OsteoporosisPhase 2NCT00996801

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

A Phase 2 study testing MK-5442, Alendronate Sodium and Vitamin D3 in people with Osteoporosis and Postmenopausal Osteoporosis, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 45 to 85 years, women only
Conditions the study is for: Osteoporosis, Postmenopausal Osteoporosis
What is being tested?: MK-5442, Alendronate Sodium and Vitamin D3
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 526 participants
Where: No sites listed yet
Study dates: Nov 2009to Jun 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 45 to 85 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 13Show fewer

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

About this study

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

Read the 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.

Conditions: Osteoporosis, Postmenopausal Osteoporosis
Being tested: MK-5442, Placebo to MK-5442, Alendronate Sodium, Vitamin D3, Calcium carbonate
Medical subject headings: Osteoporosis, Osteoporosis, Postmenopausal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK-5442Drug
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-5442Drug
Matching placebo to MK-5442 taken orally, once-daily, for 12 months
Alendronate SodiumDrug
Also called FOSAMAX®
Alendronate tablets 70 mg, taken orally, once-weekly, for 12 months
Vitamin D3Drug
Also called Cholecalciferol
Vitamin D3 (cholecalciferol) administered orally, at a dose of 5600 IU (two tablets, 2800 IU each), once-weekly for 12 months
Calcium carbonateDrug
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 AlendronateDrug
Placebo to alendronate once-weekly for 12 months

Study groups in NCT00996801
Study group	Role	What they receive
Placebo	Placebo comparator	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. Receives: Drug: Placebo to MK-5442; Drug: Vitamin D3; Drug: Calcium carbonate; Drug: Placebo to Alendronate
MK-5442 5 mg	Experimental	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. Receives: Drug: MK-5442; Drug: Vitamin D3; Drug: Calcium carbonate; Drug: Placebo to Alendronate
MK-5442 7.5 mg	Experimental	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. Receives: Drug: MK-5442; Drug: Vitamin D3; Drug: Calcium carbonate; Drug: Placebo to Alendronate
MK-5442 10 mg	Experimental	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. Receives: Drug: MK-5442; Drug: Vitamin D3; Drug: Calcium carbonate; Drug: Placebo to Alendronate
MK-5442 15 mg	Experimental	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. Receives: Drug: MK-5442; Drug: Vitamin D3; Drug: Calcium carbonate; Drug: Placebo to Alendronate
Alendronate 70 mg	Active comparator	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. Receives: Drug: Placebo to MK-5442; Drug: Alendronate Sodium; Drug: Vitamin D3; Drug: Calcium carbonate

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: Baseline and Month 12
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.
Measured: Baseline through Month 12
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).
Measured: Baseline through Month 12
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).
Measured: Baseline through Month 12

Secondary outcomes (14)

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
Measured: Baseline and Month 12
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
Measured: Baseline and Month 12
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
Measured: Baseline and Month 12
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
Measured: Baseline and Month 12
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
Measured: Baseline and Month 12
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.
Measured: Baseline and Month 12
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.
Measured: Baseline and Month 12
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.
Measured: Baseline and Month 12
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.
Measured: Baseline and Month 12
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
Measured: 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)
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).
Measured: Baseline and Month 12
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.
Measured: Baseline and Month 12
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.
Measured: Baseline and Month 12
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).
Measured: Baseline and Month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2009Jun 2011

First posted16 Oct 2009 (estimated)
Study startNov 2009
Primary completionJun 2011
Study completionJun 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for OsteoporosisStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 526 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00996801
Sponsor's protocol ID: 5442-012
Other IDs: 2009-014729-18, CTRI/2010/091/000258, 2009
Status last verified: Jan 2016
First submitted: 15 Oct 2009
Last updated: 22 Jan 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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.
PubMed 26556736
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.
PubMed 33606045

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 22 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00996801
Acronym / sponsor ID: 5442-012
Conditions: Osteoporosis, Postmenopausal Osteoporosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 526 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: Nov 2009
Primary completion: Jun 2011 (actual)
Study completion: Jun 2011 (actual)
First posted: 16 Oct 2009 (estimated)
Results: Posted 16 Nov 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 6

Arm	Type	Receives
Placebo	Placebo comparator	Drug: Placebo to MK-5442, Drug: Vitamin D3, Drug: Calcium carbonate, Drug: Placebo to AlendronateParticipants 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 mg	Experimental	Drug: MK-5442, Drug: Vitamin D3, Drug: Calcium carbonate, Drug: Placebo to AlendronateParticipants 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 mg	Experimental	Drug: MK-5442, Drug: Vitamin D3, Drug: Calcium carbonate, Drug: Placebo to AlendronateParticipants 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 mg	Experimental	Drug: MK-5442, Drug: Vitamin D3, Drug: Calcium carbonate, Drug: Placebo to AlendronateParticipants 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 mg	Experimental	Drug: MK-5442, Drug: Vitamin D3, Drug: Calcium carbonate, Drug: Placebo to AlendronateParticipants 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 mg	Active comparator	Drug: Placebo to MK-5442, Drug: Alendronate Sodium, Drug: Vitamin D3, Drug: Calcium carbonateParticipants 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.

