Clinical trial NCT00960934: A Dose-Ranging Study of MK-5442 in Postmenopausal Women With Osteoporosis (MK-5442-001)
Official title: A Phase IIb, Randomized, Placebo-Controlled, Dose-Ranging Study of MK-5442 in the Treatment of Postmenopausal Women With Osteoporosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Osteoporosis
Keywords: Osteoporosis
Postmenopausal
MK-5442
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-08-18
Enrollment: 383
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: The purpose of this study was to identify an appropriate dose of

MK-5442 that produced an osteoanabolic effect without causing hypercalcemia in postmenopausal women with osteoporosis.

Detailed description: Amendment 4 of the protocol changed the duration of the study from 2 years to 6 months.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal for at least 5 years
* No history of fragility fracture, unless participant is not willing to take marketed osteoporosis therapy or is not a candidate for marketed osteoporosis therapy
* Agrees not to use medications for osteoporosis except medications associated with the study
* Areal bone mineral density (BMD) T-score \<-2.5 at one or more of the following 4 BMD sites: total hip, femoral neck, trochanter, or lumbar spine and is ≥ -3.5 at all 4 BMD sites. Participants unwilling to take or ineligible for marketed osteoporosis therapy may have one or more areal BMD T-scores of \< -3.5

Exclusion Criteria:

* Unable to undergo dual-energy X-ray absorptiometry (DXA) scan due to obesity (ie, weight \>250 lbs)
* Use of oral bisphosphonates in the 6 months prior to study screening, for more than 3 months in the past 2 years, or lifetime use of more than 6 months
* Use of intravenous bisphosphonates, strontium, or growth hormone at any time
* Use of phenytoin or heparin within 2 weeks prior to Visit 1; use of raloxifene within 6 months prior to Visit 1
* Use of pioglitazone or rosiglitazone at study screening
* Use of estrogen ± progestin, in any form other than vaginal or topical application, for 6 months prior to Study Visit 1
* Prior total thyroidectomy
* Human immunodeficiency virus (HIV)- positive or acquired immune deficiency syndrome (AIDS)-related illness
* History of malignant cancer within 5 years of study screening, except for certain skin or cervical cancers
* History of Paget's disease and/or kidney stones
* An active user of any illicit drug
* History of or active alcohol abuse
* Participated in an investigational drug study within the past 30 days

Primary outcomes:
measure: Least Squares (LS) Mean Percent Change From Baseline to Month 6 in Lumbar Spine Areal Bone Mineral Density (aBMD)
timeFrame: Baseline (BL) and Month 6
measure: Percentage of Participants With Total Serum Calcium Levels Outside the Pre-defined Limits of Change
timeFrame: Baseline through Month 6
measure: Percentage of Participants With Albumin-Corrected Calcium Levels Outside the Pre-defined Limits of Change
timeFrame: Baseline through Month 6
measure: Percentage of Participants With Kidney Stones
timeFrame: Baseline through Month 6
measure: Percentage of Participants With Bone Neoplasms
timeFrame: Baseline through Month 6
Secondary outcomes:
measure: LS Mean Percent Change From Baseline to Month 6 in Total Hip aBMD
timeFrame: Baseline and Month 6
measure: LS Mean Percent Change From Baseline to Month 6 in Femoral Neck aBMD
timeFrame: Baseline and Month 6
measure: LS Mean Percent Change From Baseline to Month 6 in Trochanter aBMD
timeFrame: Baseline and Month 6
measure: LS Mean Percent Change From Baseline to Month 6 in Total Body aBMD
timeFrame: Baseline and Month 6
measure: LS Mean Percent Change From Baseline to Month 6 in Distal One-third Forearm Areal BMD
timeFrame: Baseline and Month 6
measure: LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Hip
timeFrame: Baseline and Month 6
measure: LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Lumbar Spine
timeFrame: Baseline and Month 6
measure: LS Mean Percent Change From Baseline to Month 6 in the Ratio of Urinary N-Telopeptides of Type I Collagen to Creatinine (u-NTx/Cr)
timeFrame: Baseline and Month 6
measure: LS Mean Percent Change From Baseline to Month 6 in Serum C-Terminal Telopeptide Collagen I (s-CTx)
timeFrame: Baseline to Month 6
measure: LS Mean Percent Change From Baseline to Month 6 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP)
timeFrame: Baseline and Month 6
measure: LS Mean Percent Change From Baseline to Month 6 in Serum Procollagen Type I N-Terminal Propeptide (P1NP)
timeFrame: Baseline to Month 6
measure: LS Mean Percent Change From Baseline to Month 6 in Serum Osteocalcin
timeFrame: Baseline and Month 6
Other outcomes:
Locations:
Study officials:
References:
citation: Halse J, Greenspan S, Cosman F, Ellis G, Santora A, Leung A, Heyden N, Samanta S, Doleckyj S, Rosenberg E, Denker AE. A phase 2, randomized, placebo-controlled, dose-ranging study of the calcium-sensing receptor antagonist MK-5442 in the treatment of postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2014 Nov;99(11):E2207-15. doi: 10.1210/jc.2013-4009. Epub 2014 Aug 28.