Efficacy Study of p38 Kinase Inhibitor to Treat Patients With Atherosclerosis

A 12-Week, Randomized, Semi Double-Blinded Study Evaluating the Effects of Daily Oral High-Dose Atorvastatin or BMS-582949 on Atherosclerotic Plaque Inflammation as Determined by FDG-PET in High Risk Atherosclerotic Patients

The purpose of the study is to determine whether a p38 kinase inhibitor reduces inflammation in atherosclerotic plaque

Study Overview

• Status: Completed
• Conditions: Vascular Diseases
• Intervention / Treatment: Other: Placebo; Drug: Atorvastatin; Drug: Statin; Drug: BMS-582949

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Chiefland, Florida, United States, 32626
      • Southeast Clinical Research, LLC
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center For Clinical Research - Univ Campus
    • Tampa, Florida, United States, 33609
      • Florida Cardiovascular Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Phillip D. Toth, Md
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
    • Madisonville, Kentucky, United States, 42431
      • Commonwealth Biomedical Research, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Mgh Cardiac Mr Pet Ct Program
  • Michigan
    • Troy, Michigan, United States, 48098
      • Troy Internal Medince Pc/Research
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Radiant Research, Inc.
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School Of Medicine Imaging Science Laboratories
  • North Carolina
    • Statesville, North Carolina, United States, 28677
      • The Lipid Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group
    • Cincinnati, Ohio, United States, 45212
      • Metabolic and Atherosclerosis Research Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75231
      • Radiant Research, Inc.
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Mc Allen, Texas, United States, 78503
      • McAllen Heart Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• History of documented atherosclerosis
• LDL between 70 and 130 mg/dL
• Patients receiving stable low- to moderate-dose statin
• BMI 18-37 kg/m²
• Must be able to swallow tablets
• Must be able to medically tolerate the procedures, contrast medium, and medications involved

Exclusion Criteria:

• Statin intolerance
• Renal impairment (serum creatinine > 1.5 mg/dL)
• History of chronic viral hepatitis or other liver dysfunction
• Major infection requiring hospitalization or receipt of IV antibiotics due to an infection within 2 months prior to initiation of study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo + background low to moderate dose statin; Placebo + background low to moderate dose statin Tablets, Oral, 0 mg, once daily, for 12 weeks	Other: Placebo; Drug: Statin
Experimental: BMS-582949 + Background low to moderate dose statin; BMS-582949 + Background low to moderate dose statin Tablets, Oral, 100 mg, once daily for 12 weeks	Drug: Statin; Drug: BMS-582949
Active Comparator: Atorvastatin; Atorvastatin Tablets, oral, 80 mg once daily for 12 weeks	Drug: Atorvastatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
FDG-PET signal of the carotid and/or ascending aorta	at 4 and 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Inflammatory and thrombotic biomarkers	will be measured throughout the 12 weeks of treatment

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Emami H, Vucic E, Subramanian S, Abdelbaky A, Fayad ZA, Du S, Roth E, Ballantyne CM, Mohler ER, Farkouh ME, Kim J, Farmer M, Li L, Ehlgen A, Langenickel TH, Velasquez L, Hayes W, Tawakol A. The effect of BMS-582949, a P38 mitogen-activated protein kinase (P38 MAPK) inhibitor on arterial inflammation: a multicenter FDG-PET trial. Atherosclerosis. 2015 Jun;240(2):490-6. doi: 10.1016/j.atherosclerosis.2015.03.039. Epub 2015 Mar 28.

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: December 10, 2007
• First Submitted That Met QC Criteria: December 10, 2007
• First Posted (Estimate): December 11, 2007

Study Record Updates

• Last Update Posted (Estimate): December 7, 2015
• Last Update Submitted That Met QC Criteria: November 6, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: IM119-014