A Safety Study in Healthy Volunteers to Evaluate Safety, How Fast the Drug is Absorbed, and the Side Effects of the Drug in Humans

The purpose of this study is to characterize more fully the safety, tolerability and
pharmacokinetics of single and repeat oral doses of pazopanib at lower doses than those
previously studied. The first part of the study is designed as an open-label, non-randomized,
single session, parallel-group, sequential dose-rising to investigate pharmacokinetics of
single oral doses in healthy adult subjects. In the second part of the study, healthy elderly
subjects will participate in one 14 day repeat-dose session, randomized to receive either
pazopanib or placebo. Dose escalation within Part 2, is based upon emerging safety and PK
data from each preceding repeat dosing cohort from at least 7 days of safety data as well as
emerging safety and PK data from single dose. The elderly population chosen for the second
part of the study will more closely reflect the target population for the AMD indication. The
results from the current study will assist in the dose selection of the subsequently planned
study in patients with AMD.

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 the first part of the study male or female greater than or equal to 18 years of
age and for the second part male or female greater than or equal to 50 years of age at
the time of signing the informed consent.

- A female subject is eligible to participate if she is of non-childbearing potential
defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or
postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases a
blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and
estradiol < 40 pg/ml (<140 pmol/L) or values consistent with local laboratory
recommended value is confirmatory.

- Body weight greater than or equal to 50 kg for men and greater than or equal to 45 kg
for women within the BMI range 19-30 kg/m2 (inclusive).

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

- Single QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

- Best-corrected visual acuity better than 20/80 (Snellen equivalent) in both eyes in
Part 2 only.

Exclusion Criteria:

- History of clinically relevant impaired endocrine, thyroid, hepatic, respiratory or
renal function, uncontrolled hypertension, diabetes mellitus, coronary heart disease,
or psychotic mental illness.

- History of any clotting disorder, including predisposition to hypercoagulation or any
previous thromboembolic event.

- Elevations in blood pressure, based on criteria provided in Section 7.2.3. OR Subjects
with a blood pressure >140/90 mmHg, at screening.

- 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.

- History of regular alcohol consumption within 6 months of the study defined as: For US
sites: an average weekly intake of >14 drinks for males or >7 drinks for females. One
drink is equivalent to 12 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.

- 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).

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day.

- Use of prohibited medications as described in Section 9.2.

- 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.

- Unwillingness or inability to follow the procedures outlined in the protocol.

- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
nicotine-containing products within 6 months prior to screening.

- Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days
prior to the first dose of study medication.

- Any prior intraocular surgery, excluding cataract surgery (Part 2 only)

- Any prior eye surgery within three months to first dose of study medication (Part 2
only).