Osteoporosis, Postmenopausal Osteoporosis
Conditions
Brief summary
This study seeks to demonstrate that additional gain in bone mineral density (BMD) can be achieved by switching to MK-5442 from an oral bisphosphonate in participants who have been receiving oral bisphosphonate therapy for at least 3 years.
Detailed description
The study was originally planned for a duration of 2 years and included efficacy analysis of a 15 mg MK-5442 treatment arm. Amendment 1 of the protocol eliminated the 2nd year of the study as well the 15-mg arm. Enrollment into the 15-mg MK-5442 arm was stopped as a result of the amendment and all participants who had been randomly assigned to the MK-5442 15-mg treatment arm were discontinued from the study.
Interventions
DRUGMK-5442
MK-5442 tablets (randomized to a dose of 5, 7.5, 10 or 15 mg) taken orally, once-daily, for 12 months
DRUGPlacebo to MK-5442
Matching placebo to MK-5442 taken orally, once-daily, for 12 months
Alendronate tablets 70 mg, taken orally, once-weekly, for 12 months
DRUGVitamin D3
Vitamin D3 (cholecalciferol) administered orally, at a dose of 5600 IU (two tablets, 2800 IU each), once-weekly for 12 months
DRUGCalcium carbonate
Participants who qualify (those who have a calcium intake of less than 1200 mg/day) will receive oral supplemental calcium carbonate, at a dose of either 400 mg or 500 mg, once-daily, for 12 months
Placebo to alendronate once-weekly for 12 months
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
* Taking oral bisphosphonate treatment for osteoporosis for at least 3 of the past 4 years. At present, and for the past 12 months, treated with alendronate * Bone Mineral Density (BMD) T-score that is ≤ -1.5 at one or more of the following anatomic sites; lumbar spine, femoral neck, trochanter, and total hip, AND a BMD T-score at all of these sites that is ≥ -4.0, AND a history of at least one fragility fracture, OR, a BMD T-score that is ≤ -2.5 at one or more of the following anatomic sites; lumbar spine, femoral neck, trochanter, and total hip, AND a BMD T-score at all of these sites that is ≥ -4.0 * Postmenopausal for at least 5 years
Exclusion criteria
* Obesity (ie, weight greater than 250 pounds) that prohibits the use of dual-emission X-ray absorptiometry (DXA) * Received intravenous (IV) bisphosphonates, fluoride treatment at a dose \>1 mg/day for more than 2 weeks, strontium, growth hormone, a cathepsin K (CTSK) inhibitor, or a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor at any time in the past * Use of oral bisphosphonates other than alendronate in the last 12 months, parathyroid hormone (PTH) in the last 24 months, cyclosporin for more than 2 weeks in the last 6 months, heparin in the last 2 weeks, or anabolic steroids or glucocorticoids for more than 2 weeks in the past 6 months * Use of estrogen with or without progestin or a selective estrogen receptor modulator (SERM) in the last 6 months or calcitonin in the last 30 days * Has used pioglitazone hydrochloride or rosiglitazone hydrochloride in the last 6 months * Taking more than 10,000 International Units (IU) vitamin A daily or more than 5,000 IU vitamin D daily * Has had a total thyroidectomy * History of Paget's disease * Has human immunodeficiency virus (HIV) * History of cancer in the last 5 years, except certain skin or cervical cancers * History of major upper gastrointestinal (GI) mucosal erosive disease * Unable to adhere to dosing instructions for alendronate in regard to fasting and positioning * Not ambulatory
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD) | Baseline and Month 12 | Areal bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) scanning technology. Scanning is performed with two X-ray beams with different energy levels which are aimed at the participant's bones. When soft tissue absorption is subtracted out, the BMD is determined from the absorption of each beam by bone. BMD = BMC / W, where BMD = bone mineral density in g/cm\^2, BMC = bone mineral content in g/cm, and W = width at the scanned line in cm |
| Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | Baseline through Month 12 | 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 at least a one calcium level value ≥10.6 mg/dL were considered as having a Tier 1 adverse event (AE). A Tier 1 AE was an AE of special interest identified a priori that could be used for inferential testing for statistical significance for between-group comparisons. |
| Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | Baseline through Month 12 | 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 at least one albumin-corrected calcium level value ≥10.6 mg/dL were considered as having a Tier 1 AE (an AE of special interest identified a priori that could be used for inferential testing for statistical significance for between-group comparisons). |
