Study to Evaluate the Pharmacokinetics and Safety of GSK2336805 in Subjects With Hepatic Impairment and Healthy Matched Control Subjects

• Male and female subjects aged 18 to 74 years inclusive, at the time of signing the informed consent.
• Body weight >=45 kilogram (kg) for men and women and body mass index (BMI) within the range 17- 41 kg/meter square (m\^2) for hepatically impaired subjects; healthy matched control subjects will be matched to BMI +/- 20% and must also remain in the BMI range of 17- 41 kg/m\^2.
• A female subject is eligible to participate if she is of non-childbearing potential (postmenopausal defined as 12 months of spontaneous amenorrhea or pre-menopausal females with a documented tubal ligation or hysterectomy).
• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until the follow up visit.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned.
• Ability and willingness to abstain from alcohol-containing beverages/foods from 48 hours prior to entry in the clinical study centre until discharge.
• Supplemental inclusion criteria for Healthy Volunteer subjects only: A male or female is eligible for study participation if he/she is healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and electrocardiogram (ECG), including no cardiac, pulmonary, hepatic, biliary, gastrointestinal, or renal disorders (defined as serum creatinine >1.5 milligram(mg)/decilitre (dL) or a calculated creatinine clearance (CrCl)\<50 millilitre (mL)/ minute(min), or cancer within the past 5 years (except localized or in situ cancer of the skin). 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 and the Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. A single repeat laboratory evaluation is allowed for eligibility determination. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and bilirubin less than the upper limits of normal. The subject's systolic blood pressure is inside the range of 90-140 millimeter of mercury (mmHg) and diastolic blood pressure is inside the range of 45-90 mmHg and heart rate is inside the range of 50-100 beats per minute (bpm) for female subjects or 45-100 bpm for male subjects.
• Supplemental inclusion criteria for all hepatically impaired subjects: Chronic (>6 months), stable (no acute episodes of illness within the previous 1 month prior to screening due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology. Subjects must also remain stable throughout the Screening period.
• Subjects whose platelets are greater than or equal to 30,000 x 10\^9/Liter of blood who have not had any major bleeding episodes within the past 6 months.
• Supplemental inclusion criteria for all hepatically impaired subjects in the mild group: A male or female is eligible for study participation if he/she is considered to have mild hepatic insufficiency (of any etiology) and has been clinically stable for at least 1 month prior to screening. To be classified as having mild hepatic insufficiency, subjects must have: A Child-Pugh score of 5-6 with known medical history of liver disease (with or without a known history of alcohol abuse) and previous confirmation of liver cirrhosis by liver biopsy or other medical imaging technique (including laparoscopy, computed tomography [CT] scan, Magnetic Resonance Imaging [MRI] or ultrasonography) associated with an unambiguous medical history.
• Supplemental inclusion criteria for all hepatically impaired subjects in the moderate group: A male or female is eligible for study participation if he/she is considered to have moderate hepatic insufficiency (of any etiology) and has been clinically stable for at least 1 month prior to screening. To be classified as having moderate hepatic insufficiency, subjects must have: A Child-Pugh score of 7-9 with known medical history of liver disease (with or without a known history of alcohol abuse) and previous confirmation of liver cirrhosis by liver biopsy or other medical imaging technique (including laparoscopy, CT scan, MRI or ultrasonography) associated with an unambiguous medical history.
• Supplemental inclusion criteria for all hepatically impaired subjects in the severe group: A male or female is eligible for study participation if he/she is considered to have severe hepatic insufficiency (of any etiology) and has been clinically stable for at least 1 month prior to screening. To be classified as having severe hepatic insufficiency, subjects must have: A Child-Pugh score of >9 with known medical history of liver disease (with or without a known history of alcohol abuse) and previous confirmation of liver cirrhosis by liver biopsy or other medical imaging technique (including laparoscopy, CT scan, MRI or ultrasonography) associated with an unambiguous medical history

Exclusion Criteria:

