A Phase I Rheumatoid Arthritis Study in Healthy Volunteers

Inclusion Criteria:

• Healthy adult men or women as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests and cardiac assessment.
• Female subjects of non-childbearing potential.
• Male subjects must agree to abstain from or agree to use adequate contraception, in addition to having their female partner use another form of contraception. This criterion must be followed from the time of the first dose of study medication until Pharmacokinetic levels are determined to be below the LLQ.
• Men or women who are between 18 and 55 years of age, inclusive.
• Body Mass Index (BMI) within the range of 18-35 kilogram per meter square (kg/m^2) inclusive.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Exclusion Criteria:

• The subject has a positive pre-study urine drug/urine alcohol screen. A minimum list of drugs that will be screened for includes amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
• A history of regular alcohol consumption averaging >7 drinks/week for females or >14 drinks/week for males. One drink is equivalent to (12 g alcohol) = 5 ounces [150 milliliter (mL)] of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits
• The subject is unwilling to abstain from alcohol consumption from 48 hour prior to dosing until discharge from the clinic, and for 48 hour prior to all other out-patient clinic visits.
• Smoked or used tobacco or nicotine-containing products within the previous 6 months prior to the first dose of current study medication.
• The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
• Previous exposure to or treatment with PEGylated molecules.
• Use of anti-Tumor Necrosis Factor (anti-TNF) drugs within 60 days prior to dosing.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days , or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy (including antibiotics) which, in the opinion of the investigator and/or GSK Medical Monitor, contraindicates the subject's participation.
• Positive pregnancy test at Screening or on Day -1 (females only).
• Any clinically significant abnormality identified on the screening medical assessment or examination, or ECG.
• Any white blood cell (WBC) or neutrophil count outside the normal range at screening or on Day -1.
• History of significant cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions that in the opinion of the investigator and/or GSK Medical Monitor, places the subject at an unacceptable risk as participant in this trial.
• History of any autoimmune or current inflammatory conditions including rheumatoid arthritis or any other joint disease.
• History of malignancy, except for surgically cured basal cell carcinoma or cured cervical carcinoma (> 2 yrs prior to dosing).
• Currently has asthma or history of chronic obstructive pulmonary disease (COPD).
• Current evidence of ongoing or acute infection.
• The subject has a history of repeated, chronic or opportunistic infections which, in the opinion of the investigator and/or GSK Medical Monitor, places the subject at an unacceptable risk as a participant in this trial.
• History of Mycobacterium tuberculosis or any other previous Mycobacterium infection.
• A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody, or human immunodeficiency virus (HIV) antibody testing result.
• History of a severe allergic reaction, angio-edema, anaphylaxis or immunodeficiency
• History of elevated blood pressure or blood pressure >140/90 millimeters of mercury (mmHg) at screening.
• Corrected QT interval (QTc) > 450 milliseconds.
• Where participation in study would result in donation of blood in excess of 500 mL within 56 days of starting the study.
• Subject whose calculated creatinine clearance is less than 80 mL/min
• Liver function tests above the upper limit of normal at screening (alkaline transaminase (ALT), aspartate transaminase (AST) or bilirubin).
• Chronic liver or biliary disease, history of Gilbert's syndrome in a previous clinical study or at screening.