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

Inclusion Criteria:

- A male or female is eligible to enter and participate in this study if he/she is: A
healthy subject with normal renal function: Healthy as determined by a responsible
and experienced physician, based on a medical evaluation including medical history,
physical examination, laboratory tests and cardiac monitoring. A subject with
clinical abnormalities or laboratory parameters outside the reference range for the
population being studied may be included only if the Investigator and the GSK Medical
Monitor agree that the finding is unlikely to introduce additional risk factors and
will not interfere with the study procedures; Estimated Creatinine clearance ≥
90mL/min calculated by Cockcroft-Gault equation using serum creatinine OR A renally
impaired subject - To be classified as renally impaired, subjects must have: An
estimated Glomerular Filtration Rate (eGFR) of <30 ml/min /1.73 m2 using the four
variable Modification of Diet in Renal Disease (MDRD) equation.

- Age between 18 and 75 years inclusive, at the time of signing the informed consent.

- A female subject is eligible to participate if she is of: Non-childbearing potential
defined as pre-menopausal females with a documented tubal ligation or hysterectomy;
or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable
cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml
and estradiol < 40 pg/ml (<140pmol/L) is confirmatory]; Child-bearing potential and
agrees to use one of the contraception methods listed in the protocol for an
appropriate period of time (as determined by the product label or investigator) prior
to the start of dosing to sufficiently minimize the risk of pregnancy at that point.
Female subjects must agree to use contraception until the final follow-up visit (35 ±
7 days after last dose of investigational product)

- Body mass index (BMI) within the range of 19.0-38.0 kg/m2 (inclusive)

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

- QTcF ≤ 480 msec in all subjects, including those with bundle branch block at
screening ECG.

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.