A Pharmacokinetic Study Of SB-681323 In Subjects With Coronary Heart Disease Undergoing Percutaneous Intervention

Study Overview
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Brief Summary
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Study of SB-681323 (a novel p38 MAPkinase inhibitor) in subjects with documented coronary heart disease (CHD) undergoing elective percutaneous coronary intervention (PCI).

Official Title
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A 28-day, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Anti-inflammatory Effect and Steady-state Pharmacokinetics of SB-681323 (7.5 mg) in Subjects With Coronary Heart Disease (CHD) Undergoing Elective Percutaneous Coronary Interventions (PCI)

Conditions
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Coronary Heart Disease

Intervention / Treatment
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* Drug: SB-681323


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females must be of non-child-bearing potential. Female subjects must have a negative pregnancy test. Subjects scheduled to undergo elective single vessel PCI to be performed within the 6 weeks of diagnostic coronary angiography. Must be on stable dose of statin for = 6 weeks prior to screening, with statin tolerability and LDL <130 mg/dL (3.4 mmol/L) at Screening visit. Must be capable of providing informed consent. Have an hsCRP concentration of >2 mg/L, but < 10 mg/L at screening. Exclusion Criteria: Women who are pregnant or breast feeding. Planned PCI with multi-vessel stenting. Planned PCI with additional revascularization procedures staged at different days during the study period. Planned PCI other than stenting (e.g., atherectomy, PTCA without stenting, etc). Planned PCI of any bypass graft. History of CABG surgery. Planned cardiac or major non-cardiac surgery within the study period. Disabling stroke in the past 6 months. History of chronic viral hepatitis or other chronic hepatic disorders. History of Gilbert's syndrome or elevated bilirubin concentrations at screening. History of increased liver function tests (ALT, AST) due to acute or chronic liver conditions, above the upper limit of normal at screening or in the past 6 months. Renal impairment with serum creatinine >2.0 mg/dl (177umol/L) at Screening, or history of kidney transplant, or a history of contrast nephropathy. Current inadequately controlled hypertension (blood pressure >160 mmHg systolic and/or >100 mmHg diastolic) on a stable dose of antihypertensive medication. Current poorly controlled diabetes mellitus, defined as HbA1c >10% at Screening. History of severe heart failure defined as NYHA class III or IV or those with known severe LV dysfunction (EF<30%) regardless of symptomatic status. History of malignancy within the past 5 years, other than non-melanoma skin cancer. Current life-threatening condition other than vascular disease that may prevent a subject from completing the study. Alcohol or drug abuse within the past 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: SB-681323|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient safety Tolerability Anti-inflammatory effect (high sensitivity C-reactive Protein) |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-inflammatory effect (biomarkers) Endothelial function (peripheral artery tonometry) Pharmacokinetics |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CHD, coronary heart disease, atherosclerosis, inflammation