Last updated: 11/07/2018 14:28:00

Study to determine the effect of 14 days dosing with darapladib (SB-480848) on carotid plague composition in patients with planned carotid endarterectomy

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GSK study ID
480848/010
See study documents
Clinicaltrials.gov ID
NCT01916720
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Lp-PLA2 activity in the atherosclerotic plaque removed during carotid endarterectomy

Timeframe: 14 +/- 4 days

Secondary outcomes:

Lp-PLA2 mass in plaque removed during the carotid endarterectomy

Timeframe: 14 +/- 4 days

Lp-PLA2 mass and activity in blood

Timeframe: 14 +/- days

Lipid and Non-Lipid Biomarkers in Plasma

Timeframe: 14 +/- days

Oxidised Lipids and Their Metabolites, and Biomarkers in Plaque

Timeframe: 14 +/- 4 days

Interventions:
  • Drug: SB-480848 40 mg
  • Drug: SB-480848 80 mg
  • Drug: Placebo
    • Enrollment:
    103
    Primary completion date:
    2003-31-07
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Atherosclerosis
    Product
    darapladib
    Collaborators
    Not applicable
    Study date(s)
    January 2003 to July 2003
    Type
    Interventional
    Phase
    2

    Participation criteria

    Sex
    Female & Male
    Age
    35+ years
    Accepts healthy volunteers
    No
    • Male or female, >35 years of age
    • Females of childbearing potential must be using approved contraceptive measures
    • Recent myocardial infarction (within the previous 4 weeks)
    • Currently taking corticosteroids, warfarin, digoxin or a potent CYP3A4 inhibitor
    Inclusion and exclusion criteria
    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

    Trial location(s)

    This study does not involve prospective enrollment of participants.

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Refer to study documents

    Recruitment status
    Study complete
    Actual primary completion date
    2003-31-07
    Actual study completion date
    2003-31-07

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

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