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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Atherosclerosis

Treatments: Drug: SB-480848 80 mg; Drug: SB-480848 40 mg; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01916720

480848/010

Details and patient eligibility

About

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.

Enrollment: 103 patients

Sex: All

Ages: 35+ years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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103 participants in 3 patient groups, including a placebo group

SB-480848 40 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: SB-480848 40 mg

SB-480848 80 mg

Experimental group

Description:

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.

Treatment:

Drug: SB-480848 80 mg

Matching Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo