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

This study has been completed.
Information provided by (Responsible Party):
GlaxoSmithKline Identifier:
First received: July 31, 2013
Last updated: August 22, 2013
Last verified: August 2013
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.

Condition Intervention Phase
Drug: SB-480848 40 mg
Drug: SB-480848 80 mg
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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 With Carotid Artery Disease and Planned Carotid Endarterectomy, Stratified for Statin Use and Gender, After 14+/-4 Days Treatment

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Lp-PLA2 activity in the atherosclerotic plaque removed during carotid endarterectomy [ Time Frame: 14 +/- 4 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Lp-PLA2 mass in plaque removed during the carotid endarterectomy [ Time Frame: 14 +/- 4 days ] [ Designated as safety issue: No ]
  • Lp-PLA2 mass and activity in blood [ Time Frame: 14 +/- days ] [ Designated as safety issue: No ]
  • Lipid and Non-Lipid Biomarkers in Plasma [ Time Frame: 14 +/- days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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)

Enrollment: 103
Study Start Date: January 2003
Study Completion Date: July 2003
Primary Completion Date: July 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SB-480848 40 mg
SB-480848 40 milligrams (mg) once a day (od) for 14 +/- 4 days followed by carotid endarterectomy. SB-480848 40 mg was administered as 2 SB-480848 20 mg tablets plus 2 placebo tablets.
Drug: SB-480848 40 mg
Study Drug
Drug: Placebo
Study Drug
Experimental: SB-480848 80 mg
SB-480848 80 mg od for 14 +/- 4 days followed by carotid endarterectomy.SB-480848 80 mg was administered as 4 20 mg SB-480848 tablets.
Drug: SB-480848 80 mg
Study Drug
Placebo Comparator: Matching Placebo
Placebo for 14 +/- 4 days followed by carotid endarterectomy. Placebo was administered as 4 placebo tablets. Placebo tablets were identical in appearance to the SB-480848 20 mg tablets.
Drug: Placebo
Study Drug


Ages Eligible for Study:   35 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male or female, >35 years of age
  • Females of childbearing potential must be using approved contraceptive measures
  • Male patients must be willing to abstain from sexual intercourse or use a form of contraception if engaging in sexual intercourse with a woman who could become pregnant
  • Planned carotid endarterectomy within a timeframe compatible with recruitment for the study and able to comply with the requirements of the study, as deemed by the investigator
  • Written, informed consent to participate

Exclusion Criteria:

  • Recent myocardial infarction (within the previous 4 weeks)
  • Currently taking corticosteroids, warfarin, digoxin or a potent CYP3A4 inhibitor
  • Recent (<3 months) or ongoing acute infection or significant trauma associated with bruising and/or taking antibiotics. Prophylactic antibiotics for surgery are allowed
  • Change in dose of lipid-lowering therapy during the previous 4 weeks from randomisation
  • History of chronic liver disease (e.g. cirrhosis, hepatitis) OR ALT OR AST ≥1.5 times the upper limit of normal (ULN) at screening
  • Diagnosis of systemic lupus erythematosis (SLE) or rheumatoid arthritis (RA)
  • Clinically significant anaemia
  • History of severe renal impairment (serum creatinine >1.8mg/dL)
  • Unstable angina
  • History of asthma , anaphylaxis or anaphylactoid reactions, severe allergic responses
  • Abuse of alcohol or drugs within the last 6 months
  • Any factor or clinical disease state that, in the investigator's opinion, would preclude completion of a safe surgical procedure and/or completion of the study
  • Use of an investigational drugs within 30 days or 5 half-lives of their last dose prior to starting the study, whichever is the longest
  Contacts and Locations
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Please refer to this study by its identifier: NCT01916720

Sponsors and Collaborators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: GlaxoSmithKline Identifier: NCT01916720     History of Changes
Other Study ID Numbers: 480848/010 
Study First Received: July 31, 2013
Last Updated: August 22, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases processed this record on October 26, 2016