GW824575 First Time in Human

Inclusion Criteria:

• AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. 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 GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• For subjects in Parts A or D - Male subjects between 18 and 65 years of age inclusive, at the time of signing the informed consent.

For subjects in Part B - Male subjects greater than or equal to 50 years of age, at the time of signing the informed consent..

• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in protocol. This criterion must be followed from the time of the first dose of study medication until 4 months post-last dose.
• Body weight greater than or equal to 55 kg and BMI within the range 18 - 31 kg/m2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Average QTc < 450 msec.
• Normotensive, after having rested quietly in a supine position for at least 15 minutes, with a systolic blood pressure less than or equal to 120 mmHg and diastolic blood pressure less than or equal to 80mmHg and a heart rate less than or equal to 100 beats per minute. Subjects with "pre-hypertension" (systolic blood pressure 121-140 mmHg and diastolic blood pressure 81 to 99mmHg) must be cleared by the medical monitor.
• Willingness and ability to swallow multiple size 00 capsules as part of study participation.
• For subjects in Part B only - Best-corrected visual acuity better than 20/80 (Snellen equivalent; 54 or more ETDRS letters) in both eyes.

Exclusion Criteria:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A positive pre-study drug/alcohol screen.
• A positive test for HIV antibody.
• Significant infection within 4 weeks prior to the first dosing day.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of greater than 21 units for males. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
• 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: 3 months (12 weeks), 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.
• Unable to refrain from 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 and throughout the study, 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 that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Any prior intraocular surgery, excluding cataract surgery.
• Any prior eye surgery within three months to first dose of study medication.
• Subjects with glaucoma (controlled or uncontrolled).
• Inability to withhold contact lens wear from the time of the screening ophthalmic assessments until the treatment ophthalmic assessments have been performed (the wearing of glasses is permitted).
• Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoxamine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol).