumin-corrected calcium levels ≥10.6 mg/dL were considered as having a Tier 1 safety event. |
| Percentage of Participants With Kidney Stones | Baseline through Month 6 | Evidence of kidney stone(s) was considered an event of interest and was prespecified as a Tier 1 safety event. |
| Percentage of Participants With Bone Neoplasms | Baseline through Month 6 | Evidence of bone neoplasm(s) was considered an event of interest and was prespecified as a Tier 1 safety event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Hip | Baseline and Month 6 | Quantitative computed tomography (QCT) technology was used to assess and measure bone mineral content volumetrically (ie, in grams of tissue per centimeter of tissue cubed). |
| LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Lumbar Spine | Baseline and Month 6 | Quantitative computed tomography (QCT) technology was used at baseline and periodically through out the study to assess and measure bone mineral content volumetrically (ie, in grams of tissue per centimeter of tissue cubed). |
| LS Mean Percent Change From Baseline to Month 6 in the Ratio of Urinary N-Telopeptides of Type I Collagen to Creatinine (u-NTx/Cr) | Baseline and Month 6 | The ratio of u-NTx to Cr is a biomarker for bone resorption. It is measured in the serum in units of nanomoles (nm) of bone collagen equivalents (BCE)/millimoles of creatinine (Cr). |
| LS Mean Percent Change From Baseline to Month 6 in Total Hip aBMD | Baseline and Month 6 | DXA was used to assess and measure aBMD of the total hip. Areal BMD was measured as areal density using units of gram (gm) of tissue /centimeter of tissue squared (cm\^2). |
| LS Mean Percent Change From Baseline to Month 6 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) | Baseline and Month 6 | Bone Specific Alkaline Phosphatase is a biomarker of bone formation and is measured in units of microgram (μg)/liter (L). |
| LS Mean Percent Change From Baseline to Month 6 in Serum Procollagen Type I N-Terminal Propeptide (P1NP) | Baseline to Month 6 | Measurement of P1NP appears to be a sensitive marker of bone formation rate in the assessment of osteoporosis. |
| LS Mean Percent Change From Baseline to Month 6 in Serum Osteocalcin | Baseline and Month 6 | Serum osteocalcin is a biomarker of bone formation and is measured using units of nanograms (ng) / milliliter (mL). |
| LS Mean Percent Change From Baseline to Month 6 in Serum C-Terminal Telopeptide Collagen I (s-CTx) | Baseline to Month 6 | C-Terminal Telopeptide Collagen I is used as a serum-marker of bone resorption in the assessment of osteoporosis. |
| LS Mean Percent Change From Baseline to Month 6 in Femoral Neck aBMD | Baseline and Month 6 | DXA was used to assess and measure aBMD of the femoral neck. Areal BMD was measured as areal density using units of gram (gm) of tissue /centimeter of tissue squared (cm\^2). |
| LS Mean Percent Change From Baseline to Month 6 in Trochanter aBMD | Baseline and Month 6 | DXA was used to assess and measure aBMD of the trochanter. Areal BMD was measured as areal density using units of gram (gm) of tissue /centimeter of tissue squared (cm\^2). |
| LS Mean Percent Change From Baseline to Month 6 in Total Body aBMD | Baseline and Month 6 | DXA was used to assess and measure aBMD of the total body. Areal BMD was measured as areal density using units of gram (gm) of tissue /centimeter of tissue squared (cm\^2). |
| LS Mean Percent Change From Baseline to Month 6 in Distal One-third Forearm Areal BMD | Baseline and Month 6 | DXA was used to assess and measure aBMD of the distal 1/3 forearm. Areal BMD was measured as areal density using units of gram (gm) of tissue /centimeter of tissue squared (cm\^2). |
Participant flow
Pre-assignment details
383 participants were randomized on study and 380 participants were treated on study.
