The purpose of this study is to test the effects of study drug (GSK1605786) on the blood levels of multiple commonly used drugs that are given to measure how your liver breaks down the study drug. These commonly-used drugs are midazolam, pioglitazone, omeprazole, and rosuvastatin which will determine the effect of GSK1605786 on how the body breaks down (metabolizes) these commonly-used drugs. Blood samples for pharmacokinetic analysis of GSK1605786, and two metabolites, [GSK2635622 (CCX062) and GSK2656694 (CCX304)] and four probe substrates will be collected over a 24-hour period after administration. Safety will be assessed by the measurement of vital signs, cardiac monitoring, collection of adverse event assessments and laboratory tests.

Inclusion Criteria:

• Aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin less than or equal to 1.5x the upper limit of normal (isolated bilirubin >1.5x the upper limit of normal is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• 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 in the opinion of the Investigator the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Male or female between 18 and 55 years of age 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 (<147 pmol/L) is confirmatory].
• Body weight more than or equal to 60 kg and BMI within the range 19 - 30 kg/m2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form (including participation in pharmacogenetics research).
• QTc < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

Exclusion Criteria:

• A positive pre-study Hepatitis B surface antigen or Hepatitis B core antibody or positive Hepatitis C antibody result within 3 months of screening
• Current illness or disability that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study (e.g., an unstable cardiovascular, autoimmune, renal, hepatic, pulmonary, endocrine, metabolic, gastrointestinal, haematologic, or neurological condition or mental impairment)
• Current or pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic or renal function, that could interfere with the absorption, metabolism, or excretion of the study drugs; including but not limited to liver disease and 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 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 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, 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.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort [Hypericum perforatum], kava, ephedra [ma huang], gingko biloba, DHEA, vohimbe, saw palmetto, panaz ginseng, red yeast rice) 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 and through the duration of the study, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. Herbal medications include, but are not limited to: traditional Chinese, Korean and Japanese medicines, Panaz ginseng, Gingko biloba or St John's wort (Hypericum perforatum) or any Traditional Chinese herbal medicines (TCM) South Asian Ayurvedic medicine, Traditional Korean Medicines and Japanese Kampo.
• Use of aspirin, aspirin-containing compounds, salicylates or nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours of the first dose and is unwilling to abstain from use of these medications until the last pharmacokinetic sample has been collected.
• Use of liquid antacids (e.g. Maalox, Mylanta, Amphogel, milk of magnesia) or tablets (including chewable) antacids (e.g. TUMS™) within 48 hours of the first dose and is unwilling to abstain from use of these medications until the last dose of study medication.
• Use of digoxin or related cardiac glycoside (e.g digitoxin, deslanoside, lanatoside C, metildigoxin) within 7 days prior to screening and throughout 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.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• 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.
• Subject is mentally or legally incapacitated.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. This includes chewing tobacco, Gutka, hand-rolled tobacco cigarettes, Biddis, cigars, and Snuff.
• Use of caffeine- or theobromine-containing beverages (e.g., coffee, tea, certain colas, green tea and oolong tea, Yerba Mate, Guarana, and South American cocoa) and foods (e.g., chocolate), or alcohol-containing beverages within 72 hours prior to dosing
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice, pummelos, exotic citrus fruits, grapefruit hybrids, fruit juice blends, apple or orange juice, vegetables from the mustard green family [e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard] and charbroiled meats from 7 days prior to the first dose of study medication.
• Confirmed diagnosis of coeliac disease, those who follow a gluten-free diet to manage symptoms of suspected coeliac disease and subjects with a positive serologic test for tissue Transglutaminase, tTG (to screen for undiagnosed coeliac disease).
• Active or latent tuberculosis (TB) infection: All subjects will be tested with TB skin test (Mantoux test) and those with positive test result will be excluded.