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MK-5442 in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With an Oral Bisphosphonate (MK-5442-012)

Primary Purpose

Osteoporosis, Postmenopausal Osteoporosis

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
MK-5442
Placebo to MK-5442
Alendronate Sodium
Vitamin D3
Calcium carbonate
Placebo to Alendronate
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoporosis

Eligibility Criteria

45 Years - 85 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm Type

    Placebo Comparator

    Experimental

    Experimental

    Experimental

    Experimental

    Active Comparator

    Arm Label

    Placebo

    MK-5442 5 mg

    MK-5442 7.5 mg

    MK-5442 10 mg

    MK-5442 15 mg

    Alendronate 70 mg

    Arm Description

    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.

    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.

    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.

    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.

    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.

    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.

    Outcomes

    Primary Outcome Measures

    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
    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.
    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).
    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).

    Secondary Outcome Measures

    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
    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
    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
    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
    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
    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.
    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.
    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.
    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.
    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
    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).
    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.
    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.
    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).

    Full Information

    First Posted
    October 15, 2009
    Last Updated
    January 21, 2016
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00996801
    Brief Title
    MK-5442 in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With an Oral Bisphosphonate (MK-5442-012)
    Official Title
    A Phase IIb, Randomized, Double-Blind, Placebo- and Active-Controlled, Dose-Range-Finding Study to Evaluate the Effects of MK-5442 on Bone Mineral Density (BMD) in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With an Oral Bisphosphonate
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2016
    Overall Recruitment Status
    Completed
    Study Start Date
    November 2009 (undefined)
    Primary Completion Date
    June 2011 (Actual)
    Study Completion Date
    June 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Osteoporosis, Postmenopausal Osteoporosis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    526 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    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.
    Arm Title
    MK-5442 5 mg
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    MK-5442 7.5 mg
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    MK-5442 10 mg
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    MK-5442 15 mg
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Alendronate 70 mg
    Arm Type
    Active Comparator
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    MK-5442
    Intervention Description
    MK-5442 tablets (randomized to a dose of 5, 7.5, 10 or 15 mg) taken orally, once-daily, for 12 months
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to MK-5442
    Intervention Description
    Matching placebo to MK-5442 taken orally, once-daily, for 12 months
    Intervention Type
    Drug
    Intervention Name(s)
    Alendronate Sodium
    Other Intervention Name(s)
    FOSAMAX®
    Intervention Description
    Alendronate tablets 70 mg, taken orally, once-weekly, for 12 months
    Intervention Type
    Drug
    Intervention Name(s)
    Vitamin D3
    Other Intervention Name(s)
    Cholecalciferol
    Intervention Description
    Vitamin D3 (cholecalciferol) administered orally, at a dose of 5600 IU (two tablets, 2800 IU each), once-weekly for 12 months
    Intervention Type
    Drug
    Intervention Name(s)
    Calcium carbonate
    Intervention Description
    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
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to Alendronate
    Intervention Description
    Placebo to alendronate once-weekly for 12 months
    Primary Outcome Measure Information:
    Title
    Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD)
    Description
    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
    Title
    Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once
    Description
    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
    Title
    Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once
    Description
    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
    Title
    Number of Participants With Predefined Tier 1 Adverse Events
    Description
    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
    Secondary Outcome Measure Information:
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD
    Description
    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
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in Femoral Neck Areal BMD
    Description
    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
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD
    Description
    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
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in Total Body Areal BMD
    Description
    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
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in 1/3 Distal Forearm Areal BMD
    Description
    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
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD (vBMD) of the Lumbar Spine
    Description
    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
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD of the Hip
    Description
    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
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Lumbar Spine
    Description
    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
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Hip
    Description
    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
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in Urinary-N Telopeptides of Type 1 Collagen (u-NTx)
    Description
    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
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in Serum C-Terminal Propeptide of Type 1 Collagen (s-CTx)
    Description
    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
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in Serum N-Terminal Propeptide (s-P1NP)
    Description
    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
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP)
    Description
    Bone Specific Alkaline Phosphatase is a biomarker of bone formation and is measured in units of μg/L.
    Time Frame
    Baseline and Month 12
    Title
    Least Squares Mean Percent Change From Baseline to Month 12 in Serum Osteocalcin
    Description
    Serum osteocalcin is a biomarker of bone formation and is measured using units of nanograms (ng) / milliliter (mL).
    Time Frame
    Baseline and Month 12

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    45 Years
    Maximum Age & Unit of Time
    85 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    26556736
    Citation
    Cosman F, Gilchrist N, McClung M, Foldes J, de Villiers T, Santora A, Leung A, Samanta S, Heyden N, McGinnis JP 2nd, Rosenberg E, Denker AE. A phase 2 study of MK-5442, a calcium-sensing receptor antagonist, in postmenopausal women with osteoporosis after long-term use of oral bisphosphonates. Osteoporos Int. 2016 Jan;27(1):377-86. doi: 10.1007/s00198-015-3392-7. Epub 2015 Nov 10.
    Results Reference
    result
    PubMed Identifier
    33606045
    Citation
    Saag K, Cosman F, De Villiers T, Langdahl B, Scott BB, Denker AE, Pong A, Santora AC. Early changes in bone turnover and bone mineral density after discontinuation of long-term oral bisphosphonates: a post hoc analysis. Osteoporos Int. 2021 Sep;32(9):1879-1888. doi: 10.1007/s00198-020-05785-3. Epub 2021 Feb 19.
    Results Reference
    derived

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    MK-5442 in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With an Oral Bisphosphonate (MK-5442-012)

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