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

NCT00960934 | Terminated Phase 2 Results

• 2 other identifiers: 5442-0012009-012926-35
• Study Type: interventional
• Target: 383
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Osteoporosis

Keywords

Osteoporosis; Postmenopausal; MK-5442

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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

Secondary Outcomes (12)

• LS Mean Percent Change From Baseline to Month 6 in Total Hip aBMD

  Baseline and Month 6

• LS Mean Percent Change From Baseline to Month 6 in Femoral Neck aBMD

  Baseline and Month 6

• LS Mean Percent Change From Baseline to Month 6 in Trochanter aBMD

  Baseline and Month 6

• LS Mean Percent Change From Baseline to Month 6 in Total Body aBMD

  Baseline and Month 6

• LS Mean Percent Change From Baseline to Month 6 in Distal One-third Forearm Areal BMD

  Baseline and Month 6

Study Arms (6)

MK-5442 2.5 mg

EXPERIMENTAL

Following a 2-week open-label placebo run-in, participants received a daily oral dose of 2.5 mg of MK-5442 for a duration of at least 6 months.

Drug: MK-5442; Drug: Placebo; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium carbonate

MK-5442 5 mg

EXPERIMENTAL

Following a 2-week open-label placebo run-in, participants received a daily oral dose of 5 mg of MK-5442 for a duration of at least 6 months.

Drug: MK-5442; Drug: Placebo; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium carbonate

MK-5442 7.5 mg

EXPERIMENTAL

Following a 2-week open-label placebo run-in, participants received a daily oral dose of 7.5 mg of MK-5442 for a duration of at least 6 months.

Drug: MK-5442; Drug: Placebo; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium carbonate

MK-5442 10 mg

EXPERIMENTAL

Following a 2-week open-label placebo run-in, participants received a daily oral dose of 10 mg of MK-5442 for a duration of at least 6 months.

Drug: MK-5442; Drug: Placebo; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium carbonate

MK-5442 15 mg

EXPERIMENTAL

Following a 2-week open-label placebo run-in, participants received a daily oral dose of 15 mg of MK-5442 for a duration of at least 6 months.

Drug: MK-5442; Drug: Placebo; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium carbonate

Placebo

PLACEBO COMPARATOR

Following a 2-week open-label placebo run-in, participants received a daily oral dose of placebo dose-matched to MK-5442 for a duration of at least 6 months.

Drug: Placebo; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium carbonate

Interventions

MK-5442 DRUG

MK-5442 2.5 mg, 5 mg, 7.5 mg, 10 mg, or 15 mg tablet once daily for at least 6 months.

MK-5442 10 mg; MK-5442 15 mg; MK-5442 2.5 mg; MK-5442 5 mg; MK-5442 7.5 mg

Placebo DRUG

Dose-matched oral placebo to MK-5442

MK-5442 10 mg; MK-5442 15 mg; MK-5442 2.5 mg; MK-5442 5 mg; MK-5442 7.5 mg; Placebo

Vitamin D3 DIETARY_SUPPLEMENT

Vitamin D3, two 400 IU tablets daily throughout the study.

MK-5442 10 mg; MK-5442 15 mg; MK-5442 2.5 mg; MK-5442 5 mg; MK-5442 7.5 mg; Placebo

Calcium carbonate DIETARY_SUPPLEMENT

Participants who had a calcium intake of less than 1200 mg/day at baseline received a daily 500 mg calcium supplement throughout the study.

MK-5442 10 mg; MK-5442 15 mg; MK-5442 2.5 mg; MK-5442 5 mg; MK-5442 7.5 mg; Placebo

Eligibility Criteria

• Age: 45 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related 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 postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2014 Nov;99(11):E2207-15. doi: 10.1210/jc.2013-4009. Epub 2014 Aug 28.

  PMID: 25166719 RESULT

MeSH Terms

Conditions

Osteoporosis

Interventions

JTT 305; Cholecalciferol; Calcium Carbonate

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp and Dohme Corp.

ClinicalTrialDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2009
• First Posted: August 18, 2009
• Study Start: October 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: February 18, 2015
• Results First Posted: October 10, 2012

Record last verified: 2015-02