A decision to stop the study was made by the site and GSK project team based on pre-defined stopping criteria in the protocol

This first time in human (FTIH) study assesses the safety, tolerability, and pharmacokinetics (PK) of single and multiple increasing doses of GSK2556286. It also includes food effect cohorts to evaluate how food influences the PK of GSK2556286. The findings will help determine appropriate dosing for future clinical studies.

Inclusion criteria:

• Participant must be 18 to 60 years of age inclusive, at the time of signing the informed consent. Participants aged 51 to 60 years must have received at least one dose of Coronavirus disease-2019 (COVID-19) vaccine approved by the local regulatory authority at least 3 weeks prior to signing the consent form.
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the normal reference range for the population being studied may be included only if the Investigator considers and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Body weight more than or equal to (>=)50 kilograms (kg) and body mass index (BMI) within the range 19 to 29.9 kilograms per meter square (kg/m^2) inclusive.
• Male and/or Female Participants. A male participant with a female partner of reproductive potential must agree to use contraception of this clinical study protocol during the treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. A female participant is eligible to participate if she is not a woman of childbearing potential (WONCBP).
• The participant is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

Exclusion criteria:

• Significant history of or current, cardiovascular, respiratory (including asthma), hepatic, renal, gastrointestinal, endocrine, hematological, infectious or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs: constituting a risk when taking part in the study or interfering with the interpretation of data.

• Alanine aminotransferase (ALT) greater than (>)1.5 times upper limit of normal (ULN).

• Total bilirubin >1.5 times ULN (isolated total bilirubin >1.5 times ULN may be acceptable, after consultation with the GlaxoSmithKline (GSK) Medical Monitor, if total bilirubin is fractionated and direct bilirubin less than [<]35 percent [%]).

• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or cholecystectomy.

• Current or past history of significant renal disease including renal stones.

• Current or past history of gastroduodenal ulcers or persistent gastritis requiring medication.

• Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.

• Exclusion criteria for screening electrocardiogram (ECG) with:

  1. Heart rate of <40 or >100 beats per minute (bpm) in males and <50 or >100 bpm in females.
  2. PR interval of <120 or >220 milliseconds (msec) in males and females.
  3. QRS duration of <70 or >120 msec in males and females.
  4. Electrocardiogram QT interval corrected for heart rate using Fridericia's formula (QTcF) interval of >450 msec in males and females.

• Evidence of previous myocardial infarction (does not include ST segment changes associated with re-polarization).

• Any clinically significant conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular [AV] block [second degree or higher], Wolff -Parkinson-White [WPW] syndrome).

• Sinus Pauses >3 seconds.

• Any significant arrhythmia which, in the opinion of the Investigator or GSK Medical monitor, will interfere with the safety for the individual participant.

• Non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic beats).

• Evidence of latent tuberculosis documented by:

  1. medical history and examination.
  2. Tuberculosis (TB) testing : either a positive tuberculin skin test (TST) (defined as a skin induration >5 millimeters [mm] at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) TB test such as QuantiFERON-TB Gold Plus test. In cases where the QuantiFERON or TST is indeterminate, the participant may have the test repeated once, but they will not be eligible for the study unless the second test is negative. In cases where the QuantiFERON or TST test is positive, the participant should be followed up as per standard of care.

• Use of prescription or non-prescription drugs, including Nonsteroidal anti-inflammatory drugs (NSAIDs), high-dose vitamins, herbal and dietary supplements (including St John's Wort) 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.

• Cotinine in urine indicative of smoking or history or regular use of tobacco or nicotine-containing products within 3 months.

• Current regular alcohol consumption defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 milliliters [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) 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 or Medical Monitor, contraindicates their participation.

• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.

• A positive test for Human immunodeficiency virus (HIV) antibody.

• Urinary analysis indicating presence of blood, protein or glucose. If trace or 1 plus (+) is found on urine dipstick, a repeat test can be performed. If repeat is positive, participant is excluded from recruitment.

• Screening age-appropriate estimated glomerular filtration rate (eGFR) <90 milliliters per minute mL/min as assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

• Serum (and in the MAD, urinary) electrolytes outside of normal range. May be repeated once if abnormal.

• A positive pre-study drug/alcohol screen.

• The participant has taken part 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: 90 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.

• Part A (Food Effect) Cohort: Participant must have no relevant dietary restrictions (lactose intolerance) or inability to eat a high fat meal.

IPD for this study will be made available via the Clinical Study Data Request site.

IPD will be made available within 6 months of publishing the results of the primary endpoints of the study, a key secondary endpoints and safety data of the study.

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

This is a double-blind study.