Who may qualify

Ages: 45 to 85 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (13 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MK-5442MK-5442 tablets (randomized to a dose of 5, 7.5, 10 or 15 mg) taken orally, once-daily, for 12 months	Drug	MK-5442 10 mg, MK-5442 15 mg, MK-5442 5 mg, MK-5442 7.5 mg
Placebo to MK-5442Matching placebo to MK-5442 taken orally, once-daily, for 12 months	Drug	Alendronate 70 mg, Placebo
Alendronate SodiumAlso: FOSAMAX®Alendronate tablets 70 mg, taken orally, once-weekly, for 12 months	Drug	Alendronate 70 mg
Vitamin D3Also: CholecalciferolVitamin D3 (cholecalciferol) administered orally, at a dose of 5600 IU (two tablets, 2800 IU each), once-weekly for 12 months	Drug	Alendronate 70 mg, MK-5442 10 mg, MK-5442 15 mg, MK-5442 5 mg, MK-5442 7.5 mg, Placebo
Calcium carbonateParticipants 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	Drug	Alendronate 70 mg, MK-5442 10 mg, MK-5442 15 mg, MK-5442 5 mg, MK-5442 7.5 mg, Placebo
Placebo to AlendronatePlacebo to alendronate once-weekly for 12 months	Drug	MK-5442 10 mg, MK-5442 15 mg, MK-5442 5 mg, MK-5442 7.5 mg, Placebo

Primary outcome

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
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.
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).
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).

14 secondary outcomes

Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD
Time frame: 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
Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD
Time frame: 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
Least Squares Mean Percent Change From Baseline to Month 12 in 1/3 Distal Forearm Areal BMD
Time frame: 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
Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD of the Hip
Time frame: 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
Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Hip
Time frame: 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
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
Least Squares Mean Percent Change From Baseline to Month 12 in Serum N-Terminal Propeptide (s-P1NP)
Time frame: 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
Least Squares Mean Percent Change From Baseline to Month 12 in Serum Osteocalcin
Time frame: Baseline and Month 12

Results and safety

Results posted to the registry on 16 Nov 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	88	68
MK-5442 5 mg	88	72
MK-5442 7.5 mg	88	65
MK-5442 10 mg	87	56
MK-5442 15 mg	88	0
Alendronate 70 mg	87	68

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

Time frame: Baseline and Month 12. Least squares mean (95% Confidence Interval). Unit: percent change

Measure	Placebo n = 81	MK-5442 5 mg n = 82	MK-5442 7.5mg n = 79	MK-5442 10 mg n = 78	Alendronate 70 mg n = 79
Value	-0.36 (-1.37 to 0.66)	-0.67 (-1.67 to 0.33)	-0.52 (-1.56 to 0.52)	-0.53 (-1.61 to 0.56)	1.29 (0.25 to 2.33)

MK-5442 5 mg vs Alendronate 70 mg: Difference in Least Squares Means: -1.96 (95% CI -3.58 to -0.35), p = 0.012, Longitudinal Data Analysis Model
MK-5442 7.5mg vs Alendronate 70 mg: Difference in Least Squares Means: -1.81 (95% CI -3.37 to -0.25), p = 0.019, Longitudinal Data Analysis Model
MK-5442 10 mg vs Alendronate 70 mg: Difference in Least Squares Means: -1.82 (95% CI -3.23 to -0.41), p = 0.019, Longitudinal Data Analysis Model

Population analysed: Full Analysis Set (FAS): participants who received at least one dose of study treatment, had at least one post-randomization observation, and who had baseline data. The MK-5442 15-mg treatment arm was discontinued as a result of Amendment 1 and thus no outcome analyses were performed.

Primary outcome: Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once

Time frame: Baseline through Month 12. Number. Unit: Participants

Measure	Placebo n = 88	MK-5442 5 mg n = 87	MK-5442 7.5 mg n = 88	MK-5442 10 mg n = 87	MK-5442 15 mg n = 88	Alendronate 70 mg n = 84
≥10.6 ng/mL	3	16	19	27	39	7
≥11.1 ng/mL	1	1	4	7	19	1
≥12.1 ng/mL	0	0	0	1	1	0

Population analysed: All Participants as Treated (APaT): all randomized participants who received at least one dose of study treatment.

Primary outcome: Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once

Time frame: Baseline through Month 12. Number. Unit: Participants

Measure	Placebo n = 88	MK-5442 5 mg n = 87	MK-5442 7.5 mg n = 88	MK-5442 10 mg n = 87	MK-5442 15 mg n = 88	Alendronate 70 mg n = 84
≥10.6 ng/mL	1	3	7	13	28	2
≥11.1 ng/mL	1	0	1	3	9	0
≥12.1 ng/mL	0	0	0	1	0	0

Population analysed: All Participants as Treated (APaT): all randomized participants who received at least one dose of study treatment.

Primary outcome: Number of Participants With Predefined Tier 1 Adverse Events

Time frame: Baseline through Month 12. Number. Unit: Participants

Measure	Placebo n = 88	Alendronate 70 mg n = 84
Osteonecrosis of the jaw	0	0
Kidney stones	3	1
Bone neoplasms	0	0

Population analysed: All Participants as Treated (APaT): all randomized participants who received at least one dose of study treatment.

14 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5.0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	6 of 88 (6.8%)	18 of 88 (20.5%)	Not reported
MK-5442 5 mg	5 of 87 (5.7%)	18 of 87 (20.7%)	Not reported
MK-5442 7.5 mg	4 of 88 (4.5%)	26 of 88 (29.5%)	Not reported
MK-5442 10 mg	6 of 87 (6.9%)	32 of 87 (36.8%)	Not reported
MK-5442 15 mg	4 of 88 (4.5%)	28 of 88 (31.8%)	Not reported
Alendronate 70 mg	1 of 88 (1.1%)	10 of 84 (11.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 26556736Cosman 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.
Derived from this study: PubMed 33606045Saag 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MK-5442, Alendronate Sodium and Vitamin D3 in people with Osteoporosis and Postmenopausal Osteoporosis, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD) (time frame: Baseline and Month 12). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00996801, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2016.