- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00996801
MK-5442 in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With an Oral Bisphosphonate (MK-5442-012)
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 Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: 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.
|
Matching placebo to MK-5442 taken orally, once-daily, for 12 months
Vitamin D3 (cholecalciferol) administered orally, at a dose of 5600 IU (two tablets, 2800 IU each), once-weekly for 12 months
Other Names:
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
|
Experimental: 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.
|
Vitamin D3 (cholecalciferol) administered orally, at a dose of 5600 IU (two tablets, 2800 IU each), once-weekly for 12 months
Other Names:
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
MK-5442 tablets (randomized to a dose of 5, 7.5, 10 or 15 mg) taken orally, once-daily, for 12 months
|
Experimental: 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.
|
Vitamin D3 (cholecalciferol) administered orally, at a dose of 5600 IU (two tablets, 2800 IU each), once-weekly for 12 months
Other Names:
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
MK-5442 tablets (randomized to a dose of 5, 7.5, 10 or 15 mg) taken orally, once-daily, for 12 months
|
Experimental: 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.
|
Vitamin D3 (cholecalciferol) administered orally, at a dose of 5600 IU (two tablets, 2800 IU each), once-weekly for 12 months
Other Names:
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
MK-5442 tablets (randomized to a dose of 5, 7.5, 10 or 15 mg) taken orally, once-daily, for 12 months
|
Experimental: 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.
|
Vitamin D3 (cholecalciferol) administered orally, at a dose of 5600 IU (two tablets, 2800 IU each), once-weekly for 12 months
Other Names:
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
MK-5442 tablets (randomized to a dose of 5, 7.5, 10 or 15 mg) taken orally, once-daily, for 12 months
|
Active Comparator: 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.
|
Matching placebo to MK-5442 taken orally, once-daily, for 12 months
Vitamin D3 (cholecalciferol) administered orally, at a dose of 5600 IU (two tablets, 2800 IU each), once-weekly for 12 months
Other Names:
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
Alendronate tablets 70 mg, taken orally, once-weekly, for 12 months
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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 |
Baseline and Month 12
|
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. |
Baseline through Month 12
|
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). |
Baseline through Month 12
|
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).
|
Baseline through Month 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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 |
Baseline and Month 12
|
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 |
Baseline and Month 12
|
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 |
Baseline and Month 12
|
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 |
Baseline and Month 12
|
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 |
Baseline and Month 12
|
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.
|
Baseline and Month 12
|
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.
|
Baseline and Month 12
|
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.
|
Baseline and Month 12
|
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.
|
Baseline and Month 12
|
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 |
Baseline and Month 12
|
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).
|
Baseline and Month 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.
|
Baseline and Month 12
|
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.
|
Baseline and Month 12
|
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). |
Baseline and Month 12
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Musculoskeletal Diseases
- Bone Diseases
- Bone Diseases, Metabolic
- Osteoporosis
- Osteoporosis, Postmenopausal
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Gastrointestinal Agents
- Micronutrients
- Vitamins
- Bone Density Conservation Agents
- Calcium-Regulating Hormones and Agents
- Antacids
- Vitamin D
- Cholecalciferol
- Calcium
- Alendronate
- Calcium Carbonate
Other Study ID Numbers
- 5442-012
- 2009-014729-18 (EudraCT Number)
- CTRI/2010/091/000258 (Registry Identifier: CTRI)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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