A Study to Assess the Pharmacokinetics, Safety and Tolerability of Repeat Oral Doses of Darapladib (SB-480848) in Subjects With Severe Renal Impairment

Exclusion Criteria

• •Healthy Subjects
• •A positive pre-study drug/alcohol screen.
• •A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody or positive Hepatitis A IGM antibody result within 3 months of screening.
• •A positive test for HIV antibody.
• •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones
• •History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>14 drinks for males or \>7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
• •The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, or 5 half-lives of the investigational product (whichever is longer).
• •Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• •Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• •Requiring the use of oral or injectable strong CYP3A4 inhibitors (refer to the protocol).
• •Consumption of grapefruit or grapefruit juice \> 8oz within 7 days prior to first dose of study medication.
• •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.
• •History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• •History of anaphylaxis, or anaphylactoid (resembling anaphylaxis) reactions (refer to the protocol). History of severe allergic responses.
• •Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• •Use of oral, injected and implanted hormonal methods of contraception for female subjects.
• •Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
• •Lactating females.
• •Unwillingness or inability to follow the procedures outlined in the protocol.
• •Subjects with a risk of non-compliance in following directions or adhering to study instructions, or any subject that the principal investigator deems unsuitable for participation or continuation.
• •Renally Impaired Subjects
• •Subjects with a life expectancy less than 3 months.
• •Anticipated need for dialysis during the study.
• •A positive pre-study drug/alcohol screen, except where subject has a prescription for pain or anxiolytic medication that would cause a positive test. Investigator should consult medical monitor with patient history before screening if it is known that a patient could have positive test.
• •Subjects with a positive HIV antibody test.
• •Subjects using any concurrent prohibited medication, and/or receiving concurrent therapy that cannot be safely discontinued and is not approved by the Investigator (see protocol for details on prohibited medications).
• •Cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), unstable liver disease (defined by the presence of any of the following felt by the investigator to be related to liver disease and not to other disease processes: ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice), or evidence of abnormal liver function tests (total bilirubin or alkaline phosphatase \>1.5 x upper limit of normal \[ULN\]; or ALT \>2.5 x ULN) or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study.
• •Severe asthma that is poorly controlled on pharmacotherapy.
• •The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• •Requiring the use of oral or injectable strong CYP3A4 inhibitors (refer to protocol). Consumption of grapefruit or grapefruit juice within 7 days prior to first dose of study medication
• •If in the opinion of the Investigator there is an unstable cardiovascular, pulmonary, or hepatic condition present, or any other medical condition which the Investigator and the Medical Monitor considers sufficiently serious to interfere with the conduct, completion, or result of this trial or constitutes an unacceptable risk to the subject.
• •History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• •History of anaphylaxis, or anaphylactoid (resembling anaphylaxis) reactions (refer to the protocol. History of severe allergic responses.
• •Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• •Use of oral, injected and implanted hormonal methods of contraception for female subjects.
• •Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
• •Lactating females
• •History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>14 drinks for males or \>7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
• •Subjects with a risk of non-compliance in following directions or adhering to study restrictions, or any subject that the principal investigator deems unsuitable for participation or continuation.