A Phase I Study to Assess the Pharmacokinetics of GSK2798745 Tablets

GSK2798745 is being developed as a novel therapeutic intervention for the treatment of pulmonary edema associated with heart failure (HF) and is currently under investigation in the form of a compounded capsule. This is an open-label, randomized, single-dose, crossover study with the purpose to determine the pharmacokinetics (PK) of three 2.4 milligrams (mg) tablet formulations of GSK2798745 in 12 healthy subjects. The three formulations developed for this study will be micronized GSK2798745 active pharmaceutical ingredient (API) (Tablet A), micronized GSK2798745 API with sodium lauryl sulfate (SLS) and hypromellose (Tablet B), milled GSK2798745 API with SLS and hypermellose (Tablet C), and Tablet D, which will be either A/B/C based on interim PK analysis of data from the first three treatment periods.

Following a 30-day screening period, subjects will be randomized to one of the 6 treatment sequences: Treatment sequence 1: ABCD, 2=CABD, 3=ACBD, 4=BACD, 5=BCAD, 6=CBAD over three 4-day treatment periods. For treatment period 4, the best formulation based on the interim analysis data from the three treatment periods will be evaluated under fed conditions. Each treatment period will be separated by a minimum of 7 (+14)-day washout period. The total duration of participation in the study will be approximately 11 weeks including the follow-up visit.


Eligibility Criteria:
Inclusion Criteria:

* Between 18 and 75 years of age inclusive, at the time of signing the informed consent
* Healthy as determined by the investigator or medically qualified designee 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 Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
* Body weight \>=50 kg and body mass index within the range 18 - 32 kilogram (kg)/meter (m)\^2 (inclusive)
* Male or female of non-child bearing potential:

A male subject with a female partner of child bearing potential is eligible to participate if he agrees to use contraception as mentioned in the protocol during the treatment period and for at least 7 days after the last dose of study treatment and refrain from donating sperm during this period A female subject is eligible to participate if she is not a woman of childbearing potential (WOCBP) as defined in the protocol.

* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol

Exclusion Criteria:

* History of acute coronary syndromes including unstable angina or myocardial infarction within 6 months of screening
* History of stroke or seizure disorder within 5 years of Screening
* Active ulcer disease or gastrointestinal bleeding at the time of screening
* Alanine transaminase (ALT) and bilirubin \>1.5x Upper limit of normal (ULN) is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
* QT interval corrected according to Fridericia's formula (QTcF) \>450 milliseconds (msec)
* History or current evidence of any serious or clinically significant gastrointestinal, renal, endocrine, neurologic, hematologic or other condition that is uncontrolled on permitted therapies or that would, in the opinion of the investigator or the Medical Monitor, make the subject unsuitable for inclusion in this study
* Urinary cotinine levels indicative of current smoking or regular use of tobacco- or nicotine-containing products at time of screening (cotinine levels \>200 nanogram \[ng\]/millimeter \[mL\])
* History of alcohol abuse within 6 months of the study based on the following criteria:

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 Medical Monitor, contraindicates their participation
* Presence of hepatitis B surface antigen, positive hepatitis C antibody test result at screening or within 3 months of screening.
* A positive test for human immunodeficiency virus antibody
* A positive pre-study drug/alcohol screen
* A screening cardiac Troponin level \> ULN
* Use of another investigational product in a clinical study within the following time period prior to the first administration of study medication 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 4 investigational medicinal products within 12 months prior to the first administration of study medication.
* Unable to refrain from the use of prescription or non-prescription drugs (including vitamins and dietary or herbal supplements) except permitted medications listed in the protocol, 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 until completion of the follow-up visit, unless in the opinion of the Investigator and/ or sponsor the medication will not interfere with the study.