Coronary Heart Disease (CHD)
Conditions
Interventions
Product Code: SB-681323
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: SB-681323
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. Male adults or female adults of non-child-bearing potential aged 18 to 80 years of age at screening. 2. Female Subjects included must have a negative pregnancy test (i.e. serum beta hCG test) and must be of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is surgically sterile via hysterectomy or bilateral ligation or who is post-menopausal. For the purposes of this study, postmenopausal is defined as one year without menses). 3. Subjects who are scheduled to undergo elective single vessel PCI to be performed within the 6 weeks of diagnostic coronary angiography confirming obstructive CHD. 4. Subjects must have been on a stable dose of a statin for = 6 weeks prior to screening, with statin tolerability and LDL 2 mg/L, but =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. Women who are pregnant or breast feeding. 2. Planned PCI with multi-vessel stenting. 3. Planned PCI with additional revascularization procedures staged at different days during the study period. 4. Planned PCI other than stenting (e.g., rotational atherectomy, direct atherectomy, balloon angioplasty without stenting, etc). 5. Planned PCI of any bypass graft. 6. History of CABG surgery. 7. Planned cardiac surgery (e.g., CABG, valve repair or replacement) or planned major non-cardiac surgery within the study period. 8. Disabling stroke in the past 6 months. 9. History of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody), or other chronic hepatic disorders. 10. History of Gilbert's syndrome or elevated bilirubin concentrations. Subjects with a total bilirubin concentration above the upper limit of normal at Screening will be excluded. 11. History of increased liver function tests (ALT, AST) due to acute or chronic liver conditions, above the upper limit of normal in the past 6 months and/or liver function tests (bilirubin, ALT, AST) above the upper limit of normal at Screening. 12. Renal impairment with serum creatinine >2.0 mg/dl (177umol/L) at Screening, or history of kidney transplant, or a history of contrast nephropathy. 13. Current inadequately controlled hypertension (blood pressure >160 mmHg systolic and/or >100 mmHg diastolic) on a stable dose of antihypertensive medication. 14. Current poorly controlled diabetes mellitus, defined as HbA1c >10% at Screen. 15. History of severe heart failure defined as NYHA class III or IV or those with known severe LV dysfunction (EF2 units per day for males and >2 units per day for females or the patient has a positive alcohol screen at the screening visit. 23. Any other subject whom the Investigator deems unsuitable for the study (e.g., due to either medical reasons, laboratory abnormalities, expected study medication non-compliance, or subject’s unwillingness to comply with all study-related study procedures). 24. Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with chronic inflammation (e.g. Inflammatory Bowel Disease). 25. Subjects with chronic infections such as gingivitis, periodontitis, prostatitis, gastritis, and urinary tract infections. 26. Subjects
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To determine the safety and tolerability of SB-681323 administered for 28 days in subjects with CHD on statin therapy. • To estimate the effect of 7.5 mg PO (5mg am, 2.5 mg pm) of SB-681323, compared to placebo, in reducing the acute increase in hsCRP observed following PCI in subjects with angiographically documented CHD. ;Secondary Objective: • To characterise the chronic effect of 7.5 mg PO (5mg am, 2.5 mg pm) of SB-681323, compared to placebo, on stable hsCRP after 28 days of administration. • To evaluate the chronic effect of 7.5 mg PO (5mg am, 2.5 mg pm) of SB-681323, compared to placebo, on the array of soluble biomarkers. • To evaluate the effect of 7.5 mg PO (5mg am, 2.5 mg pm) of SB-681323, compared to placebo, on endothelial function utilizing peripheral arterial tonometry. • To evaluate the pharmacokinetics of 7.5 mg PO (5mg am, 2.5 mg pm) of SB-681323 in subjects under going elective PCI. ;Primary end point(s): • Assessment of the incidence of liver function abnormalities (ALT) in conjunction with the other safety assessments based on the routine laboratory values including creatine kinase. • Baseline corrected hs-CRP concentrations at 2 days after PCI (i.e., 5 days on treatment). | — |
Countries
Belgium, Spain
Outcome results
None listed