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

Atherosclerosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01916720
• Other study ID #: 480848/010
• Status: Completed
• Phase: Phase 2
• First received: July 31, 2013
• Last updated: December 2, 2016
• Start date: January 2003
• Est. completion date: July 2003

Study information

• Verified date: December 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: July 2003
• Est. primary completion date: July 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

Drug:
• SB-480848 40 mg
Study Drug
• SB-480848 80 mg
Study Drug
• Placebo
Study Drug

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lp-PLA2 activity in the atherosclerotic plaque removed during carotid endarterectomy		14 +/- 4 days	No
Secondary	Lp-PLA2 mass in plaque removed during the carotid endarterectomy		14 +/- 4 days	No
Secondary	Lp-PLA2 mass and activity in blood		14 +/- days	No
Secondary	Lipid and Non-Lipid Biomarkers in Plasma	Lipids: total cholesterol, HDL, LDL, and triglycerides Non-Lipids: hsCRP, CD40L, ICAM-1, E-selectin, PAI-1 antibody, PAI-1 antigen, and MMP-9	14 +/- days	No
Secondary	Oxidised Lipids and Their Metabolites, and Biomarkers in Plaque	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)	14 +/- 4 days	No

External Links

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