Participants by arm
| Arm | Count |
|---|---|
| MK-5442 2.5 mg Following a 2-week open-label placebo run-in, participants received a daily oral dose of 2.5 mg of MK-5442 for a duration of at least 6 months. | 64 |
| MK-5442 5 mg Following a 2-week open-label placebo run-in, participants received a daily oral dose of 5 mg of MK-5442 for a duration of at least 6 months. | 63 |
| MK-5442 7.5 mg Following a 2-week open-label placebo run-in, participants received a daily oral dose of 7.5 mg of MK-5442 for a duration of at least 6 months. | 64 |
| MK-5442 10 mg Following a 2-week open-label placebo run-in, participants received a daily oral dose of 10 mg of MK-5442 for a duration of at least 6 months. | 64 |
| MK-5442 15 mg Following a 2-week open-label placebo run-in, participants received a daily oral dose of 15 mg of MK-5442 for a duration of at least 6 months. | 64 |
| Placebo Following a 2-week open-label placebo run-in, participants received a daily oral dose of placebo dose-matched to MK-5442 for a duration of at least 6 months. | 64 |
| Total | 383 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 3 | 2 | 4 | 3 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 2 | 1 | 5 | 4 | 2 | 2 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Progressive Disease | 1 | 1 | 0 | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 3 | 4 | 0 | 3 | 3 | 2 |
| Overall Study | Study Terminated by Sponsor | 50 | 46 | 52 | 50 | 49 | 49 |
| Overall Study | Withdrawal by Subject | 5 | 6 | 4 | 5 | 5 | 7 |
Baseline characteristics
| Characteristic | MK-5442 2.5 mg | MK-5442 5 mg | MK-5442 7.5 mg | MK-5442 10 mg | MK-5442 15 mg | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.7 years STANDARD_DEVIATION 6.3 | 67.3 years STANDARD_DEVIATION 6.5 | 67.4 years STANDARD_DEVIATION 6 | 67.8 years STANDARD_DEVIATION 6.4 | 66.5 years STANDARD_DEVIATION 5.4 | 67.6 years STANDARD_DEVIATION 6.7 | 67.2 years STANDARD_DEVIATION 6.2 |
| Sex: Female, Male Female | 64 Participants | 63 Participants | 64 Participants | 64 Participants | 64 Participants | 64 Participants | 383 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 64 | 24 / 62 | 15 / 64 | 28 / 64 | 18 / 63 | 26 / 63 |
| serious Total, serious adverse events | 3 / 64 | 0 / 62 | 4 / 64 | 5 / 64 | 4 / 63 | 3 / 63 |
Outcome results
Primary
Least Squares (LS) Mean Percent Change From Baseline to Month 6 in Lumbar Spine Areal Bone Mineral Density (aBMD)
Dual Energy X-ray Absorptiometry (DXA) was used to assess and measure aBMD of the lumbar spine. Areal BMD was measured as areal density using units of gram (gm) of tissue /centimeter of tissue squared (cm\^2).
Time frame: Baseline (BL) and Month 6
Population: Full Analysis Set (FAS); participants who received at least one dose of study treatment, had post-randomization data subsequent to at least one dose of study treatment, and who had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-5442 2.5 mg | Least Squares (LS) Mean Percent Change From Baseline to Month 6 in Lumbar Spine Areal Bone Mineral Density (aBMD) | 0.74 percent change |
| MK-5442 5 mg | Least Squares (LS) Mean Percent Change From Baseline to Month 6 in Lumbar Spine Areal Bone Mineral Density (aBMD) | 1.50 percent change |
| MK-5442 7.5 mg | Least Squares (LS) Mean Percent Change From Baseline to Month 6 in Lumbar Spine Areal Bone Mineral Density (aBMD) | 0.92 percent change |
| MK-5442 10 mg | Least Squares (LS) Mean Percent Change From Baseline to Month 6 in Lumbar Spine Areal Bone Mineral Density (aBMD) | 1.69 percent change |
| MK-5442 15 mg | Least Squares (LS) Mean Percent Change From Baseline to Month 6 in Lumbar Spine Areal Bone Mineral Density (aBMD) | 1.13 percent change |
| Placebo | Least Squares (LS) Mean Percent Change From Baseline to Month 6 in Lumbar Spine Areal Bone Mineral Density (aBMD) | 0.57 percent change |
p-value: 0.74995% CI: [-1.04, 2.16]Longitudinal Data Analysis Model
p-value: 0.33395% CI: [-0.6, 2.83]Longitudinal Data Analysis Model
p-value: 0.82395% CI: [-1.14, 1.84]Longitudinal Data Analysis Model
p-value: 0.45795% CI: [-0.75, 2.61]Longitudinal Data Analysis Model
p-value: 0.82395% CI: [-1.17, 1.5]Longitudinal Data Analysis Model
Primary
Percentage of Participants With Albumin-Corrected Calcium Levels Outside the Pre-defined Limits of Change
Albumin-Corrected Calcium = (\[4 - plasma albumin in g/dL\] × 0.8 + serum calcium). ≥10.6 mg/dL was predefined in this study as the cut-off for the normal limits of change. Participants with albumin-corrected calcium levels ≥10.6 mg/dL were considered as having a Tier 1 safety event.
