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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Postmenopausal Osteoporosis; Osteoporosis

Treatments: Drug: Placebo to MK-5442; Drug: Vitamin D3; Drug: Placebo to Alendronate; Drug: Alendronate Sodium; Drug: MK-5442; Drug: Calcium carbonate

Study type: Interventional

Funder types: Industry

Identifiers

NCT00996801

5442-012

CTRI/2010/091/000258 (Registry Identifier)

2009-014729-18 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 526 patients

Sex: Female

Ages: 45 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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526 participants in 6 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo to Alendronate

Drug: Calcium carbonate

Drug: Vitamin D3

Drug: Placebo to MK-5442

MK-5442 5 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo to Alendronate

Drug: MK-5442

Drug: Calcium carbonate

Drug: Vitamin D3

MK-5442 7.5 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo to Alendronate

Drug: MK-5442

Drug: Calcium carbonate

Drug: Vitamin D3

MK-5442 10 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo to Alendronate

Drug: MK-5442

Drug: Calcium carbonate

Drug: Vitamin D3

MK-5442 15 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo to Alendronate

Drug: MK-5442

Drug: Calcium carbonate

Drug: Vitamin D3

Alendronate 70 mg

Active Comparator group

Description:

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.

Treatment:

Drug: Alendronate Sodium

Drug: Calcium carbonate

Drug: Vitamin D3

Drug: Placebo to MK-5442