| Number of Participants With Predefined Tier 1 Adverse Events | Baseline through Month 12 | Osteonecrosis of the jaw (ONJ), kidney stones, and bone neoplasms were predefined Tier-1 AEs in the study (an AE of special interest identified a priori that could be used for inferential testing for statistical significance for between-group comparisons). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Percent Change From Baseline to Month 12 in 1/3 Distal Forearm Areal BMD | Baseline and Month 12 | Areal bone mineral density (BMD) was measured using DXA scanning technology. Scanning is performed with two X-ray beams with different energy levels which are aimed at the participant's bones. When soft tissue absorption is subtracted out, the BMD is determined from the absorption of each beam by bone. BMD = BMC / W, where BMD = bone mineral density in g/cm\^2, BMC = bone mineral content in g/cm, and W = width at the scanned line in cm |
| Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD (vBMD) of the Lumbar Spine | Baseline and Month 12 | vBMD was measured using quantitative computed tomography (QCT) in order to assess bone strength. Quantitative computed tomography is a three-dimensional non-projectional technique that quantifies trabecular and cortical BMD in the lumbar spine and hip as a true volumetric mineral density in g/cm\^3. |
| Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD of the Hip | Baseline and Month 12 | vBMD was measured using QCT in order to assess bone strength. QCT is a three-dimensional non-projectional technique that quantifies trabecular and cortical BMD in the lumbar spine and hip as a true volumetric mineral density in g/cm\^3. |
| Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Lumbar Spine | Baseline and Month 12 | vBMD was measured using QCT in order to assess bone strength. QCT is a three-dimensional non-projectional technique that quantifies trabecular and cortical BMD in the lumbar spine and hip as a true volumetric mineral density in g/cm\^3. |
| Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Hip | Baseline and Month 12 | vBMD was measured using QCT in order to assess bone strength. QCT is a three-dimensional non-projectional technique that quantifies trabecular and cortical BMD in the lumbar spine and hip as a true volumetric mineral density in g/cm\^3. |
| Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD | Baseline and Month 12 | Areal bone mineral density (BMD) was measured using DXA scanning technology. Scanning is performed with two X-ray beams with different energy levels which are aimed at the participant's bones. When soft tissue absorption is subtracted out, the BMD is determined from the absorption of each beam by bone. BMD = BMC / W, where BMD = bone mineral density in g/cm\^2, BMC = bone mineral content in g/cm, and W = width at the scanned line in cm |
| Least Squares Mean Percent Change From Baseline to Month 12 in Serum C-Terminal Propeptide of Type 1 Collagen (s-CTx) | Baseline and Month 12 | C-Terminal Telopeptide Collagen I is used as a serum-marker of bone resorption in the assessment of osteoporosis and in measured in units of nanograms (n)/milliliter (ml). |
| Least Squares Mean Percent Change From Baseline to Month 12 in Serum N-Terminal Propeptide (s-P1NP) | Baseline and Month 12 | s-P1NP is a sensitive marker of bone formation rate in the assessment of osteoporosis and is measured in units of ng/ml. |
| Least Squares Mean Percent Change From Baseline to Month 12 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) | Baseline and Month 12 | Bone Specific Alkaline Phosphatase is a biomarker of bone formation and is measured in units of μg/L. |
| Least Squares Mean Percent Change From Baseline to Month 12 in Serum Osteocalcin | Baseline and Month 12 | Serum osteocalcin is a biomarker of bone formation and is measured using units of nanograms (ng) / milliliter (mL). |
| Least Squares Mean Percent Change From Baseline to Month 12 in Urinary-N Telopeptides of Type 1 Collagen (u-NTx) | Baseline and Month 12 | Urinary, type I collagen, crosslinked N-telopeptide (uNTx) is a biomarker used to measure the rate of bone turnover found in urine. uNTx was expressed in units of nanomoles (nM) per bone collagen equivalents (BCE) per millimoles of creatinine (Cr) or nM/BCE/mM Cr |
| Least Squares Mean Percent Change From Baseline to Month 12 in Femoral Neck Areal BMD | Baseline and Month 12 | Areal bone mineral density (BMD) was measured using DXA scanning technology. Scanning is performed with two X-ray beams with different energy levels which are aimed at the participant's bones. When soft tissue absorption is subtracted out, the BMD is determined from the absorption of each beam by bone. BMD = BMC / W, where BMD = bone mineral density in g/cm\^2, BMC = bone mineral content in g/cm, and W = width at the scanned line in cm |
| Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD | Baseline and Month 12 | Areal bone mineral density (BMD) was measured using DXA scanning technology. Scanning is performed with two X-ray beams with different energy levels which are aimed at the participant's bones. When soft tissue absorption is subtracted out, the BMD is determined from the absorption of each beam by bone. BMD = BMC / W, where BMD = bone mineral density in g/cm\^2, BMC = bone mineral content in g/cm, and W = width at the scanned line in cm |
| Least Squares Mean Percent Change From Baseline to Month 12 in Total Body Areal BMD | Baseline and Month 12 | Areal bone mineral density (BMD) was measured using DXA scanning technology. Scanning is performed with two X-ray beams with different energy levels which are aimed at the participant's bones. When soft tissue absorption is subtracted out, the BMD is determined from the absorption of each beam by bone. BMD = BMC / W, where BMD = bone mineral density in g/cm\^2, BMC = bone mineral content in g/cm, and W = width at the scanned line in cm |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received either matching placebo to alendronate (administered orally, once-weekly) or matching placebo to MK-5442 (administered orally, once-daily) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment. | 88 |
| MK-5442 5 mg Participants received 5 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment. | 88 |
| MK-5442 7.5 mg Participants received 7.5 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment. | 88 |
| MK-5442 10 mg Participants received 10 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment. | 87 |
| MK-5442 15 mg Participants received 15 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment. | 88 |
| Alendronate 70 mg Participants received 70 mg alendronate (orally, once-weekly) plus matching placebo to MK-5442 (administered orally, once-daily) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment. | 87 |
| Total | 526 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 4 | 12 | 17 | 31 | 3 |
| Overall Study | Lack of Efficacy | 3 | 0 | 1 | 3 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 3 | 3 | 2 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Progressive Disease | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 3 | 4 | 1 | 2 | 3 | 4 |
| Overall Study | Study Terminated by Sponsor | 0 | 1 | 0 | 0 | 46 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 6 | 9 | 5 | 5 | 9 |
Baseline characteristics
| Characteristic | Placebo | MK-5442 5 mg | MK-5442 7.5 mg | MK-5442 10 mg | MK-5442 15 mg | Alendronate 70 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 67.8 Years STANDARD_DEVIATION 7.8 | 66.5 Years STANDARD_DEVIATION 8.8 | 67.3 Years STANDARD_DEVIATION 7.1 | 68.2 Years STANDARD_DEVIATION 6.9 | 68.1 Years STANDARD_DEVIATION 7.4 | 66.9 Years STANDARD_DEVIATION 7.5 | 67.5 Years STANDARD_DEVIATION 7.6 |
| Sex: Female, Male Female | 88 Participants | 88 Participants | 88 Participants | 87 Participants | 88 Participants | 87 Participants | 526 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 / 88 | 18 / 87 | 26 / 88 | 32 / 87 | 28 / 88 | 10 / 84 |
| serious Total, serious adverse events | 6 / 88 | 5 / 87 | 4 / 88 | 6 / 87 | 4 / 88 | 1 / 88 |
Outcome results
Primary
Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD)
Areal bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) scanning technology. Scanning is performed with two X-ray beams with different energy levels which are aimed at the participant's bones. When soft tissue absorption is subtracted out, the BMD is determined from the absorption of each beam by bone. BMD = BMC / W, where BMD = bone mineral density in g/cm\^2, BMC = bone mineral content in g/cm, and W = width at the scanned line in cm
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS): participants who received at least one dose of study treatment, had at least one post-randomization observation, and who had baseline data.~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD) | -0.36 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD) | -0.67 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD) | -0.52 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD) | -0.53 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD) | 1.29 percent change |
p-value: 0.01295% CI: [-3.58, -0.35]Longitudinal Data Analysis Model
p-value: 0.01995% CI: [-3.37, -0.25]Longitudinal Data Analysis Model
p-value: 0.01995% CI: [-3.23, -0.41]Longitudinal Data Analysis Model
Primary
Number of Participants With Predefined Tier 1 Adverse Events
Osteonecrosis of the jaw (ONJ), kidney stones, and bone neoplasms were predefined Tier-1 AEs in the study (an AE of special interest identified a priori that could be used for inferential testing for statistical significance for between-group comparisons).