Time frame: Baseline through Month 6
Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment. 3 randomized participants did not receive treatment and were not included in the APaT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-5442 2.5 mg | Percentage of Participants With Albumin-Corrected Calcium Levels Outside the Pre-defined Limits of Change | 0.0 Percentage of participants |
| MK-5442 5 mg | Percentage of Participants With Albumin-Corrected Calcium Levels Outside the Pre-defined Limits of Change | 9.7 Percentage of participants |
| MK-5442 7.5 mg | Percentage of Participants With Albumin-Corrected Calcium Levels Outside the Pre-defined Limits of Change | 18.8 Percentage of participants |
| MK-5442 10 mg | Percentage of Participants With Albumin-Corrected Calcium Levels Outside the Pre-defined Limits of Change | 37.5 Percentage of participants |
| MK-5442 15 mg | Percentage of Participants With Albumin-Corrected Calcium Levels Outside the Pre-defined Limits of Change | 49.2 Percentage of participants |
| Placebo | Percentage of Participants With Albumin-Corrected Calcium Levels Outside the Pre-defined Limits of Change | 1.6 Percentage of participants |
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: <0.00195% CI: [34.9, 60]Miettinen and Nurminen Method
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: <0.00195% CI: [24.1, 48.5]Miettinen and Nurminen Method
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: 0.00195% CI: [7.7, 28.7]Miettinen and Nurminen Method
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: 0.0595% CI: [0, 18.2]Miettinen and Nurminen Method
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: 0.31395% CI: [-8.5, 4.2]Miettinen and Nurminen Method
Primary
Percentage of Participants With Bone Neoplasms
Evidence of bone neoplasm(s) was considered an event of interest and was prespecified as a Tier 1 safety event.
Time frame: Baseline through Month 6
Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment. 3 randomized participants did not receive treatment and were not included in the APaT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-5442 2.5 mg | Percentage of Participants With Bone Neoplasms | 0.0 Percentage of participants |
| MK-5442 5 mg | Percentage of Participants With Bone Neoplasms | 0.0 Percentage of participants |
| MK-5442 7.5 mg | Percentage of Participants With Bone Neoplasms | 0.0 Percentage of participants |
| MK-5442 10 mg | Percentage of Participants With Bone Neoplasms | 0.0 Percentage of participants |
| MK-5442 15 mg | Percentage of Participants With Bone Neoplasms | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Bone Neoplasms | 0.0 Percentage of participants |
Primary
Percentage of Participants With Kidney Stones
Evidence of kidney stone(s) was considered an event of interest and was prespecified as a Tier 1 safety event.
Time frame: Baseline through Month 6
Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment. 3 randomized participants did not receive treatment and were not included in the APaT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-5442 2.5 mg | Percentage of Participants With Kidney Stones | 1.6 Percentage of participants |
| MK-5442 5 mg | Percentage of Participants With Kidney Stones | 1.6 Percentage of participants |
| MK-5442 7.5 mg | Percentage of Participants With Kidney Stones | 0.0 Percentage of participants |
| MK-5442 10 mg | Percentage of Participants With Kidney Stones | 0.0 Percentage of participants |
| MK-5442 15 mg | Percentage of Participants With Kidney Stones | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Kidney Stones | 0.0 Percentage of participants |
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: >0.99995% CI: [-5.8, 5.8]Miettinen and Nurminen Method
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: >0.99995% CI: [-5.8, 5.7]Miettinen and Nurminen Method
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: >0.99995% CI: [-5.8, 5.7]Miettinen and Nurminen Method
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: 0.31395% CI: [-4.2, 8.6]Miettinen and Nurminen Method
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: 0.32195% CI: [-4.3, 8.4]Miettinen and Nurminen Method
Primary
Percentage of Participants With Total Serum Calcium Levels Outside the Pre-defined Limits of Change
Normal serum calcium level is 8-10 mg/dL (2-2.5 mmol/L) with some interlaboratory variation in the reference range, and hypercalcemia is defined as a serum calcium level greater than 10.5 mg/dL (\>2.5 mmol/L). Based on these references, ≥10.6 mg/dL was predefined in this study as the cut-off for the normal limits of change. Participants with calcium levels ≥10.6 mg/dL were considered as having a Tier 1 safety event.
