Efficacy and Safety of the ACAT Inhibitor CS-505 (Pactimibe) for Reducing the Progression of Carotid Artery Disease. This Study is Also Known as CAPTIVATE.

A Randomized, Double-blind, Stratified, Placebo-controlled, Parallel-group Study of the Efficacy and Safety of the ACAT Inhibitor CS-505 for Reducing the Progression of Atherosclerosis in Subjects With Heterozygous Familial Hypercholesterolemia and Carotid Atherosclerosis Using Carotid Ultrasound (CUS)

The effects of pactimibe versus placebo on the progression of atherosclerosis in the carotid arteries will be assessed using standard ultrasound techniques.

Study Overview

• Status: Terminated
• Conditions: Atherosclerosis; Heterozygous Familial Hypercholesterolemia
• Intervention / Treatment: Drug: Pactimibe sulfate

• Study Type: Interventional
• Enrollment: 796
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
  • Ontario
    • Toronto, Ontario, Canada
  • Quebec
    • Chicoutimi, Quebec, Canada
    • Chomedey Laval, Quebec, Canada
    • Montreal, Quebec, Canada
    • Ste-Foy, Quebec, Canada
• Israel
  • Jerusalem, Israel
• Netherlands
  • Capelle a/d Ijssel, Netherlands
  • Dordrecht, Netherlands
  • Etten-Leur, Netherlands
  • Goes, Netherlands
  • Gorinchem, Netherlands
  • Gouda, Netherlands
  • Groningen, Netherlands
  • Hoorn, Netherlands
  • Leiden, Netherlands
  • Rotterdam, Netherlands
  • Tilburg, Netherlands
  • Zuidoost
    • Amsterdam, Zuidoost, Netherlands
• Norway
  • Oslo, Norway
• South Africa
  • Bellville, South Africa
  • Midrand, South Africa
  • Pretoria, South Africa
• Spain
  • Barcelona, Spain
  • Cordoba, Spain
• Sweden
  • Linkoping, Sweden
  • Stockholm, Sweden
• United Kingdom
  • London, United Kingdom
  • Manchester, United Kingdom
• United States
  • California
    • Santa Ana, California, United States
  • Illinois
    • Chicago, Illinois, United States
  • Maryland
    • Baltimore, Maryland, United States
  • Missouri
    • St. Louis, Missouri, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Texas
    • Houston, Texas, United States
  • Utah
    • Salt Lake City, Utah, United States
  • Washington
    • Seattle, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of heterozygous familial hypercholesterolemia
• Ambulatory male (40 to 75 years, inclusive) or female (45 to 75 years, inclusive) subjects
• Calculated LDL-C level greater than or equal to 100 mg/dL (or 2.5 mmol/L) and triglycerides less than 500 mg/dL (5.65 mmol/L) while on usual and stable lipid-lowering therapy

Exclusion Criteria:

• Breast feeding or lactating women
• Previous organ transplantation
• High-grade stenosis (>75%) or the occlusion of any segment of either carotid artery
• History of carotid endarterectomy, or insertion of carotid artery stent or are scheduled to have either of these procedures

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To demonstrate the effect of pactimibe versus placebo, when added to usual medical care, on the intima-media thickness (IMT) of the carotid arteries in subjects with heterozygous familial hypercholesterolemia (HeFH) and carotid atherosclerosis.

Secondary Outcome Measures

Outcome Measure
To assess the effects of pactimibe versus placebo, when added to usual medical care:
- on the incidence and the time to first occurrence of
cardiovascular events,
- on inflammatory and oxidative markers, such as serum
high-sensitivity C-reactive protein (hsCRP), plasma
interleukin 6 (IL-6), plasma myeloperoxidase (MPO) and
serum nitrotyrosine.
To compare the safety of pactimibe versus placebo, when added to usual medical care, particularly with respect to the incidence of clincal and laboratory adverse events.

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Publications and helpful links

General Publications

• Meuwese MC, de Groot E, Duivenvoorden R, Trip MD, Ose L, Maritz FJ, Basart DC, Kastelein JJ, Habib R, Davidson MH, Zwinderman AH, Schwocho LR, Stein EA; CAPTIVATE Investigators. ACAT inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia: the CAPTIVATE randomized trial. JAMA. 2009 Mar 18;301(11):1131-9. doi: 10.1001/jama.301.11.1131.

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): March 1, 2006
• Study Completion (Actual): March 1, 2006

Study Registration Dates

• First Submitted: September 7, 2005
• First Submitted That Met QC Criteria: September 7, 2005
• First Posted (Estimate): September 9, 2005

Study Record Updates

• Last Update Posted (Estimate): January 18, 2012
• Last Update Submitted That Met QC Criteria: January 16, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Atherosclerosis; Hyperlipoproteinemia Type II
• Other Study ID Numbers: 505-205