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.
Amendment 4 of the protocol changed the duration of the study from 2 years to 6 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
383
MK-5442 2.5 mg, 5 mg, 7.5 mg, 10 mg, or 15 mg tablet once daily for at least 6 months.
Dose-matched oral placebo to MK-5442
Vitamin D3, two 400 IU tablets daily throughout the study.
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
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
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
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
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
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Participants who had a calcium intake of less than 1200 mg/day at baseline received a daily 500 mg calcium supplement throughout the study.
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
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
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
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
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
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
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
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
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
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
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
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