A Study to Investigate the Pharmacokinetics (PK) of Modified Release (MR) Prototype Coated Tablet Formulations of GSK2982772

Previous clinical studies of immediate release (IR) formulations of GSK2982772 resulted in a high peak to trough ratio of GSK2982772. Additionally, the short half-life for GSK2982772 (approximately 2 to 3 hours) necessitates twice a daily (BID) or thrice daily (TID) dosing of an IR formulation. As a result, MR formulations using a polymer matrix approach with minitablets in capsule and MR tablet formulations were investigated. The emerging PK data of the MR formulations investigated to date have demonstrated that a once daily (QD) PK profile can be achieved in the fasted state but the polymer matrix formulation is susceptible to food effects when administered with a high fat breakfast. The purpose of this study is to evaluate MR prototype coated tablet formulations. This study will evaluate the PK of MR prototype coated tablet formulations of GSK2982772. The study is divided into two parts; Part A and Part B. The MR tablet coating used in Part A and the initial periods of Part B will have an aperture drilled into the enteric coating of either side of the tablet. This allows some drug release to commence in the stomach whilst providing controlled release throughout the gastrointestinal (GI) tract. In Part B only, a new investigational medicinal product (IMP) will be manufactured to allow comparison of the tablet coating either with apertures (i.e., drilled) or without apertures (i.e., full coat/non drilled). Part A will be a 6-period, 6-way fixed sequence design, up to 4 MR tablet prototype coated formulations will be evaluated in fasted state at 240 milligrams (mg). Periods 1, 2 and 3 will evaluate MR1, IR tablet and MR2 respectively. Periods 4, 5 and 6 will be flexible and the dosing regimen will be dependent on the outcome of Periods 1 to 3. In addition, the impact of food (high fat meal, standard breakfast or administration 30 or 60 minutes before a standard breakfast) on selected MR prototype coated tablet formulations may also be evaluated in Period 4, 5 or 6 of Part A. Each inpatient period for MR regimens (Periods 1, 3, 4 to 6) will consist of 4 days and 3 nights, and the inpatient period for the IR tablet (Period 2) will consist of 3 days and 2 nights. There will be a minimum washout of 7 days between doses, and a follow-up visit will occur at 7 to 9 days after the last study treatment. The Part B of the study will be a 7-period fixed sequence which will evaluate the selected MR prototype coated tablet formulation(s) at different tablet strengths or as multiple unit doses and with or without apertures in the tablet coatings. There will be an interim review after each period 1 to 5 of Part B to select the dose level, formulation and prandial status for each subsequent period. An interim data review after Part B Period 6 will determine if optional Period 7 is required and the dose level, dosing time (morning or evening), formulation and prandial status for that period. Each inpatient period will consist of a 4-day and 3-night with a minimum of 7 days washout between doses. A follow-up visit will occur at 7 to 9 days after the last study treatment. Approximately 33 subjects will be enrolled in the study. The total duration for Part A will be approximately 10-12 weeks and 10-14 weeks for Part B (including screening period of approximately 4 weeks).


Eligibility Criteria:
Inclusion Criteria:

* Subject at the time of participation must be 18 to 65 years of age.
* Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
* Body weight greater than or equal to 50 kilogram (kg) and body mass index within the range 19.0 to 32.0 kg per squared meter (kg/m\^2) (inclusive).
* Male or female subjects where male subjects are eligible to participate if they agree to the following during the intervention period until completion of the final follow up visit after the last dose of study treatment; refrain from sperm donation; plus either be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception/barrier like use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant; agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person.
* The eligible female subjects can participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP); is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of less than 1 percentage per year), preferably with low user dependency, for at least 30 days before first dose until completion of the final follow up visit after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction from Day 1 until 3 months after the last dose. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention; a WOCBP must have a negative highly sensitive serum pregnancy test within 24 hours before the first dose of study intervention; additional requirements for pregnancy testing during and after study intervention must be followed; the investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
* Capable of giving an Informed Consent.

Exclusion Criteria:

* History of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
* Any history of suicidal behavior within the past 6 months or any history of attempted suicide in subject's lifetime.
* History of clinically significant psychiatric disorders as judged by the investigator. Depression requiring treatment in the last 2 years.
* History of herpes zoster (shingles) reactivation.
* History or diagnosis of obstructive Sleep Apnea.
* History of a significant respiratory disorder. Childhood asthma that has fully resolved is permitted.
* History or current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
* A positive diagnostic tuberculosis (TB) test at screening defined as a positive QuantiFERON-TB Gold test or T-spot test. In cases where the QuantiFERON or T-spot test is indeterminate, the subject may have the test repeated once, but they will not be eligible for the study unless the second test is negative.
* History of GI surgery (with exception of appendectomy).
* History of cholecystectomy or gall stones.
* Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active.
* Alanine transaminase (ALT) greater than 1.5 times upper limit of normal (ULN).
* Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percentage of total).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome).
* Corrected QT interval (QTcF) greater than 450 milliseconds (msec).
* Past or intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing (paracetamol/acetaminophen \[up to 2 gram per day\], hormone replacement therapy and hormonal contraception are permitted).
* Live or attenuated vaccine(s) within 30 days of enrolment, or plans to receive such vaccines during the study or plans to receive a vaccine within 30 days plus 5 half lives, of the last dose of study medication.
* Participation in the study would result in loss of blood or blood products in excess of 500 mL within a 56 day period; therefore donation or loss of greater than 400 mL of blood within the previous 3 months.
* Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
* Current enrolment or past participation within the last 3 months before signing of consent in this or any other clinical study involving an investigational study treatment or any other type of medical research.
* Subjects who have previously been enrolled in this study. Subjects in Part A of this study are not permitted to participate in Part B.
* Current or history of renal disease or estimated glomerular filtration rate by chronic kidney disease epidemiology collaboration (CKD-EPI) equation calculation less than 60 milliliter (mL) per minute per 1.73 m\^2 at screening.
* Presence of Hepatitis B surface antigen (HBsAg) at screening. Positive Hepatitis C antibody test result at screening or within 3 months prior to first dose. As potential for and magnitude of immunosuppression with this compound is unknown, subjects with presence of Hepatitis B core antibody (HBcAb) should be excluded. Subjects positive for HBsAg and/or positive for anti-HBc antibody (regardless of anti-HBs antibody status) are excluded.
* An elevated C-reactive protein (CRP) outside the normal reference range.
* Confirmed positive pre-study drug/alcohol screen.
* Positive human immunodeficiency virus (HIV) antibody test.
* Regular use of known drugs of abuse, or history of drug or alcohol abuse in the past 5 years.
* Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of greater than 21 units for males or greater than14 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer or 1 (25 mL) measure of spirits, 1.5 to 2 units is 1 glass (125 mL) of wine, depending on type.
* Current use or history of regular use of tobacco- or nicotine-containing products within 6 months prior to screening. A carbon monoxide breath test reading of greater than 10 parts per million (ppm).
* Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
* Subjects who do not have suitable veins for multiple venipuncture's/cannulation as assessed by the investigator at screening.
* Total cholesterol greater than or equal to 300 mg per deciliter (mg/dL) (greater than or equal to 7.77 millimole per liter \[mmol\]/L\]) or triglycerides greater than or equal to 250 mg/dL (greater than or equal to 2.82 mmol/L).
* Subjects who are study site or sponsor employees, or immediate family members of a study site or sponsor employee.