Pharmacokinetic Interaction of Darapladib and CYP 3A4 in Healthy Subjects

Inclusion Criteria:

- Male or female aged between 18 and 65 years of age inclusive, at the time of signing
the informed consent.

- Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and ECG.

- A subject with an alanine aminotransferase (ALT), aspartate aminotransferase (AST),
alkaline phosphatase or bilirubin laboratory result outside the reference range may
be included only if both the Investigator and the GSK Medical Monitor agree and
document that the finding is unlikely to introduce additional risk factors and will
not interfere with the study procedures.

- Body mass index within the range 19-37 kilogram per meter square (kg/m2) (inclusive).

- A female subject is eligible to participate if she is of: non-childbearing potential
defined as pre-menopausal females with tubal ligation or hysterectomy or
postmenopausal defined as 12 months of spontaneous amenorrhea; child-bearing
potential and is abstinent or agrees to use the appropriate contraception methods 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; child-bearing potential and has only same-sex partners, when this is her
preferred and usual lifestyle.

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

- Single QTcF (corrected QT calculated using Fridericia's formula)< 450 milliseconds

Exclusion Criteria:

- 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 milliliter [mL]) of beer, 5 ounces (150
mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- History of sensitivity to any of the study medications, including midazolam and
flumazenil, 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.

- Any contraindications for midazolam or flumazenil administration.

- Any condition that, in the opinion of the investigator, presents undue risk from the
study medications, including midazolam and flumazenil, or procedures.

- Requiring the use of oral or injectable strong CYP3A4 inhibitors or use of other
CYP3A4 inhibitor/inducers within 14 days prior to dosing.

- History of anaphylaxis, anaphylactoid reactions or severe allergic response.

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening

- A positive pre-study drug/alcohol screen.

- A positive test for HIV antibody.

- Pregnant females as determined by positive hCG test at screening or prior to dosing.

- Where participation in the study would result in donation of blood or blood products
in excess of 500mL within a 56 day period.

- Lactating females.

- 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).

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day.

- Unable to refrain from the 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.

- Unwillingness or inability to follow the procedures outlines in the protocol.

- Subject is mentally or legally incapacitated.

- Consumption of grapefruit or grapefruit juice within 7 days prior to the first dose
of study medication.