A Dose-Ranging Study of MK-5442 in Postmenopausal Women With Osteoporosis (MK-5442-001)

Osteoporosis Clinical Trial

Official title:

A Phase IIb, Randomized, Placebo-Controlled, Dose-Ranging Study of MK-5442 in the Treatment of Postmenopausal Women With Osteoporosis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00960934
• Other study ID #: 5442-001
• Secondary ID: 2009-012926-35
• Status: Terminated
• Phase: Phase 2
• First received: August 17, 2009
• Last updated: February 1, 2015
• Start date: October 2009
• Est. completion date: December 2010

Study information

• Verified date: February 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 383
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years to 85 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• MK-5442
MK-5442 2.5 mg, 5 mg, 7.5 mg, 10 mg, or 15 mg tablet once daily for at least 6 months.
• Placebo
Dose-matched oral placebo to MK-5442

Dietary Supplement:
• Vitamin D3
Vitamin D3, two 400 IU tablets daily throughout the study.
• Calcium carbonate
Participants who had a calcium intake of less than 1200 mg/day at baseline received a daily 500 mg calcium supplement throughout the study.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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 post — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Least Squares (LS) Mean Percent Change From Baseline to Month 6 in Lumbar Spine Areal Bone Mineral Density (aBMD)	Dual Energy X-ray Absorptiometry (DXA) was used to assess and measure aBMD of the lumbar spine. Areal BMD was measured as "areal" density using units of gram (gm) of tissue /centimeter of tissue squared (cm^2).	Baseline (BL) and Month 6	No
Primary	Percentage of Participants With Total Serum Calcium Levels Outside the Pre-defined Limits of Change	Normal serum calcium level is 8-10 mg/dL (2-2.5 mmol/L) with some interlaboratory variation in the reference range, and hypercalcemia is defined as a serum calcium level greater than 10.5 mg/dL (>2.5 mmol/L).; Based on these references, =10.6 mg/dL was predefined in this study as the cut-off for the normal limits of change. Participants with calcium levels =10.6 mg/dL were considered as having a "Tier 1" safety event.	Baseline through Month 6	Yes
Primary	Percentage of Participants With Albumin-Corrected Calcium Levels Outside the Pre-defined Limits of Change	Albumin-Corrected Calcium = ([4 - plasma albumin in g/dL] × 0.8 + serum calcium).; =10.6 mg/dL was predefined in this study as the cut-off for the normal limits of change. Participants with albumin-corrected calcium levels =10.6 mg/dL were considered as having a "Tier 1" safety event.	Baseline through Month 6	Yes
Primary	Percentage of Participants With Kidney Stones	Evidence of kidney stone(s) was considered an event of interest and was prespecified as a "Tier 1" safety event.	Baseline through Month 6	Yes
Primary	Percentage of Participants With Bone Neoplasms	Evidence of bone neoplasm(s) was considered an event of interest and was prespecified as a "Tier 1" safety event.	Baseline through Month 6	Yes
Secondary	LS Mean Percent Change From Baseline to Month 6 in Total Hip aBMD	DXA was used to assess and measure aBMD of the total hip. Areal BMD was measured as "areal" density using units of gram (gm) of tissue /centimeter of tissue squared (cm^2).	Baseline and Month 6	No
Secondary	LS Mean Percent Change From Baseline to Month 6 in Femoral Neck aBMD	DXA was used to assess and measure aBMD of the femoral neck. Areal BMD was measured as "areal" density using units of gram (gm) of tissue /centimeter of tissue squared (cm^2).	Baseline and Month 6	No
Secondary	LS Mean Percent Change From Baseline to Month 6 in Trochanter aBMD	DXA was used to assess and measure aBMD of the trochanter. Areal BMD was measured as "areal" density using units of gram (gm) of tissue /centimeter of tissue squared (cm^2).	Baseline and Month 6	No
Secondary	LS Mean Percent Change From Baseline to Month 6 in Total Body aBMD	DXA was used to assess and measure aBMD of the total body. Areal BMD was measured as "areal" density using units of gram (gm) of tissue /centimeter of tissue squared (cm^2).	Baseline and Month 6	No
Secondary	LS Mean Percent Change From Baseline to Month 6 in Distal One-third Forearm Areal BMD	DXA was used to assess and measure aBMD of the distal 1/3 forearm. Areal BMD was measured as "areal" density using units of gram (gm) of tissue /centimeter of tissue squared (cm^2).	Baseline and Month 6	No
Secondary	LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Hip	Quantitative computed tomography (QCT) technology was used to assess and measure bone mineral content volumetrically (ie, in grams of tissue per centimeter of tissue cubed).	Baseline and Month 6	No
Secondary	LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Lumbar Spine	Quantitative computed tomography (QCT) technology was used at baseline and periodically through out the study to assess and measure bone mineral content volumetrically (ie, in grams of tissue per centimeter of tissue cubed).	Baseline and Month 6	No
Secondary	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)	The ratio of u-NTx to Cr is a biomarker for bone resorption. It is measured in the serum in units of nanomoles (nm) of bone collagen equivalents (BCE)/millimoles of creatinine (Cr).	Baseline and Month 6	No
Secondary	LS Mean Percent Change From Baseline to Month 6 in Serum C-Terminal Telopeptide Collagen I (s-CTx)	C-Terminal Telopeptide Collagen I is used as a serum-marker of bone resorption in the assessment of osteoporosis.	Baseline to Month 6	No
Secondary	LS Mean Percent Change From Baseline to Month 6 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP)	Bone Specific Alkaline Phosphatase is a biomarker of bone formation and is measured in units of microgram (µg)/liter (L).	Baseline and Month 6	No
Secondary	LS Mean Percent Change From Baseline to Month 6 in Serum Procollagen Type I N-Terminal Propeptide (P1NP)	Measurement of P1NP appears to be a sensitive marker of bone formation rate in the assessment of osteoporosis.	Baseline to Month 6	No
Secondary	LS Mean Percent Change From Baseline to Month 6 in Serum Osteocalcin	Serum osteocalcin is a biomarker of bone formation and is measured using units of nanograms (ng) / milliliter (mL).	Baseline and Month 6	No