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Completed

NCT Number: NCT00996801

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

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.

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Key information

Conditions

Osteoporosis Bone Diseases Bone Diseases, Metabolic Metabolic Diseases Musculoskeletal Diseases Nutritional and Metabolic Diseases Osteoporosis, Postmenopausal Postmenopausal Osteoporosis

Age range

45 year–85 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

MK-5442

Drug

MK-5442 tablets (randomized to a dose of 5, 7.5, 10 or 15 mg) taken orally, once-daily, for 12 months

Placebo to MK-5442

Drug

Matching placebo to MK-5442 taken orally, once-daily, for 12 months

Alendronate sodium

Drug

Alendronate tablets 70 mg, taken orally, once-weekly, for 12 months

Other names: FOSAMAX®

Vitamin D3

Drug

Vitamin D3 (cholecalciferol) administered orally, at a dose of 5600 IU (two tablets, 2800 IU each), once-weekly for 12 months

Other names: Cholecalciferol

Calcium Carbonate

Drug

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

Drug

Placebo to alendronate once-weekly for 12 months

Primary outcomes

  1. Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD)

    Time frame: 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

  2. Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once

    Time frame: 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.

  3. Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once

    Time frame: 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).

  4. Number of Participants With Predefined Tier 1 Adverse Events

    Time frame: 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 outcomes

  1. Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD

    Time frame: 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

  2. Least Squares Mean Percent Change From Baseline to Month 12 in Femoral Neck Areal BMD

    Time frame: 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

  3. Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD

    Time frame: 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

  4. Least Squares Mean Percent Change From Baseline to Month 12 in Total Body Areal BMD

    Time frame: 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

  5. Least Squares Mean Percent Change From Baseline to Month 12 in 1/3 Distal Forearm Areal BMD

    Time frame: 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

  6. Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD (vBMD) of the Lumbar Spine

    Time frame: 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.

  7. Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD of the Hip

    Time frame: 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.

  8. Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Lumbar Spine

    Time frame: 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.

  9. Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Hip

    Time frame: 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.

  10. Least Squares Mean Percent Change From Baseline to Month 12 in Urinary-N Telopeptides of Type 1 Collagen (u-NTx)

    Time frame: 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

  11. Least Squares Mean Percent Change From Baseline to Month 12 in Serum C-Terminal Propeptide of Type 1 Collagen (s-CTx)

    Time frame: 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).

  12. Least Squares Mean Percent Change From Baseline to Month 12 in Serum N-Terminal Propeptide (s-P1NP)

    Time frame: 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.

  13. Least Squares Mean Percent Change From Baseline to Month 12 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP)

    Time frame: Baseline and Month 12

    Bone Specific Alkaline Phosphatase is a biomarker of bone formation and is measured in units of μg/L.

  14. Least Squares Mean Percent Change From Baseline to Month 12 in Serum Osteocalcin

    Time frame: Baseline and Month 12

    Serum osteocalcin is a biomarker of bone formation and is measured using units of nanograms (ng) / milliliter

    (mL).

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study 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

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Oct 16, 2009
Registry last updated
Jan 22, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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