To Evaluate the Pharmacodynamics, Safety, and Pharmacokinetics of Pazopanib Drops in Adult Subjects With Neovascular AMD

Pazopanib has been formulated as an eye drop for the topical treatment of age-related macular
degeneration (AMD). Safety, tolerability and pharmacokinetics have been evaluated in a first
study conducted in healthy volunteers (MD7108238). In the present study, three dosing
regimens of pazopanib eye drops, administered for 28 days, will be evaluated in subjects with
occult or minimally classic subtypes of choroidal neovascularization due to AMD. This study
is designed to measure pharmacological activity of topically administered pazopanib in target
tissues (choroid and retina) of patients with AMD by weekly evaluation of central retinal
thickness as measured by optical coherence tomography (OCT). Evaluation of efficacy will be
performed on an exploratory basis by weekly measurement of visual acuity. The ocular and
systemic safety and systemic pharmacokinetics of pazopanib treatment for 28 days will also be
evaluated.

Inclusion Criteria:

- Age-related macular degeneration patients diagnosed with subfoveal choroidal
neovascularization in the study eye, with all of the following characteristics
required:

- central subfield thickness > 300 microns on investigator-determined OCT
(inclusive of subretinal fluid)

- active subfoveal leakage as determined by investigator-determined fluorescein
angiography

- minimally classic or occult with no classic CNV lesion

- lesion size no greater than 12 disc areas

- CNV > 50% of lesion area

- < 50% of lesion area with blood

- = 25% of lesion area with fibrosis

- Best-corrected ETDRS visual acuity in the study eye between 80 to 24 letters inclusive
(approximately 20/25 and 20/320 or 4/5 to 4/63) at screening

- Female subjects must be of non-childbearing potential.

Exclusion Criteria:

- Additional eye disease in the study eye that could compromise best corrected visual
acuity (i.e. glaucoma with documented visual field loss, clinically significant
diabetic retinopathy, ischemic optic neuropathy, or retinitis pigmentosa).

- CNV in the study eye due to other causes unrelated to age-related macular
degeneration.

- The presence of retinal angiomatous proliferation (RAP) in the study eye, as
determined by the investigator (confirmation by indocyanine green angiography is not
required).

- Geographic atrophy involving the center of the fovea in the study eye.

- Anterior segment and vitreous abnormalities in the study eye that would preclude
adequate observation of the fundus for photographs, fluorescein angiography and OCT.

- Vitreous, subretinal or retinal hemorrhage in the study eye that is unrelated to AMD.

- More than one prior photodynamic therapy (PDT) treatment in the study eye.

- PDT treatment in the study eye < 12 weeks prior to dosing.

- Previous treatment in the study eye with ranibizumab (Lucentis) or bevacizumab
(Avastin) without resolution of exudation (intraretinal and subretinal fluid as
documented by OCT).

- Use of any treatment, either approved or experimental, for AMD in the study eye within
60 days of first dose of investigational product.

- Intraocular surgery in the study eye within 3 months of dosing.

- Aphakia or total absence of the posterior capsule (Yttrium aluminum garnet (YAG)
capsulotomy permitted) in the study eye.

- History of vitrectomy in the study eye.

- Use of topical ocular medications in the study eye within 7 days of first dose of
investigational product or expected use of topical ocular medications during the
treatment period, with the exception of artificial tears (refer to Section 9.1)

- Active treatment in the fellow eye, with the exception of preservative-free artificial
tears.

- Current use of medications known to be toxic to the retina, lens or optic nerve (e.g.
desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines,
tamoxifen, nicotinic acid, and ethambutol).

- Use of systemic steroids (>10 mg prednisone or equivalent/day) within 14 days of first
dose.

- An unwillingness to refrain from wearing contact lenses starting from the screening
visit, through the follow-up visit

- Medical history or condition:

- Uncontrolled Diabetes Mellitus, with hemoglobin A1c (HbA1c) > 10%.

- Myocardial infarction or stroke within 12 months of screening.

- Active bleeding disorder.

- Major surgery within 1 month of screening.

- Hepatic impairment.

- Uncontrolled hypertension