• Pregnant females as determined by positive serum or urine Human Chorionic Gonadotropin (hCG) test at screening or prior to dosing.
• Lactating females.
• 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 (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.
• A positive test for human immunodeficiency virus (HIV) antibody.
• Where 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).
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice, pummelos, satsuma, ugli, tangerine, and tangelo, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
• Use of prescription or non-prescription drugs, vitamins, and 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. Hepatically impaired subjects requiring prescription or non-prescription drugs may be acceptable provided the medications are not on the Prohibited Medications List of the protocol and in the opinion of the Investigator the medication will not interfere with the study procedures or compromise subject safety.
• History or presence of allergy or intolerance to the study drugs or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. In addition, if heparin is used during pharmacokinetic (PK) sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
• The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines. For hepatically impaired subjects, a positive drug screen will be allowed if it is due to a prescribed medication, provided that medication is not on the Prohibited Medications List of the protocol.
• Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart rate \<45 and >100 beats per minute (bpm) (males) and \<50 and >100 bpm (females); PR Interval \<120 and >220 milliseconds (msec); QRS duration \<70 and >120 msec; corrected QT interval by Bazett's formula (QTcB) >450 msec or >480 msec in subjects with incomplete Bundle Branch Block; Evidence of previous ischemic, valvular, or congenital heart disease (Does not include ST segment changes associated with repolarization); Any clinically significant 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; Any significant arrhythmia which, in the opinion of the principal investigator, will interfere with the safety for the individual subject; and Non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats).
• Supplemental exclusion criteria for healthy volunteer subjects only: A positive Hepatitis B surface antigen or positive Hepatitis C antibody result at screening. Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of inflammatory bowel disease should be excluded. Subjects with a history of peptic ulceration or pancreatitis within the preceding 6 months of screening should be excluded. Subjects with any previous gastrointestinal (GI) surgery (except appendectomy or gall bladder removal more than three months prior to study) may be enrolled in this study only if, in the opinion of the Investigator and the Medical Monitor, it is not expected to interfere with the study procedures or to pose an additional safety risk to the subject. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Supplemental exclusion criteria for hepatically impaired subjects only:
• Evidence of recent, acute infection with Hepatitis B and/or Hepatitis C within preceding 6 months. Subjects with chronic Hepatitis B or C (duration >6 months) are eligible for enrolment.
• Subjects with a pre-existing condition (except hepatic impairment) interfering with normal gastrointestinal anatomy or motility that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of inflammatory bowel disease should be excluded. Subjects with a history of peptic ulceration or pancreatitis within the preceding 6 months of screening should be excluded. Subjects with previous gastrointestinal (GI) surgery (except appendectomy or gall bladder removal more than three months prior to study) may be enrolled in this study only if, in the opinion of the Investigator and the Medical Monitor, it is not expected to interfere with the study procedures or to pose an additional safety risk to the subject.
• Subjects receiving lactulose who are medically unable to halt lactulose administration from 8 hour (h) before dosing with study drug to 4h after dosing with study drug.
• Subjects with severe encephalopathy (grade 3 or 4) as judged by the investigator or significant Central Nervous System (CNS) disease (e.g. dementia, or seizures) which the investigator considers will interfere with the informed consent, conduct, completion, or results of this trial or constitutes an unacceptable risk to the subject.
• Subjects with a change in dose regimen of medically required medication within the 2 weeks prior to dosing.
• Subjects with creatinine clearance \<=50 mL/min (calculated by the Cockcroft-Gault Formula). If the result calculated by Cockcroft-Gault is between 40 and 50 mL/min, then the site may complete a 24 hour urine collection to more specifically calculate the CrCl. A CrCl value \< or = 50mL/min via 24-hour urine collection is also exclusionary.
• History of gastric or esophageal variceal bleeding within the past 6 months and for which varices have not been adequately treated with medication and/or surgical procedures.
• Subjects with electrolyte imbalance whose serum sodium levels are less than or equal to 125 millimol/litre (mmol/L); potassium levels are less than or equal to 2.5 mmol/L; calcium levels less than or equal to 6.1mmol/L).
• Presence of hepatopulmonary or hepatorenal syndrome.
• Primarily cholestatic liver diseases.
• History of liver transplantation.
• Subjects in the severe hepatic impairment group that are expecting a liver transplant during the study participation period.
• Subjects with signs of active bacterial infection (including active spontaneous bacterial peritonitis).
• Subjects with Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement within the past 3 months.
• Subjects with unstable cardiac function or subjects with hypertension whose blood pressure that is not well controlled (based on the investigator's discretion)
• Diabetic subjects whose diabetes that is not controlled (based on the investigator's discretion).