Clinical Trial: Study to Determine the Effect of 14 Days Dosing With Darapladib (SB-480848) on Carotid Plague Composition in Patients With Planned Carotid Endarterectomy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multi-centre, Randomised, Double-blind, Placebo-controlled, Parallel-group Study to Investigate the Effect of the Lp-PLA2 Inhibitor SB-480848 (40, 80mg od) on Carotid Plaque Composition in Patients

Brief Summary: The primary objective is to determine Lp-PLA2 activity in atherosclerotic carotid plaques after 14 (+/-4) days treatment with darapladib, compared to placebo. Secondary objectives include determination of the change in Lp-PLA2 activity in blood, Lp-PLA2 mass in blood and plaque, specified biomarkers in blood and plaque and their respective correlation's with Lp-PLA2. In addition, the study aims to characterise the PK/PD of repeat oral doses of SB-480848, and safety and tolerability in this population.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome: Lp-PLA2 activity in the atherosclerotic plaque removed during carotid endarterectomy [ Time Frame: 14 +/- 4 days ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Lp-PLA2 mass in plaque removed during the carotid endarterectomy [ Time Frame: 14 +/- 4 days ]
  • Lp-PLA2 mass and activity in blood [ Time Frame: 14 +/- days ]
  • Lipid and Non-Lipid Biomarkers in Plasma [ Time Frame: 14 +/- days ]
    Lipids: total cholesterol, HDL, LDL, and triglycerides Non-Lipids: hsCRP, CD40L, ICAM-1, E-selectin, PAI-1 antibody, PAI-1 antigen, and MMP-9
  • Oxidised Lipids and Their Metabolites, and Biomarkers in Plaque [ Time Frame: 14 +/- 4 days ]
    Oxidised Lipids and Their Metabolites: total lyso-PC, total phospholipid, and total phosphatidylcholine Biomarkers: CD68 (macrophages), CD3 (T cells), CD20 or CD22 (B cells), alpha-actin (smooth muscle cells), CD40L, MMP-2, MMP-9, PAI-1, ICAM-1, IL-6, and Lp-PLA2 (mRNA expression)


Original Secondary Outcome: Same as current

Information By: GlaxoSmithKline

Dates:
Date Received: July 31, 2013
Date Started: January 2003
Date Completion:
Last Updated: December 2, 2016
Last Verified: December 2016