MK5442 in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With an Oral Bisphosphonate (MK-5442-012-AM1) - Full Text View

Sponsor:	Merck
Information provided by:	Merck
ClinicalTrials.gov Identifier:	NCT00996801

Purpose

This study seeks to demonstrate that additional gain in bone mineral density (BMD) can be achieved by switching to MK5442 from an oral bisphosphonate in participants who have been receiving oral bisphosphonate therapy for at least 3 years. The study was originally planned for 2 years and included efficacy analysis of a 15mg MK-5442 treatment arm. Amendment 1 of the protocol eliminated the 2nd year of the study as well the 15mg arm. Enrollment into the 15mg Mk5442 arm was stopped as a result of the amendment and all subjects who had been randomly assigned to the 15mg MK5442 treatment arm were discontinued from the study.

Condition	Intervention	Phase
Osteoporosis Postmenopausal Osteoporosis	Drug: MK5442 Drug: Placebo to MK5442 Drug: alendronate sodium Drug: Vitamin D3 Drug: Calcium carbonate Drug: Placebo to Alendronate	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Phase IIb, Randomized, Double-Blind, Placebo- and Active-Controlled, Dose-Range-Finding Study to Evaluate the Effects of MK5442 on Bone Mineral Density (BMD) in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With an Oral Bisphosphonate

Resource links provided by NLM:

MedlinePlus related topics: Bone Density Calcium Minerals Osteoporosis Vitamin D

Drug Information available for: Cholecalciferol Calcium Gluconate Calcium carbonate Alendronate sodium

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Change from baseline in lumbar spine areal bone mineral density (BMD) compared to continued alendronate therapy at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percent change from baseline in total hip, femoral neck, trochanter, total body, and 1/3 distal forearm areal bone mineral density (BMD) at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]

Enrollment:	526
Study Start Date:	November 2009
Study Completion Date:	June 2011
Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo to MK5442 and placebo to alendronate Participant will also receive supplemental vitamin D3 and calcium (as needed)	Drug: Placebo to MK5442 Matching placebo to MK5442 once daily for 12 months Drug: Vitamin D3 Two 2800 IU tablets vitamin D3 (cholecalciferol) once weekly for 12 months Drug: Calcium carbonate Participants who have a calcium intake less than 1200mg/day will receive a daily 500mg calcium supplement throughout the study. Drug: Placebo to Alendronate Placebo to alendronate once weekly for 12 months
Experimental: MK5442 5mg and placebo to alendronate Participant will also receive supplemental vitamin D3 and calcium (as needed)	Drug: MK5442 MK5442 tablets (5, 7.5, 10 or 15 mg) once daily for 12 months Drug: Vitamin D3 Two 2800 IU tablets vitamin D3 (cholecalciferol) once weekly for 12 months Drug: Calcium carbonate Participants who have a calcium intake less than 1200mg/day will receive a daily 500mg calcium supplement throughout the study. Drug: Placebo to Alendronate Placebo to alendronate once weekly for 12 months
Experimental: MK5442 7.5mg and placebo to alendronate Participant will also receive supplemental vitamin D3 and calcium (as needed)	Drug: MK5442 MK5442 tablets (5, 7.5, 10 or 15 mg) once daily for 12 months Drug: Vitamin D3 Two 2800 IU tablets vitamin D3 (cholecalciferol) once weekly for 12 months Drug: Calcium carbonate Participants who have a calcium intake less than 1200mg/day will receive a daily 500mg calcium supplement throughout the study. Drug: Placebo to Alendronate Placebo to alendronate once weekly for 12 months
Experimental: MK5442 10mg and placebo to alendronate Participant will also receive supplemental vitamin D3 and calcium (as needed)	Drug: MK5442 MK5442 tablets (5, 7.5, 10 or 15 mg) once daily for 12 months Drug: Vitamin D3 Two 2800 IU tablets vitamin D3 (cholecalciferol) once weekly for 12 months Drug: Calcium carbonate Participants who have a calcium intake less than 1200mg/day will receive a daily 500mg calcium supplement throughout the study. Drug: Placebo to Alendronate Placebo to alendronate once weekly for 12 months
Experimental: MK5442 15 mg and placebo to alendronate Participant will also receive supplemental vitamin D3 and calcium (as needed)	Drug: MK5442 MK5442 tablets (5, 7.5, 10 or 15 mg) once daily for 12 months Drug: Vitamin D3 Two 2800 IU tablets vitamin D3 (cholecalciferol) once weekly for 12 months Drug: Calcium carbonate Participants who have a calcium intake less than 1200mg/day will receive a daily 500mg calcium supplement throughout the study. Drug: Placebo to Alendronate Placebo to alendronate once weekly for 12 months
Active Comparator: Alendronate 70mg and placebo to MK5442 Participant will also receive supplemental vitamin D3 and calcium (as needed)	Drug: Placebo to MK5442 Matching placebo to MK5442 once daily for 12 months Drug: alendronate sodium Alendronate tablets 70mg once weekly for 12 months Other Name: Fosamax Drug: Vitamin D3 Two 2800 IU tablets vitamin D3 (cholecalciferol) once weekly for 12 months Drug: Calcium carbonate Participants who have a calcium intake less than 1200mg/day will receive a daily 500mg calcium supplement throughout the study.

Eligibility

Ages Eligible for Study:	45 Years to 85 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Has been taking an oral bisphosphonate for osteoporosis for at least 3 years within the past 4 years, and the bisphosphonate must have been alendronate for the most recent 12 months, and is currently taking alendronate.
Has a BMD T-score that is <=-1.5 at one or more of the following 4 BMD 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, an a BMD T-score that is ≤-2.5 at one or more of the following 4 BMD sites; lumbar spine, femoral neck, trochanter, and total hip, AND a BMD T-score at all of these sites that is ≥ -4.0
Has been postmenopausal for at least 5 years

Exclusion Criteria:

Is unable to have dual-emission X-ray absorptiometry (DXA) performed due to obesity
Has received intravenous (IV) bisphosphonates, fluoride treatment at a dose >1 mg/day for more than 2 weeks, strontium, growth hormone, a cathepsin K inhibitor, or a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor at any time in the past
Has received 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
Has used 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
Is taking more than 10,000 IU vitamin A daily or more than 5,000 IU vitamin D daily
Has had a total thyroidectomy
Has any history of Paget's disease
Is HIV positive
Has a history of cancer in the last 5 years, except certain skin or cervical cancers
Has a history of major upper GI mucosal erosive disease
Is unable to adhere to dosing instructions for alendronate in regard to fasting and positioning
Is not ambulatory

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	Vice President of Late Stage Development, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00996801 History of Changes
Other Study ID Numbers:	MK-5442-012, 2009_675
Study First Received:	October 15, 2009
Last Updated:	July 14, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Merck:

Osteoporosis
Postmenopausal

Additional relevant MeSH terms:

Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Calcium, Dietary
Cholecalciferol
Diphosphonates
Vitamin D
Ergocalciferols

Alendronate
Calcium Carbonate
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on May 24, 2012