Inclusion Criteria:
- Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and
ECGs. A subject with a clinical abnormality or laboratory parameters outside the
reference range may be included only if the Investigator and GSK medical monitor
agree that the abnormality will not introduce additional risk factors and will not
interfere with the study procedures.
- Male or female between 18 and 55 years of age inclusive, at the time of signing the
informed consent.
- A female subject is eligible to participate if she is of non-childbearing potential
or of child-bearing potential if has a negative urine pregnancy test at screening and
Day - 1, and agrees to use agreed upon contraception methods until 56 days after
stopping study drug.
- Body weight >=60 kg (132 pounds) and BMI within the range 19-32 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form
Exclusion Criteria:
- A positive urine drug/alcohol screen at screening or Day -1.
- History or regular use of tobacco- or nicotine-containing products within 3 months
prior to screening.
- History of illicit drug abuse within 6 months prior to screening.
- History of regular alcohol consumption within 6 months of the study
- Subjects who are unwilling to comply with the lifestyle guidelines required.
- 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).
- Use of prescription or non-prescription drugs, including 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.
- History of sensitivity to any of the study medications or their components.
- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.
- Pregnant females as determined by positive urine hCG test at screening or prior to
dosing.
- Lactating females.
- Subject is mentally or legally incapacitated.
- A positive HIV antibody, Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.
- The subject's systolic blood pressure is outside the range of 90-150mmHg or diastolic
blood pressure is outside the range of 45-90mmHg or heart rate is outside the range
of 50-100bpm for female subjects and 45-100bpm for male subjects at screening and Day
- 1.
- Cardiac conduction abnormalities as specified inprotocol
- Any significant arrhythmia which, in the opinion of the principal investigator and
GSK medical monitor, will interfere with the safety for the individual subject.
- History of angina, ischemic heart disease, myocardial infarction, or clinically
significant arrhythmia.
- History of epilepsy, convulsions or psychological disorders.
- History of porphyria.
- AST, ALT or alkaline phosphatase >1. 5 times the upper limit of normal and/or total
bilirubin level outside the normal range at screening. A single repeat is allowed
for eligibility determination.
- Documented Glucose-6-phosphate dehydrogenase (G6PD) deficiency, determined by a
quantitative assay of enzyme activity.
- History of hemoglobinopathy; or current or past history of methemoglobinemia or
methemoglobin percentage above the reference range at screening.
- History of previous eye surgery involving the retina, Lasik surgery within 90 days,
or retinal/corneal abnormalities.
- Any clinically significant abnormalities on the screening Humphrey 10-2 visual field
test.
- Best corrected visual acuity worse than 0. 3 logMAR (20/40 Snellen equivalent) (i. e.,
20/40 or better vision will be allowed on study).
