Relative Bioavailability, Safety, Tolerability, Pharmacokinetics (PK) and Food Effect Study of GSK2140944 in Healthy Subjects

This study will be conducted in three parts (Part 1, Part 2 and Part 3). Part 1 of this study will evaluate the relative bioavailability of a single dose of GSK2140944 tablet formulation compared to the reference capsule formulation under fasted conditions. The effect of food on the pharmacokinetics (PK) of a single dose of the tablet formulation will also be assessed. Part 2 will evaluate the effect of repeat doses of itraconazole on the pharmacokinetics of GSK2140944 following a single dose. A decision will be made whether to use the current capsule formulation or the new tablet formulation in Part 2 based upon the safety and PK data obtained from Part 1. Part 3 is conditionally based upon progression of the tablet formulation from Part 1 and will evaluate the effect of food on the safety, tolerability, and pharmacokinetics of the tablet formulation following multiple doses in elderly healthy subjects.


Eligibility Criteria:
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 feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
* Part 1 and 2: Male or female between 18 and 64 years of age inclusive, at the time of signing the informed consent. Part 3: Male or female subjects at least 65 years of age or older 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. To confirm post-menopausal status, a blood sample for simultaneous follicle stimulating hormone (FSH) \>40 milli-International Units (MIU)/milliliter (mL) and estradiol \<40 picograms (pg)/mL (\<147 picomoles \[pmol\]/liter \[L\]) is confirmatory. Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods. This criterion must be followed from the time of the first dose of study medication until the final follow-up visit.
* Body weight \>=50 kilograms (kg) and body mass index (BMI) within the range 19 - 31 kg/meter square (m\^2) (inclusive).
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
* Alanine amino transferase (ALT), alkaline phosphatase and bilirubin \<=1.5xUpper Limit of Normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).

Exclusion Criteria:

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).
* Any clinically significant central nervous system (e.g., seizures), cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions or history of such conditions that, in the opinion of the investigator may place the subject at an unacceptable risk as a participant in this trial or may interfere with the absorption, distribution, metabolism or excretion of drugs.
* History of photosensitivity to quinolones.
* Use of systemic antibiotic within 30 days of screening
* Previous exposure to GSK2140944
* Confirmed history of C-difficile diarrhea.
* History of tendon rupture.
* History of drug abuse within 6 months of the study.
* History of smoking or use of nicotine containing products within 3 months of screening, or a positive urine cotinine indicative of smoking at screening.
* 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 grams 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.
* History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical research unit uses heparin to maintain intravenous cannula patency).

Criteria Based Upon Diagnostic Assessments

* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening or positive Human Immunodeficiency Virus (HIV) antibody.
* A screening or Day -1 urinalysis positive for protein or glucose (greater than 1+ findings of protein or glucose).
* A serum creatinine value that is increased by more than 0.2 milligram (mg)/deciliter (dL) (or 15.25 micromoles/L) between screening and Day -1.
* For Part 3 Only: Neutrophil count \<2000 cells/microliter (a single repeat is allowed for eligibility determination).
* A positive urine test for drugs of abuse or alcohol (or alcohol breath test) at screening or at Day -1.
* Exclusion criteria for screening and baseline ECG (a single repeat is allowed for eligibility determination) as follows: Heart rate: \<40 and \>100 beats per minute (bpm) for males and \<50 and \>100 bpm for females; PR Interval: \<120 and \>220 milliseconds (msec); QRS duration: \<70 and \>100 msec; QT duration corrected for heart rate by Bazett's formula (QTcB) or QT duration corrected for heart rate by Fridericia's formula (QTcF) interval\>450 msec. Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization). Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular (AV) block \[2nd degree or higher\], Wolf Parkinson White \[WPW\] syndrome), sinus pauses\> 3 seconds, non-sustained or sustained ventricular tachycardia (\>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual subject.

Other Criteria

* Donation of blood in excess of 500 mL within 12 weeks prior to dosing or 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.
* Unwillingness to commit to avoid excessive exposure to sunlight (or exposure to a tanning bed) which would cause a sunburn reaction from first dose up to and including the follow-up visit.