Time frame: Baseline through Month 6
Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment. 3 randomized participants did not receive treatment and were not included in the APaT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-5442 2.5 mg | Percentage of Participants With Total Serum Calcium Levels Outside the Pre-defined Limits of Change | 7.8 Percentage of participants |
| MK-5442 5 mg | Percentage of Participants With Total Serum Calcium Levels Outside the Pre-defined Limits of Change | 32.3 Percentage of participants |
| MK-5442 7.5 mg | Percentage of Participants With Total Serum Calcium Levels Outside the Pre-defined Limits of Change | 32.8 Percentage of participants |
| MK-5442 10 mg | Percentage of Participants With Total Serum Calcium Levels Outside the Pre-defined Limits of Change | 56.3 Percentage of participants |
| MK-5442 15 mg | Percentage of Participants With Total Serum Calcium Levels Outside the Pre-defined Limits of Change | 73.0 Percentage of participants |
| Placebo | Percentage of Participants With Total Serum Calcium Levels Outside the Pre-defined Limits of Change | 3.2 Percentage of participants |
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: <0.00195% CI: [56.5, 80]Miettinen and Nurminen Method
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: <0.00195% CI: [39.6, 65.2]Miettinen and Nurminen Method
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: <0.00195% CI: [17.6, 42.4]Miettinen and Nurminen Method
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: <0.00195% CI: [17, 42]Miettinen and Nurminen Method
Comparison: The Miettinen and Nurminen Method was used to estimate the treatment differences between the active dose group and the placebo group by comparing the percentage of participants in the active dose group with the event vs. the percentage of participants in the placebo group with the event. An associated p-value and 95% confidence interval were calculated for this difference.p-value: 0.25495% CI: [-4.1, 14.4]Miettinen and Nurminen Method
Secondary
LS Mean Percent Change From Baseline to Month 6 in Distal One-third Forearm Areal BMD
DXA was used to assess and measure aBMD of the distal 1/3 forearm. Areal BMD was measured as areal density using units of gram (gm) of tissue /centimeter of tissue squared (cm\^2).
Time frame: Baseline and Month 6
Population: Full Analysis Set (FAS); participants who received at least one dose of study treatment, had post-randomization data subsequent to at least one dose of study treatment, and who had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-5442 2.5 mg | LS Mean Percent Change From Baseline to Month 6 in Distal One-third Forearm Areal BMD | -0.47 percent change |
| MK-5442 5 mg | LS Mean Percent Change From Baseline to Month 6 in Distal One-third Forearm Areal BMD | -0.32 percent change |
| MK-5442 7.5 mg | LS Mean Percent Change From Baseline to Month 6 in Distal One-third Forearm Areal BMD | 0.44 percent change |
| MK-5442 10 mg | LS Mean Percent Change From Baseline to Month 6 in Distal One-third Forearm Areal BMD | -0.49 percent change |
| MK-5442 15 mg | LS Mean Percent Change From Baseline to Month 6 in Distal One-third Forearm Areal BMD | -0.56 percent change |
| Placebo | LS Mean Percent Change From Baseline to Month 6 in Distal One-third Forearm Areal BMD | -0.21 percent change |
p-value: 0.96195% CI: [-2, 1.31]Longitudinal Data Analysis Model
p-value: 0.96195% CI: [-1.9, 1.34]Longitudinal Data Analysis Model
p-value: 0.77895% CI: [-1.01, 2.33]Longitudinal Data Analysis Model
p-value: 0.96195% CI: [-1.45, 1.24]Longitudinal Data Analysis Model
p-value: 0.96195% CI: [-1.77, 1.26]Longitudinal Data Analysis Model
Secondary
LS Mean Percent Change From Baseline to Month 6 in Femoral Neck aBMD
DXA was used to assess and measure aBMD of the femoral neck. Areal BMD was measured as areal density using units of gram (gm) of tissue /centimeter of tissue squared (cm\^2).
