Phase 2 N=526 Randomized Double-blind Treatment

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

Osteoporosis · Postmenopausal Osteoporosis

Bottom Line

View on ClinicalTrials.gov: NCT00996801 ↗

Enrolled (actual)

526

Serious AEs

4.9%

Results posted

Nov 2012

Primary outcome: Primary: Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD) — -0.36; -0.67; -0.52; -0.53 percent change — p=0.012

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: MK-5442 (Drug); Placebo to MK-5442 (Drug); Alendronate Sodium (Drug); Vitamin D3 (Drug); Calcium carbonate (Drug); Placebo to Alendronate (Drug)
Age: Adult, Older Adult · 45+ yrs
Sex: Female
Sponsor: Merck Sharp & Dohme LLC
Primary completion: Jun 2011

Outcome Measures

Outcome	Result	p-value
PRIMARY Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD)	-0.36; -0.67; -0.52; -0.53; 1.29	0.012 sig
PRIMARY Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once	3; 16; 19; 27; 39; 7	—
PRIMARY Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once	1; 3; 7; 13; 28; 2	—
PRIMARY Number of Participants With Predefined Tier 1 Adverse Events	0; 0; 0; 0; 0; 0	—
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD	-1.44; -2.18; -2.16; -1.66; 0.46	<0.001 sig
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in Femoral Neck Areal BMD	-1.26; -2.12; -1.37; -1.84; -0.08	0.002 sig
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD	-0.30; -1.56; -1.50; -1.52; 1.68	<0.001 sig
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in Total Body Areal BMD	-0.17; -0.54; -0.69; -1.10; 0.82	0.001 sig
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in 1/3 Distal Forearm Areal BMD	-0.54; -1.38; -0.92; -2.01; -0.91	0.680
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD (vBMD) of the Lumbar Spine	0.18; -0.25; 0.08; 0.16; 1.74	0.094
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD of the Hip	-0.02; 0.76; 0.81; 0.27; 1.23	0.824
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Lumbar Spine	-0.67; -3.41; 14.66; -0.34; 12.80	0.227
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Hip	0.10; -0.49; -0.15; -0.16; 0.99	0.010 sig
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in Urinary-N Telopeptides of Type 1 Collagen (u-NTx)	63.64; 86.51; 83.32; 107.44; 0.18	<0.001 sig
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in Serum C-Terminal Propeptide of Type 1 Collagen (s-CTx)	165.80; 214.09; 227.07; 251.08; 26.78	<0.001 sig
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in Serum N-Terminal Propeptide (s-P1NP)	68.61; 127.18; 125.69; 163.96; -5.85	<0.001 sig
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP)	29.51; 50.04; 49.98; 51.64; -3.83	<0.001 sig
SECONDARY Least Squares Mean Percent Change From Baseline to Month 12 in Serum Osteocalcin	—	—

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.

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00996801). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.