To Estimate the Potential Effects of Repeat Doses of Darapladib on the Pharmacokinetics (PK) of Rosuvastatin as Well as Evaluating Safety and Tolerability in Healthy Volunteers

This is an interventional treatment trial for Atherosclerosis focused on measuring Drug interaction, rosuvastatin, healthy volunteer, Lp-PLA2, atherosclerosis, darapladib, pharmacokinetics. Read More

Inclusion Criteria:

• 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 a clinical abnormality 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.
• Male or female between 20 and 64 years of age inclusive, at the time of signing the informed consent.
• Subject must be of Caucasian or of Far-East Asian Descent. Far -East Asian is defined as a person of self-reported Asian ancestry including that of Japanese, Korean or Chinese descent (which includes Taiwanese subjects) [for Part B only].
• Far East Asian subjects must have been born in their native countries and have resided less than 10 years outside their native countries [for Part B only].
• Far East Asian subjects must have maintained a lifestyle, including diet, without significant change since leaving his/her native country [for Part B only].
• 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 > 40 milliliter of urine (MlU)/ milliliter (mL) and estradiol < 40 picogram/mL (<147 picomoles/liter is confirmatory] or Child-bearing potential and is abstinent or agrees to use one of the 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 follow-up.
• Body mass index within the range 19 to 37 kilogram/meter^2 (inclusive)

Exclusion Criteria:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• A positive pre-study drug/alcohol screen.
• A positive test for human immune virus (HIV) antibody
• 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 gram 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: Thirty 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.
• 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.
• Where participation in a previous study or donor bank would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Requiring the use of oral or injectable strong cytochrom P3A4 inhibitors.
• Pregnant females as determined by positive human chorionic gonadotropin test at screening or prior to dosing.
• Lactating females.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.
• History of sensitivity to heparin or history of heparin-induced thrombocytopenia.
• History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions Clinical criteria for diagnosing anaphylaxis or severe allergic responses.
• Consumption of grapefruit or grapefruit juice >8 ounce within 7 days prior to the first dose of study medication