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

Condition(s) targeted: Osteoporosis; Postmenopausal Osteoporosis

Intervention: MK-5442 (Drug); Placebo to MK-5442 (Drug); Alendronate Sodium (Drug); Vitamin D3 (Drug); Calcium carbonate (Drug); Placebo to Alendronate (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Merck Sharp & Dohme Corp.

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.

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome:

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

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

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

Number of Participants With Predefined Tier 1 Adverse Events

Secondary outcome:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

Minimum age: 45 Years. Maximum age: 85 Years. Gender(s): Female.

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

Starting date: November 2009
Last updated: November 20, 2014