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

NCT ID: NCT01916720

Last Updated: 2016-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-01-31
• Study Completion Date: 2003-07-31

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.

Conditions

Atherosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

SB-480848 40 mg

Intervention Type: DRUG

Study Drug

Placebo

Intervention Type: DRUG

Study Drug

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.

Group Type: EXPERIMENTAL

SB-480848 80 mg

Intervention Type: DRUG

Study Drug

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Study Drug

Interventions

SB-480848 40 mg

Study Drug

Intervention Type: DRUG

SB-480848 80 mg

Study Drug

Intervention Type: DRUG

Placebo

Study Drug

Intervention Type: DRUG

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

• Minimum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

References

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.

Reference Type: DERIVED

PMID: 24586490 (View on PubMed)

Study Documents

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

480848/010

Identifier Type: -

Identifier Source: org_study_id