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MK-5442

Phase 2

Osteoporosis | Small molecule | Endocrine |Merck & Company, Inc.|Last Updated: Jan 22, 2016

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment526
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00996801MK-5442 in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With an Oral Bisphosphonate (MK-5442-012)PHASE2 COMPLETED 526Nov 1, 2009Jun 1, 2011Jan 22, 2016 -
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Study Endpoints
Primary Endpoints
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 Endpoints
Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD
Baseline and Month 12
Least Squares Mean Percent Change From Baseline to Month 12 in Femoral Neck Areal BMD
Baseline and Month 12
Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD
Baseline and Month 12
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
PlaceboPLACEBO_COMPARATORParticipants 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.
MK-5442 5 mgEXPERIMENTALParticipants 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.
MK-5442 7.5 mgEXPERIMENTALParticipants 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.
MK-5442 10 mgEXPERIMENTALParticipants 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.
MK-5442 15 mgEXPERIMENTALParticipants 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.
Alendronate 70 mgACTIVE_COMPARATORParticipants 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.
Interventions
NameTypeDescription
MK-5442DRUGMK-5442 tablets (randomized to a dose of 5, 7.5, 10 or 15 mg) taken orally, once-daily, for 12 months
Placebo to MK-5442DRUGMatching placebo to MK-5442 taken orally, once-daily, for 12 months
Alendronate SodiumDRUGAlendronate tablets 70 mg, taken orally, once-weekly, for 12 months
Vitamin D3DRUGVitamin D3 (cholecalciferol) administered orally, at a dose of 5600 IU (two tablets, 2800 IU each), once-weekly for 12 months
Calcium carbonateDRUGParticipants 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 AlendronateDRUGPlacebo to alendronate once-weekly for 12 months
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Eligibility Criteria
Age Range45 Years — 85 Years
SexFEMALE
Healthy VolunteersNo

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 ...

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