Time frame: Baseline through Month 12
Population: All Participants as Treated (APaT): all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Predefined Tier 1 Adverse Events | Bone neoplasms | 0 Participants |
| Placebo | Number of Participants With Predefined Tier 1 Adverse Events | Kidney stones | 3 Participants |
| Placebo | Number of Participants With Predefined Tier 1 Adverse Events | Osteonecrosis of the jaw | 0 Participants |
| MK-5442 5 mg | Number of Participants With Predefined Tier 1 Adverse Events | Osteonecrosis of the jaw | 0 Participants |
| MK-5442 5 mg | Number of Participants With Predefined Tier 1 Adverse Events | Kidney stones | 0 Participants |
| MK-5442 5 mg | Number of Participants With Predefined Tier 1 Adverse Events | Bone neoplasms | 0 Participants |
| MK-5442 7.5mg | Number of Participants With Predefined Tier 1 Adverse Events | Bone neoplasms | 0 Participants |
| MK-5442 7.5mg | Number of Participants With Predefined Tier 1 Adverse Events | Osteonecrosis of the jaw | 0 Participants |
| MK-5442 7.5mg | Number of Participants With Predefined Tier 1 Adverse Events | Kidney stones | 0 Participants |
| MK-5442 10 mg | Number of Participants With Predefined Tier 1 Adverse Events | Kidney stones | 0 Participants |
| MK-5442 10 mg | Number of Participants With Predefined Tier 1 Adverse Events | Osteonecrosis of the jaw | 0 Participants |
| MK-5442 10 mg | Number of Participants With Predefined Tier 1 Adverse Events | Bone neoplasms | 0 Participants |
| Alendronate 70 mg | Number of Participants With Predefined Tier 1 Adverse Events | Osteonecrosis of the jaw | 0 Participants |
| Alendronate 70 mg | Number of Participants With Predefined Tier 1 Adverse Events | Kidney stones | 0 Participants |
| Alendronate 70 mg | Number of Participants With Predefined Tier 1 Adverse Events | Bone neoplasms | 0 Participants |
| Alendronate 70 mg | Number of Participants With Predefined Tier 1 Adverse Events | Osteonecrosis of the jaw | 0 Participants |
| Alendronate 70 mg | Number of Participants With Predefined Tier 1 Adverse Events | Bone neoplasms | 0 Participants |
| Alendronate 70 mg | Number of Participants With Predefined Tier 1 Adverse Events | Kidney stones | 1 Participants |
Primary
Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once
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 at least one albumin-corrected calcium level value ≥10.6 mg/dL were considered as having a Tier 1 AE (an AE of special interest identified a priori that could be used for inferential testing for statistical significance for between-group comparisons).
Time frame: Baseline through Month 12
Population: All Participants as Treated (APaT): all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥11.1 ng/mL | 1 Participants |
| Placebo | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥10.6 ng/mL | 1 Participants |
| Placebo | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥12.1 ng/mL | 0 Participants |
| MK-5442 5 mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥11.1 ng/mL | 0 Participants |
| MK-5442 5 mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥10.6 ng/mL | 3 Participants |
| MK-5442 5 mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥12.1 ng/mL | 0 Participants |
| MK-5442 7.5mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥11.1 ng/mL | 1 Participants |
| MK-5442 7.5mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥10.6 ng/mL | 7 Participants |
| MK-5442 7.5mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥12.1 ng/mL | 0 Participants |
| MK-5442 10 mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥11.1 ng/mL | 3 Participants |
| MK-5442 10 mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥10.6 ng/mL | 13 Participants |
| MK-5442 10 mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥12.1 ng/mL | 1 Participants |
| Alendronate 70 mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥11.1 ng/mL | 9 Participants |
| Alendronate 70 mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥10.6 ng/mL | 28 Participants |
| Alendronate 70 mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥12.1 ng/mL | 0 Participants |
| Alendronate 70 mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥10.6 ng/mL | 2 Participants |
| Alendronate 70 mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥12.1 ng/mL | 0 Participants |
| Alendronate 70 mg | Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once | ≥11.1 ng/mL | 0 Participants |
Primary
Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once
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 at least a one calcium level value ≥10.6 mg/dL were considered as having a Tier 1 adverse event (AE). A Tier 1 AE was an AE of special interest identified a priori that could be used for inferential testing for statistical significance for between-group comparisons.
