To Evaluate the Pharmacodynamics, Safety, and Pharmacokinetics of Pazopanib Drops in Adult Subjects With Neovascular AMD
Condition: Macular Degeneration
MeSH terms: Macular Degeneration
Intervention: Pazopanib
Intervention description: Pazopanib eye drops formulation
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 70.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: angiogenesis; pazopanib,; age-related macular degeneration (AMD),; vascular endothelial growth factor (VEGF),; choroidal neovascularization (CNV),

Summary:

      This is a 28 day study to evaluate the pharmacodynamic effect of pazopanib eye drops on the
      central retinal thickness of AMD patients
    

Eligibility criteria:

        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