A First Time in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2798745 in Healthy Subjects and Stable Heart Failure Patients

Inclusion Criteria

For Healthy Subject Cohorts (1-3):

• Male or female 18-75 years of age inclusive, at the time of signing the informed consent.
• Healthy as determined by a responsible and experienced physician, based on an evaluation including medical history, physical examination, laboratory tests and cardiac evaluation including ECG and echocardiogram. 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.
• Body weight >=50 kilogram (kg) and Body Mass Index (BMI) within the range 18-32 kilogram/ square meter (kg/m^2) (inclusive).
• 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 for this definition, "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 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 40mIU/mL and estradiol =50kg and BMI within the range 18-40kg/m^2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria

• 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 acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 6 months.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (approximately 240mL) of beer, 1 glass (125mL) of wine or 1 (25mL) measure of 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 and/or GSK Medical Monitor, contraindicates their participation.
• History of seizure disorder and or stroke within the last 5 years.
• Active ulcer disease or gastrointestinal (GI) bleeding.
• Current smokers (Cohorts 1-4 only).
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• A positive pre-study drug/alcohol screen.
• A positive test for human immunodeficiency virus (HIV) antibody.
• A screening cardiac Troponin (cTn) level >ULN.
• Baseline presence of severe aortic stenosis.
• 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.
• Left ventricular ejection fraction 160 millimeters of mercury [mmHg] or resting diastolic BP > 100 mmHg).
• Resting hypoxia while breathing room air (Peripheral capillary oxygen saturation [SpO2] 160 mmHg or reporting DBP >100 mmHg).
• Resting hypoxia while breathing room air (SpO2 <88 percent).