Clinical trial NCT00996801: MK-5442 in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With an Oral Bisphosphonate (MK-5442-012)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoporosis
Postmenopausal Osteoporosis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-10-16
Enrollment: 526
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD)
timeFrame: Baseline and Month 12
measure: Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once
timeFrame: Baseline through Month 12
measure: Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once
timeFrame: Baseline through Month 12
measure: Number of Participants With Predefined Tier 1 Adverse Events
timeFrame: Baseline through Month 12
Secondary outcomes:
measure: Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD
timeFrame: Baseline and Month 12
measure: Least Squares Mean Percent Change From Baseline to Month 12 in Femoral Neck Areal BMD
timeFrame: Baseline and Month 12
measure: Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD
timeFrame: Baseline and Month 12
measure: Least Squares Mean Percent Change From Baseline to Month 12 in Total Body Areal BMD
timeFrame: Baseline and Month 12
measure: Least Squares Mean Percent Change From Baseline to Month 12 in 1/3 Distal Forearm Areal BMD
timeFrame: Baseline and Month 12
measure: Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD (vBMD) of the Lumbar Spine
timeFrame: Baseline and Month 12
measure: Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD of the Hip
timeFrame: Baseline and Month 12
measure: Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Lumbar Spine
timeFrame: Baseline and Month 12
measure: Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Hip
timeFrame: Baseline and Month 12
measure: Least Squares Mean Percent Change From Baseline to Month 12 in Urinary-N Telopeptides of Type 1 Collagen (u-NTx)
timeFrame: Baseline and Month 12
measure: Least Squares Mean Percent Change From Baseline to Month 12 in Serum C-Terminal Propeptide of Type 1 Collagen (s-CTx)
timeFrame: Baseline and Month 12
measure: Least Squares Mean Percent Change From Baseline to Month 12 in Serum N-Terminal Propeptide (s-P1NP)
timeFrame: Baseline and Month 12
measure: Least Squares Mean Percent Change From Baseline to Month 12 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP)
timeFrame: Baseline and Month 12
measure: Least Squares Mean Percent Change From Baseline to Month 12 in Serum Osteocalcin
timeFrame: Baseline and Month 12
Other outcomes:
Locations:
Study officials:
References:
citation: 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.
citation: 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.