Time frame: Baseline and Month 6
Population: Full Analysis Set (FAS); participants who received at least one dose of study treatment, had post-randomization data subsequent to at least one dose of study treatment, and who had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-5442 2.5 mg | LS Mean Percent Change From Baseline to Month 6 in Femoral Neck aBMD | 1.23 percent change |
| MK-5442 5 mg | LS Mean Percent Change From Baseline to Month 6 in Femoral Neck aBMD | -0.52 percent change |
| MK-5442 7.5 mg | LS Mean Percent Change From Baseline to Month 6 in Femoral Neck aBMD | 0.12 percent change |
| MK-5442 10 mg | LS Mean Percent Change From Baseline to Month 6 in Femoral Neck aBMD | -0.20 percent change |
| MK-5442 15 mg | LS Mean Percent Change From Baseline to Month 6 in Femoral Neck aBMD | 0.54 percent change |
| Placebo | LS Mean Percent Change From Baseline to Month 6 in Femoral Neck aBMD | -0.04 percent change |
p-value: 0.84995% CI: [-1.22, 2.37]Longitudinal Data Analysis Model
p-value: 0.96495% CI: [-1.79, 1.47]Longitudinal Data Analysis Model
p-value: 0.96495% CI: [-1.27, 1.59]Longitudinal Data Analysis Model
p-value: 0.85595% CI: [-2.23, 1.27]Longitudinal Data Analysis Model
p-value: 0.28795% CI: [-0.58, 3.12]Longitudinal Data Analysis Model
Secondary
LS Mean Percent Change From Baseline to Month 6 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP)
Bone Specific Alkaline Phosphatase is a biomarker of bone formation and is measured in units of microgram (μg)/liter (L).
Time frame: Baseline and Month 6
Population: Per Protocol population; defined as the subset of the APaT population that excluded participants based on critical protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-5442 2.5 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) | -0.60 percent change |
| MK-5442 5 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) | 0.26 percent change |
| MK-5442 7.5 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) | 4.39 percent change |
| MK-5442 10 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) | 17.33 percent change |
| MK-5442 15 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) | 13.13 percent change |
| Placebo | LS Mean Percent Change From Baseline to Month 6 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) | -6.05 percent change |
p-value: <0.00195% CI: [7.42, 31.02]Longitudinal Data Analysis Model
p-value: <0.00195% CI: [11.02, 35.82]Longitudinal Data Analysis Model
p-value: 0.06195% CI: [-0.37, 21.3]Longitudinal Data Analysis Model
p-value: 0.28395% CI: [-3.81, 16.45]Longitudinal Data Analysis Model
p-value: 0.28395% CI: [-3.39, 14.31]Longitudinal Data Analysis Model
Secondary
LS Mean Percent Change From Baseline to Month 6 in Serum C-Terminal Telopeptide Collagen I (s-CTx)
C-Terminal Telopeptide Collagen I is used as a serum-marker of bone resorption in the assessment of osteoporosis.
Time frame: Baseline to Month 6
Population: Per Protocol population; defined as the subset of the APaT population that excluded participants based on critical protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-5442 2.5 mg | LS Mean Percent Change From Baseline to Month 6 in Serum C-Terminal Telopeptide Collagen I (s-CTx) | -15.39 percent change |
| MK-5442 5 mg | LS Mean Percent Change From Baseline to Month 6 in Serum C-Terminal Telopeptide Collagen I (s-CTx) | -5.87 percent change |
| MK-5442 7.5 mg | LS Mean Percent Change From Baseline to Month 6 in Serum C-Terminal Telopeptide Collagen I (s-CTx) | -4.93 percent change |
| MK-5442 10 mg | LS Mean Percent Change From Baseline to Month 6 in Serum C-Terminal Telopeptide Collagen I (s-CTx) | 5.68 percent change |
| MK-5442 15 mg | LS Mean Percent Change From Baseline to Month 6 in Serum C-Terminal Telopeptide Collagen I (s-CTx) | 19.37 percent change |
| Placebo | LS Mean Percent Change From Baseline to Month 6 in Serum C-Terminal Telopeptide Collagen I (s-CTx) | -14.89 percent change |
p-value: 0.30795% CI: [-5.69, 25.7]Longitudinal Data Analysis
p-value: 0.30795% CI: [-5.85, 23.95]Longitudinal Data Analysis
p-value: 0.93795% CI: [-12.92, 11.92]Longitudinal Data Analysis
p-value: <0.00195% CI: [15.27, 53.56]Longitudinal Data Analysis
p-value: 0.01495% CI: [3.28, 38.02]Longitudinal Data Analysis
Secondary
LS Mean Percent Change From Baseline to Month 6 in Serum Osteocalcin
Serum osteocalcin is a biomarker of bone formation and is measured using units of nanograms (ng) / milliliter (mL).