Time frame: Baseline through Month 12
Population: All Participants as Treated (APaT): all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥11.1 ng/mL | 1 Participants |
| Placebo | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥10.6 ng/mL | 3 Participants |
| Placebo | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥12.1 ng/mL | 0 Participants |
| MK-5442 5 mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥11.1 ng/mL | 1 Participants |
| MK-5442 5 mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥10.6 ng/mL | 16 Participants |
| MK-5442 5 mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥12.1 ng/mL | 0 Participants |
| MK-5442 7.5mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥11.1 ng/mL | 4 Participants |
| MK-5442 7.5mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥10.6 ng/mL | 19 Participants |
| MK-5442 7.5mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥12.1 ng/mL | 0 Participants |
| MK-5442 10 mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥11.1 ng/mL | 7 Participants |
| MK-5442 10 mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥10.6 ng/mL | 27 Participants |
| MK-5442 10 mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥12.1 ng/mL | 1 Participants |
| Alendronate 70 mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥11.1 ng/mL | 19 Participants |
| Alendronate 70 mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥10.6 ng/mL | 39 Participants |
| Alendronate 70 mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥12.1 ng/mL | 1 Participants |
| Alendronate 70 mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥10.6 ng/mL | 7 Participants |
| Alendronate 70 mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥12.1 ng/mL | 0 Participants |
| Alendronate 70 mg | Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once | ≥11.1 ng/mL | 1 Participants |
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 in 1/3 Distal Forearm Areal BMD
Areal bone mineral density (BMD) was measured using DXA scanning technology. Scanning is performed with two X-ray beams with different energy levels which are aimed at the participant's bones. When soft tissue absorption is subtracted out, the BMD is determined from the absorption of each beam by bone. BMD = BMC / W, where BMD = bone mineral density in g/cm\^2, BMC = bone mineral content in g/cm, and W = width at the scanned line in cm
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS): participants who received at least one dose of study treatment, had at least one post-randomization observation, and who had baseline data.~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline to Month 12 in 1/3 Distal Forearm Areal BMD | -0.54 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline to Month 12 in 1/3 Distal Forearm Areal BMD | -1.38 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline to Month 12 in 1/3 Distal Forearm Areal BMD | -0.92 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline to Month 12 in 1/3 Distal Forearm Areal BMD | -2.01 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline to Month 12 in 1/3 Distal Forearm Areal BMD | -0.91 percent change |
p-value: 0.6895% CI: [-1.88, 0.94]Longitudinal Data Analysis Model
p-value: 0.99395% CI: [-1.3, 1.28]Longitudinal Data Analysis Model
p-value: 0.2395% CI: [-2.67, 0.46]Longitudinal Data Analysis Model
p-value: 0.33395% CI: [-2.29, 0.61]Longitudinal Data Analysis Model
p-value: 0.57795% CI: [-1.69, 0.94]Longitudinal Data Analysis Model
p-value: 0.07895% CI: [-3.07, 0.12]Longitudinal Data Analysis Model
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Hip
vBMD was measured using QCT in order to assess bone strength. QCT is a three-dimensional non-projectional technique that quantifies trabecular and cortical BMD in the lumbar spine and hip as a true volumetric mineral density in g/cm\^3.
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS), QCT Subset: QCT was performed on a subset of the FAS (participants who received at least one dose of study treatment, had at least one post-randomization observation, and who had baseline data).~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcomes analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Hip | 0.10 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Hip | -0.49 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Hip | -0.15 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Hip | -0.16 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Hip | 0.99 percent change |
p-value: 0.0195% CI: [-2.66, -0.29]Longitudinal Data Analysis Model
p-value: 0.05395% CI: [-2.29, 0.01]Longitudinal Data Analysis Model
p-value: 0.05395% CI: [-2.19, -0.11]Longitudinal Data Analysis Model
p-value: 0.50995% CI: [-1.77, 0.6]Longitudinal Data Analysis Model
p-value: 0.84395% CI: [-1.27, 0.77]Longitudinal Data Analysis Model
p-value: 0.84395% CI: [-1.43, 0.92]Longitudinal Data Analysis Model
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Lumbar Spine
vBMD was measured using QCT in order to assess bone strength. QCT is a three-dimensional non-projectional technique that quantifies trabecular and cortical BMD in the lumbar spine and hip as a true volumetric mineral density in g/cm\^3.
