A Two-part Study to Investigate the Interaction and Pharmacokinetics of GSK2586184

Inclusion criteria

• Males and females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent. (Females are only eligible for Cohort A).
• 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 parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator in consultation with 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. Subjects with Hemoglobin (Hgb), Hematocrit (HCT), White blood cells (WBC), neutrophil or platelet values outside the normal range should always be excluded from enrolment.
• Body Mass Index (BMI) within the range 18 - 30 Kilogram per meter square (kg/m^2) (inclusive).
• For Cohort A 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, tubal occlusion procedure followed by a hysterosalpingogram that confirmed bilateral tubal occlusion, bilateral salpingectomy or hysterectomy [ "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 milli-international units per milliliter mIU/mL and estradiol < 40 picogram/milliliter (pg/mL) (<147 picomole/liter is confirmatory].
• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods: Condom plus partner use of a highly effective contraceptive or abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject. This criterion must be followed from the time of the first dose of study medication and for at least 2 weeks after their last dose.
• Normal creatinine clearance values at screening (calculated from serum creatinine by a predicting equation using Cockcroft-Gault formula), normal serum creatinine value as defined by the local reference laboratory, normal urine microscopy and no significant proteinuria on dipstick testing.
• Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <= 1.5 x Upper Limit of Normal [ULN] (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35 %).
• Based on averaged QT duration corrected for heart rate by Fridericia's formula (QTcF) values of triplicate ECGs obtained over a brief recording period: QTcF < 450 millisecond (msec); or QTcF < 480 msec in subjects with Bundle Branch Block.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion criteria

• A subject will not be eligible for inclusion in this study if any of the following criteria apply:

Criteria Based Upon Medical Histories

• 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.
• 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.
• Subjects who have taken statins and/or other Organic Anion-Transporting Polypeptide (OATP) and Breast Cancer Resistance Protein (BCRP) sensitive substrates (e.g. rapaglinide) in the 4 weeks prior to screening.
• A live vaccination within 4 weeks before the first dose of study medication, or a live vaccination planned during the course of the study (until completion of the follow-up visit).
• For Cohort A only: Any subject who has received an allogeneic bone marrow transplant must be excluded.

Criteria Based Upon Diagnostic Assessments

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• A positive pre-study drug/alcohol screen.
• Glycosylated Haemoglobin (HbA1c) result > 6.5 % (or 48 mmol/mol)
• A positive test for human immunodeficiency virus (HIV) antibody.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• 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.