Time frame: Baseline and Month 6
Population: Per Protocol population; defined as the subset of the APaT population that excluded participants based on critical protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-5442 2.5 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Osteocalcin | -11.61 percent change |
| MK-5442 5 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Osteocalcin | -2.75 percent change |
| MK-5442 7.5 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Osteocalcin | 9.18 percent change |
| MK-5442 10 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Osteocalcin | 25.79 percent change |
| MK-5442 15 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Osteocalcin | 37.43 percent change |
| Placebo | LS Mean Percent Change From Baseline to Month 6 in Serum Osteocalcin | -15.62 percent change |
p-value: <0.00195% CI: [37.83, 68.53]Longitudinal Data Analysis Model
p-value: <0.00195% CI: [27.36, 55.65]Longitudinal Data Analysis Model
p-value: <0.00195% CI: [12.39, 37.33]Longitudinal Data Analysis Model
p-value: 0.0295% CI: [1.73, 24.06]Longitudinal Data Analysis Model
p-value: 0.39795% CI: [-5.31, 13.36]Longitudinal Data Analysis Model
Secondary
LS Mean Percent Change From Baseline to Month 6 in Serum Procollagen Type I N-Terminal Propeptide (P1NP)
Measurement of P1NP appears to be a sensitive marker of bone formation rate in the assessment of osteoporosis.
Time frame: Baseline to Month 6
Population: The 'Per Protocol' population was used for this analysis. The Per-Protocol population was defined as a subset population that excluded participants based on critical protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-5442 2.5 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Procollagen Type I N-Terminal Propeptide (P1NP) | -9.97 percent change |
| MK-5442 5 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Procollagen Type I N-Terminal Propeptide (P1NP) | -9.76 percent change |
| MK-5442 7.5 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Procollagen Type I N-Terminal Propeptide (P1NP) | 2.33 percent change |
| MK-5442 10 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Procollagen Type I N-Terminal Propeptide (P1NP) | 21.30 percent change |
| MK-5442 15 mg | LS Mean Percent Change From Baseline to Month 6 in Serum Procollagen Type I N-Terminal Propeptide (P1NP) | 38.41 percent change |
| Placebo | LS Mean Percent Change From Baseline to Month 6 in Serum Procollagen Type I N-Terminal Propeptide (P1NP) | -18.36 percent change |
p-value: <0.00195% CI: [37.62, 76.35]Longitudinal Data Analysis
p-value: <0.00195% CI: [22.44, 57.17]Longitudinal Data Analysis
p-value: 0.00395% CI: [5.72, 35.78]Longitudinal Data Analysis
p-value: 0.26595% CI: [-4.81, 22.05]Longitudinal Data Analysis
p-value: 0.26595% CI: [-3.4, 20.21]Longitudinal Data Analysis
Secondary
LS Mean Percent Change From Baseline to Month 6 in the Ratio of Urinary N-Telopeptides of Type I Collagen to Creatinine (u-NTx/Cr)
The ratio of u-NTx to Cr is a biomarker for bone resorption. It is measured in the serum in units of nanomoles (nm) of bone collagen equivalents (BCE)/millimoles of creatinine (Cr).