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS), QCT Subset: QCT was performed on a subset of the FAS (participants who received at least one dose of study treatment, had at least one post-randomization observation, and who had baseline data).~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Lumbar Spine | -0.67 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Lumbar Spine | -3.41 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Lumbar Spine | 14.66 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Lumbar Spine | -0.34 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Lumbar Spine | 12.80 percent change |
p-value: 0.22795% CI: [-39.15, 6.72]Longitudinal Data Analysis Model
p-value: 0.85395% CI: [-17.9, 21.61]Longitudinal Data Analysis Model
p-value: 0.32795% CI: [-35.67, 9.39]Longitudinal Data Analysis Model
p-value: 0.9495% CI: [-23.91, 18.43]Longitudinal Data Analysis Model
p-value: 0.27395% CI: [-7.86, 38.52]Longitudinal Data Analysis Model
p-value: 0.97395% CI: [-19.23, 19.9]Longitudinal Data Analysis Model
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 in Femoral Neck Areal BMD
Areal bone mineral density (BMD) was measured using DXA scanning technology. Scanning is performed with two X-ray beams with different energy levels which are aimed at the participant's bones. When soft tissue absorption is subtracted out, the BMD is determined from the absorption of each beam by bone. BMD = BMC / W, where BMD = bone mineral density in g/cm\^2, BMC = bone mineral content in g/cm, and W = width at the scanned line in cm
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS): participants who received at least one dose of study treatment, had at least one post-randomization observation, and who had baseline data.~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline to Month 12 in Femoral Neck Areal BMD | -1.26 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Femoral Neck Areal BMD | -2.12 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline to Month 12 in Femoral Neck Areal BMD | -1.37 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Femoral Neck Areal BMD | -1.84 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Femoral Neck Areal BMD | -0.08 percent change |
p-value: 0.00295% CI: [-3.43, -0.64]Longitudinal Data Analysis Model
p-value: 0.03595% CI: [-2.48, -0.09]Longitudinal Data Analysis Model
p-value: 0.00995% CI: [-3.14, -0.38]Longitudinal Data Analysis Model
p-value: 0.33595% CI: [-2.26, 0.54]Longitudinal Data Analysis Model
p-value: 0.85795% CI: [-1.3, 1.08]Longitudinal Data Analysis Model
p-value: 0.54295% CI: [-1.96, 0.79]Longitudinal Data Analysis Model
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP)
Bone Specific Alkaline Phosphatase is a biomarker of bone formation and is measured in units of μg/L.
Time frame: Baseline and Month 12
Population: Per Protocol Population: defined as the subset of the APaT population that excluded participants based on critical protocol violations.~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline to Month 12 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) | 29.51 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) | 50.04 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline to Month 12 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) | 49.98 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) | 51.64 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) | -3.83 percent change |
p-value: <0.00195% CI: [39.31, 68.6]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [41.37, 66.38]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [41.19, 69.94]Constrained Longitudinal Data Analysis
p-value: 0.00995% CI: [5.96, 35.03]Constrained Longitudinal Data Analysis
p-value: 0.00995% CI: [5.96, 35.03]Constrained Longitudinal Data Analysis
p-value: 0.00995% CI: [4.47, 39.89]Constrained Longitudinal Data Analysis
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 in Serum C-Terminal Propeptide of Type 1 Collagen (s-CTx)
C-Terminal Telopeptide Collagen I is used as a serum-marker of bone resorption in the assessment of osteoporosis and in measured in units of nanograms (n)/milliliter (ml).
Time frame: Baseline and Month 12
Population: Per Protocol Population: defined as the subset of the APaT population that excluded participants based on critical protocol violations.~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline to Month 12 in Serum C-Terminal Propeptide of Type 1 Collagen (s-CTx) | 165.80 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Serum C-Terminal Propeptide of Type 1 Collagen (s-CTx) | 214.09 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline to Month 12 in Serum C-Terminal Propeptide of Type 1 Collagen (s-CTx) | 227.07 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Serum C-Terminal Propeptide of Type 1 Collagen (s-CTx) | 251.08 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Serum C-Terminal Propeptide of Type 1 Collagen (s-CTx) | 26.78 percent change |
p-value: <0.00195% CI: [154.44, 221.25]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [161.21, 240.91]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [180.19, 270.39]Constrained Longitudinal Data Analysis
p-value: 0.03495% CI: [3.75, 93.11]Constrained Longitudinal Data Analysis
p-value: 0.01995% CI: [8.8, 114.22]Constrained Longitudinal Data Analysis
p-value: 0.00295% CI: [26.7, 144.63]Constrained Longitudinal Data Analysis
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 in Serum N-Terminal Propeptide (s-P1NP)
s-P1NP is a sensitive marker of bone formation rate in the assessment of osteoporosis and is measured in units of ng/ml.
