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

NCT01916720 | Completed Phase 2

• 1 other identifier: 480848/010
• Study Type: interventional
• Target: 103
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

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

  14 +/- 4 days

Secondary Outcomes (4)

• Lp-PLA2 mass in plaque removed during the carotid endarterectomy

  14 +/- 4 days

• Lp-PLA2 mass and activity in blood

  14 +/- days

• Lipid and Non-Lipid Biomarkers in Plasma

  14 +/- days

• Oxidised Lipids and Their Metabolites, and Biomarkers in Plaque

  14 +/- 4 days

Study Arms (3)

SB-480848 40 mg

EXPERIMENTAL

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.

Drug: SB-480848 40 mg; Drug: Placebo

SB-480848 80 mg

EXPERIMENTAL

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.

Drug: SB-480848 80 mg

Matching Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

SB-480848 40 mg DRUG

Study Drug

SB-480848 40 mg

SB-480848 80 mg DRUG

Study Drug

SB-480848 80 mg

Placebo DRUG

Study Drug

Matching Placebo; SB-480848 40 mg

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Related Publications (1)

• 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.

  PMID: 24586490 DERIVED

Related Links

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

MeSH Terms

Conditions

Atherosclerosis

Interventions

darapladib

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2013
• First Posted: August 6, 2013
• Study Start: January 1, 2003
• Primary Completion: July 1, 2003
• Study Completion: July 1, 2003
• Last Updated: December 5, 2016

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will share