Time frame: Baseline and Month 6
Population: Per Protocol population; defined as the subset of the APaT population that excluded participants based on critical protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-5442 2.5 mg | LS Mean Percent Change From Baseline to Month 6 in the Ratio of Urinary N-Telopeptides of Type I Collagen to Creatinine (u-NTx/Cr) | -12.18 percent change |
| MK-5442 5 mg | LS Mean Percent Change From Baseline to Month 6 in the Ratio of Urinary N-Telopeptides of Type I Collagen to Creatinine (u-NTx/Cr) | -9.46 percent change |
| MK-5442 7.5 mg | LS Mean Percent Change From Baseline to Month 6 in the Ratio of Urinary N-Telopeptides of Type I Collagen to Creatinine (u-NTx/Cr) | -20.73 percent change |
| MK-5442 10 mg | LS Mean Percent Change From Baseline to Month 6 in the Ratio of Urinary N-Telopeptides of Type I Collagen to Creatinine (u-NTx/Cr) | -7.82 percent change |
| MK-5442 15 mg | LS Mean Percent Change From Baseline to Month 6 in the Ratio of Urinary N-Telopeptides of Type I Collagen to Creatinine (u-NTx/Cr) | 1.87 percent change |
| Placebo | LS Mean Percent Change From Baseline to Month 6 in the Ratio of Urinary N-Telopeptides of Type I Collagen to Creatinine (u-NTx/Cr) | -17.90 percent change |
p-value: 0.0295% CI: [2.26, 37.46]Longitudinal Data Analysis Model
p-value: 0.35795% CI: [-6.16, 26.41]Longitudinal Data Analysis Model
p-value: 0.64295% CI: [-14.81, 9.14]Longitudinal Data Analysis Model
p-value: 0.43495% CI: [-7.09, 24.04]Longitudinal Data Analysis Model
p-value: 0.57995% CI: [-8.62, 20.1]Longitudinal Data Analysis Model
Secondary
LS Mean Percent Change From Baseline to Month 6 in Total Body aBMD
DXA was used to assess and measure aBMD of the total body. Areal BMD was measured as areal density using units of gram (gm) of tissue /centimeter of tissue squared (cm\^2).
Time frame: Baseline and Month 6
Population: Full Analysis Set (FAS); participants who received at least one dose of study treatment, had post-randomization data subsequent to at least one dose of study treatment, and who had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-5442 2.5 mg | LS Mean Percent Change From Baseline to Month 6 in Total Body aBMD | 0.43 percent change |
| MK-5442 5 mg | LS Mean Percent Change From Baseline to Month 6 in Total Body aBMD | 0.28 percent change |
| MK-5442 7.5 mg | LS Mean Percent Change From Baseline to Month 6 in Total Body aBMD | 0.80 percent change |
| MK-5442 10 mg | LS Mean Percent Change From Baseline to Month 6 in Total Body aBMD | 0.21 percent change |
| MK-5442 15 mg | LS Mean Percent Change From Baseline to Month 6 in Total Body aBMD | 0.09 percent change |
| Placebo | LS Mean Percent Change From Baseline to Month 6 in Total Body aBMD | 0.27 percent change |
p-value: 0.97695% CI: [-1.12, 0.77]Longitudinal Data Analysis Model
p-value: 0.98295% CI: [-0.93, 0.8]Longitudinal Data Analysis Model
p-value: 0.48995% CI: [-0.43, 1.49]Longitudinal Data Analysis Model
p-value: 0.98295% CI: [-0.75, 0.78]Longitudinal Data Analysis Model
p-value: 0.97695% CI: [-0.76, 1.08]Longitudinal Data Analysis Model
Secondary
LS Mean Percent Change From Baseline to Month 6 in Total Hip aBMD
DXA was used to assess and measure aBMD of the total hip. Areal BMD was measured as areal density using units of gram (gm) of tissue /centimeter of tissue squared (cm\^2).
Time frame: Baseline and Month 6
Population: Full Analysis Set (FAS); participants who received at least one dose of study treatment, had post-randomization data subsequent to at least one dose of study treatment, and who had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-5442 2.5 mg | LS Mean Percent Change From Baseline to Month 6 in Total Hip aBMD | -0.20 percent change |
| MK-5442 5 mg | LS Mean Percent Change From Baseline to Month 6 in Total Hip aBMD | -0.32 percent change |
| MK-5442 7.5 mg | LS Mean Percent Change From Baseline to Month 6 in Total Hip aBMD | 0.32 percent change |
| MK-5442 10 mg | LS Mean Percent Change From Baseline to Month 6 in Total Hip aBMD | 0.07 percent change |
| MK-5442 15 mg | LS Mean Percent Change From Baseline to Month 6 in Total Hip aBMD | 0.33 percent change |
| Placebo | LS Mean Percent Change From Baseline to Month 6 in Total Hip aBMD | 0.08 percent change |
p-value: 0.95995% CI: [-1.03, 1.51]Longitudinal Data Analysis Model
p-value: 0.97195% CI: [-1.08, 1.04]Longitudinal Data Analysis Model
p-value: 0.95995% CI: [-0.95, 1.42]Longitudinal Data Analysis Model
p-value: 0.91595% CI: [-1.78, 0.97]Longitudinal Data Analysis Model
p-value: 0.95995% CI: [-1.6, 1.04]Longitudinal Data Analysis Model
Secondary
LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Hip
Quantitative computed tomography (QCT) technology was used to assess and measure bone mineral content volumetrically (ie, in grams of tissue per centimeter of tissue cubed).