Time frame: Baseline and Month 12
Population: Per Protocol Population: defined as the subset of the APaT population that excluded participants based on critical protocol violations.~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline to Month 12 in Serum N-Terminal Propeptide (s-P1NP) | 68.61 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Serum N-Terminal Propeptide (s-P1NP) | 127.18 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline to Month 12 in Serum N-Terminal Propeptide (s-P1NP) | 125.69 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Serum N-Terminal Propeptide (s-P1NP) | 163.96 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Serum N-Terminal Propeptide (s-P1NP) | -5.85 percent change |
p-value: <0.00195% CI: [110.01, 156.75]Constrained Longitudinal Data Analysis
p-value: 0.00195% CI: [110.01, 156.75]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [110.7, 152.94]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [141.59, 199.11]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [29.42, 88.04]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [30.76, 83.64]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [60.4, 130.91]Constrained Longitudinal Data Analysis
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 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 12
Population: Analysis of osteocalcin was not conducted when it was determined that the efficacy of MK-5442 was not significantly different than placebo.
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 in Total Body Areal BMD
Areal bone mineral density (BMD) was measured using DXA scanning technology. Scanning is performed with two X-ray beams with different energy levels which are aimed at the participant's bones. When soft tissue absorption is subtracted out, the BMD is determined from the absorption of each beam by bone. BMD = BMC / W, where BMD = bone mineral density in g/cm\^2, BMC = bone mineral content in g/cm, and W = width at the scanned line in cm
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS): participants who received at least one dose of study treatment, had at least one post-randomization observation, and who had baseline data.~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline to Month 12 in Total Body Areal BMD | -0.17 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Total Body Areal BMD | -0.54 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline to Month 12 in Total Body Areal BMD | -0.69 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Total Body Areal BMD | -1.10 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Total Body Areal BMD | 0.82 percent change |
p-value: 0.00195% CI: [-2.18, -0.54]Longitudinal Data Analysis Model
p-value: 0.00195% CI: [-2.46, -0.55]Longitudinal Data Analysis Model
p-value: <0.00195% CI: [-2.93, -0.91]Longitudinal Data Analysis Model
p-value: 0.38395% CI: [-1.21, 0.46]Longitudinal Data Analysis Model
p-value: 0.38395% CI: [-1.49, 0.45]Longitudinal Data Analysis Model
p-value: 0.08495% CI: [-1.96, 0.09]Longitudinal Data Analysis Model
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD
Areal bone mineral density (BMD) was measured using DXA scanning technology. Scanning is performed with two X-ray beams with different energy levels which are aimed at the participant's bones. When soft tissue absorption is subtracted out, the BMD is determined from the absorption of each beam by bone. BMD = BMC / W, where BMD = bone mineral density in g/cm\^2, BMC = bone mineral content in g/cm, and W = width at the scanned line in cm
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS): participants who received at least one dose of study treatment, had at least one post-randomization observation, and who had baseline data.~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD | -1.44 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD | -2.18 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD | -2.16 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD | -1.66 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD | 0.46 percent change |
p-value: <0.00195% CI: [-3.22, -1.02]Longitudinal Data Analysis Model
p-value: <0.00195% CI: [-3.9, -1.38]Longitudinal Data Analysis Model
p-value: <0.00195% CI: [-3.83, -1.4]Longitudinal Data Analysis Model
p-value: 0.37695% CI: [-1.99, 0.52]Longitudinal Data Analysis Model
p-value: 0.37695% CI: [-1.93, 0.5]Longitudinal Data Analysis Model
p-value: 0.69995% CI: [-1.32, 0.88]Longitudinal Data Analysis Model
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD of the Hip
vBMD was measured using QCT in order to assess bone strength. QCT is a three-dimensional non-projectional technique that quantifies trabecular and cortical BMD in the lumbar spine and hip as a true volumetric mineral density in g/cm\^3.
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS), QCT Subset: QCT was performed on a subset of the FAS (participants who received at least one dose of study treatment, had at least one post-randomization observation, and who had baseline data).~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD of the Hip | -0.02 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD of the Hip | 0.76 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD of the Hip | 0.81 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD of the Hip | 0.27 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD of the Hip | 1.23 percent change |
p-value: 0.82495% CI: [-2.5, 1.56]Longitudinal Data Analysis Model
p-value: 0.82495% CI: [-2.28, 1.43]Longitudinal Data Analysis Model
p-value: 0.62495% CI: [-3.23, 1.31]Longitudinal Data Analysis Model
p-value: 0.795% CI: [-1.25, 2.82]Longitudinal Data Analysis Model
p-value: 0.795% CI: [-1.39, 3.06]Longitudinal Data Analysis Model
p-value: 0.75995% CI: [-1.6, 2.19]Longitudinal Data Analysis Model
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD (vBMD) of the Lumbar Spine
vBMD was measured using quantitative computed tomography (QCT) in order to assess bone strength. Quantitative computed tomography is a three-dimensional non-projectional technique that quantifies trabecular and cortical BMD in the lumbar spine and hip as a true volumetric mineral density in g/cm\^3.
