Clinical trial NCT01916720: Study to Determine the Effect of 14 Days Dosing With Darapladib (SB-480848) on Carotid Plague Composition in Patients With Planned Carotid Endarterectomy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atherosclerosis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-08-06
Enrollment: 103
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Lp-PLA2 activity in the atherosclerotic plaque removed during carotid endarterectomy
timeFrame: 14 +/- 4 days
Secondary outcomes:
measure: Lp-PLA2 mass in plaque removed during the carotid endarterectomy
timeFrame: 14 +/- 4 days
measure: Lp-PLA2 mass and activity in blood
timeFrame: 14 +/- days
measure: Lipid and Non-Lipid Biomarkers in Plasma
timeFrame: 14 +/- days
measure: Oxidised Lipids and Their Metabolites, and Biomarkers in Plaque
timeFrame: 14 +/- 4 days
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Johnson JL, Shi Y, Snipes R, Janmohamed S, Rolfe TE, Davis B, Postle A, Macphee CH. Effect of darapladib treatment on endarterectomy carotid plaque lipoprotein-associated phospholipase A2 activity: a randomized, controlled trial. PLoS One. 2014 Feb 20;9(2):e89034. doi: 10.1371/journal.pone.0089034. eCollection 2014.