Time frame: Baseline and Month 6
Population: Full Analysis Set (FAS); participants who received at least one dose of study treatment, had post-randomization data subsequent to at least one dose of study treatment, and who had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-5442 2.5 mg | LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Hip | -0.41 percent change |
| MK-5442 5 mg | LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Hip | -0.34 percent change |
| MK-5442 7.5 mg | LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Hip | -0.89 percent change |
| MK-5442 10 mg | LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Hip | -0.88 percent change |
| MK-5442 15 mg | LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Hip | -0.80 percent change |
| Placebo | LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Hip | -0.37 percent change |
p-value: 0.90195% CI: [-2.03, 1.17]Longitudinal Data Analysis Model
p-value: 0.90195% CI: [-2.18, 1.17]Longitudinal Data Analysis Model
p-value: 0.90195% CI: [-2.17, 1.13]Longitudinal Data Analysis Model
p-value: 0.99795% CI: [-1.29, 1.35]Longitudinal Data Analysis Model
p-value: 0.99795% CI: [-1.51, 1.43]Longitudinal Data Analysis Model
Secondary
LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Lumbar Spine
Quantitative computed tomography (QCT) technology was used at baseline and periodically through out the study to assess and measure bone mineral content volumetrically (ie, in grams of tissue per centimeter of tissue cubed).
Time frame: Baseline and Month 6
Population: Full Analysis Set (FAS); participants who received at least one dose of study treatment, had post-randomization data subsequent to at least one dose of study treatment, and who had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-5442 2.5 mg | LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Lumbar Spine | 1.94 percent change |
| MK-5442 5 mg | LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Lumbar Spine | 0.94 percent change |
| MK-5442 7.5 mg | LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Lumbar Spine | 1.83 percent change |
| MK-5442 10 mg | LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Lumbar Spine | 3.35 percent change |
| MK-5442 15 mg | LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Lumbar Spine | 1.06 percent change |
| Placebo | LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Lumbar Spine | 1.43 percent change |
p-value: 0.97995% CI: [-2.73, 1.99]Longitudinal Data Analysis Model
p-value: 0.36395% CI: [-1.1, 4.95]Longitudinal Data Analysis Model
p-value: 0.97995% CI: [-2.18, 2.98]Longitudinal Data Analysis Model
p-value: 0.97995% CI: [-3.27, 2.3]Longitudinal Data Analysis Model
p-value: 0.97995% CI: [-2.34, 3.37]Longitudinal Data Analysis Model
Secondary
LS Mean Percent Change From Baseline to Month 6 in Trochanter aBMD
DXA was used to assess and measure aBMD of the trochanter. Areal BMD was measured as areal density using units of gram (gm) of tissue /centimeter of tissue squared (cm\^2).
Time frame: Baseline and Month 6
Population: Full Analysis Set (FAS); participants who received at least one dose of study treatment, had post-randomization data subsequent to at least one dose of study treatment, and who had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-5442 2.5 mg | LS Mean Percent Change From Baseline to Month 6 in Trochanter aBMD | 0.41 percent change |
| MK-5442 5 mg | LS Mean Percent Change From Baseline to Month 6 in Trochanter aBMD | 0.95 percent change |
| MK-5442 7.5 mg | LS Mean Percent Change From Baseline to Month 6 in Trochanter aBMD | 0.54 percent change |
| MK-5442 10 mg | LS Mean Percent Change From Baseline to Month 6 in Trochanter aBMD | 0.49 percent change |
| MK-5442 15 mg | LS Mean Percent Change From Baseline to Month 6 in Trochanter aBMD | 1.10 percent change |
| Placebo | LS Mean Percent Change From Baseline to Month 6 in Trochanter aBMD | 0.49 percent change |
p-value: 0.93395% CI: [-1.56, 2.77]Longitudinal Data Analysis Model
p-value: 0.99995% CI: [-1.69, 1.68]Longitudinal Data Analysis Model
p-value: 0.99995% CI: [-1.84, 1.93]Longitudinal Data Analysis Model
p-value: 0.95995% CI: [-1.67, 2.57]Longitudinal Data Analysis Model
p-value: 0.99995% CI: [-2.1, 1.94]Longitudinal Data Analysis Model