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS), QCT Subset: QCT was performed on a subset of the FAS (participants who received at least one dose of study treatment, had at least one post-randomization observation, and who had baseline data).~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD (vBMD) of the Lumbar Spine | 0.18 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD (vBMD) of the Lumbar Spine | -0.25 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD (vBMD) of the Lumbar Spine | 0.08 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD (vBMD) of the Lumbar Spine | 0.16 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD (vBMD) of the Lumbar Spine | 1.74 percent change |
p-value: 0.09495% CI: [-4.22, 0.25]Longitudinal Data Analysis Model
p-value: 0.15795% CI: [-3.82, 0.5]Longitudinal Data Analysis Model
p-value: 0.15795% CI: [-3.53, 0.38]Longitudinal Data Analysis Model
p-value: 0.93795% CI: [-2.61, 1.76]Longitudinal Data Analysis Model
p-value: 0.99295% CI: [-2.21, 2.01]Longitudinal Data Analysis Model
p-value: 0.99295% CI: [-1.93, 1.9]Longitudinal Data Analysis Model
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD
Areal bone mineral density (BMD) was measured using DXA scanning technology. Scanning is performed with two X-ray beams with different energy levels which are aimed at the participant's bones. When soft tissue absorption is subtracted out, the BMD is determined from the absorption of each beam by bone. BMD = BMC / W, where BMD = bone mineral density in g/cm\^2, BMC = bone mineral content in g/cm, and W = width at the scanned line in cm
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS): participants who received at least one dose of study treatment, had at least one post-randomization observation, and who had baseline data.~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD | -0.30 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD | -1.56 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD | -1.50 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD | -1.52 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD | 1.68 percent change |
p-value: <0.00195% CI: [-4.91, -1.57]Longitudinal Data Analysis Model
p-value: <0.00195% CI: [-4.78, -1.57]Longitudinal Data Analysis Model
p-value: <0.00195% CI: [-4.66, -1.74]Longitudinal Data Analysis Model
p-value: 0.1895% CI: [-2.93, 0.4]Longitudinal Data Analysis Model
p-value: 0.1895% CI: [-2.81, 0.4]Longitudinal Data Analysis Model
p-value: 0.1895% CI: [-2.68, 0.23]Longitudinal Data Analysis Model
Secondary
Least Squares Mean Percent Change From Baseline to Month 12 in Urinary-N Telopeptides of Type 1 Collagen (u-NTx)
Urinary, type I collagen, crosslinked N-telopeptide (uNTx) is a biomarker used to measure the rate of bone turnover found in urine. uNTx was expressed in units of nanomoles (nM) per bone collagen equivalents (BCE) per millimoles of creatinine (Cr) or nM/BCE/mM Cr
Time frame: Baseline and Month 12
Population: Per Protocol Population: defined as the subset of the APaT population that excluded participants based on critical protocol violations.~The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Least Squares Mean Percent Change From Baseline to Month 12 in Urinary-N Telopeptides of Type 1 Collagen (u-NTx) | 63.64 percent change |
| MK-5442 5 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Urinary-N Telopeptides of Type 1 Collagen (u-NTx) | 86.51 percent change |
| MK-5442 7.5mg | Least Squares Mean Percent Change From Baseline to Month 12 in Urinary-N Telopeptides of Type 1 Collagen (u-NTx) | 83.32 percent change |
| MK-5442 10 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Urinary-N Telopeptides of Type 1 Collagen (u-NTx) | 107.44 percent change |
| Alendronate 70 mg | Least Squares Mean Percent Change From Baseline to Month 12 in Urinary-N Telopeptides of Type 1 Collagen (u-NTx) | 0.18 percent change |
p-value: <0.00195% CI: [64.87, 108.29]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [63, 101.66]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [82.03, 133.23]Constrained Longitudinal Data Analysis
p-value: 0.10495% CI: [-3.8, 49.68]Constrained Longitudinal Data Analysis
p-value: 0.12395% CI: [-5.11, 42.56]Constrained Longitudinal Data Analysis
p-value: 0.00395% CI: [12.85, 75.06]Constrained Longitudinal Data Analysis