chronic Coronary Heart Disease (cCHD)
Conditions
Interventions
Product Name: darapladib
Product Code: SB-480848
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: darapladib
Current Sponsor code: SB-480848
Concentration unit: mg milligram(s)
Concentrati
Sponsors
GlaxoSmithKline Research & Development, Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent prior to beginning study-related procedures (subject must understand the aims, investigational procedures and possible consequences of the study). 2. Male or female aged at least 18 years, inclusive, at screening. Female subjects must be post-menopausal or using a highly effective method for avoidance of pregnancy. The decision to include or exclude women of childbearing potential may be made at the discretion of the investigator in accordance with local practice in relation to adequate contraception. 3. Current treatment with statin therapy unless not indicated according to treatment guidelines or contraindicated in the opinion of the investigator. 4. Chronic CHD documented by at least one of the following: a.prior MI (>1 month prior to randomization). b. prior coronary revascularization procedure [percutaneous coronary intervention (PCI) > 1 month prior to randomization or coronary artery bypass graft (CABG) >3 months prior to randomization]. c. multivessel CHD involving major epicardial coronary arteries confirmed by coronary angiography at any time (without revascularization). AND 5. At least one of the following additional predictors of CV risk [a through f]: a. age >60 years at randomization. b. diabetes mellitus requiring pharmacotherapy. c. HDL-C 3 months. OR • chronic CHD and peripheral arterial disease (PAD). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Planned coronary revascularization (PCI or CABG) or any other major surgical procedure. 2. Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones) or evidence of abnormal liver function tests [total bilirubin or alkaline phosphatase >1.5 x upper limit of normal (ULN); or ALT or AST >2.5 x ULN] or other hepatic abnormalities that in the opinion of the Investigator would preclude the subject from participation in the study. 3. Severe renal impairment (eGFR <30 mL/min/1.73 m2) or history of nephrectomy or kidney transplant (regardless of renal function). 4. Current severe heart failure (New York Heart Association class III or IV). 5. Poorly controlled hypertension despite lifestyle modifications and pharmacotherapy. 6. Any life-threatening condition with life expectancy <2 years, other than vascular disease, that might prevent the subject from completing the study (e.g., very severe chronic airways disease, known human immunodeficiency virus [HIV] positive, or cancer in the past five years other than non-melanoma skin cancer). 7. Severe asthma that is poorly controlled on pharmacotherapy. 8. Positive pregnancy test (all female subjects of childbearing potential must have a urine B-human chorionic gonadotropin [hCG] pregnancy test performed at Screening and/or within 7 days prior to randomization) or is known to be pregnant or lactating. 9. History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses. 10. Alcohol or drug abuse within the past 6 months, or current mental condition (psychiatric disorder, senility or dementia), which may affect study compliance or prevent understanding of the aims, investigational procedures or possible consequences of the study. 11. Current or planned chronic administration of strong oral or injectable cytochrome P-450 isoenzyme 3A4 (CYP3A4) inhibitors. 12. Subjects with both parents of Japanese, Chinese, or Korean ancestry must have a blood sample collected for assessment of Lp-PLA2 activity by the central laboratory prior to randomization. Those with Lp-PLA2 activity </=10 nmol/min/mL will be excluded from participation in the study. 13. Previous exposure to darapladib (SB-480848). 14. Use of another investigational product within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of darapladib or matching placebo. 15. Currently in a study of an investigational device. 16. Any other reason the investigator deems the subject to be unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate clinical efficacy of long-term treatment with darapladib Enteric Coated tablets, 160 mg (oral once daily dose) as compared to placebo when added to standard of care in a chronic Coronary Heart Disease (CHD) patient population on the incidence of first occurrence of the composite of Major Adverse Cardiovascular Events (MACE) (cardiovascular death, non-fatal Myocardial Infarction (MI), non-fatal stroke).;Secondary Objective: The secondary objectives are to evaluate the efficacy of darapladib on major and total coronary events (including CHD death, non-fatal MI, urgent and non-urgent coronary revascularization, or hospitalization for unstable angina), individual components of MACE and all-cause mortality. Additional safety and efficacy parameters including relations to and changes of biomarkers of CV risk, health economic outcomes, and adverse events (AEs) will also be evaluated.;Primary end point(s): The primary efficacy endpoint is the time to the first occurrence of any component of the composite of major adverse cardiovascular events (MACE: CV death, non-fatal MI, or non-fatal stroke) in a chronic CHD population treated with darapladib enteric coated tablets, 160 mg compared with placebo. | — |
Countries
Belgium, Bulgaria, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Italy, Netherlands, Poland, Slovakia, Spain, Sweden, United Kingdom
Outcome results
None listed