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

NCT ID: NCT00612456

Last Updated: 2017-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-05
• Study Completion Date: 2009-06-17

Brief Summary

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

Detailed Description

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.

Conditions

Macular Degeneration

Keywords

angiogenesis; pazopanib,; age-related macular degeneration (AMD),; vascular endothelial growth factor (VEGF),; choroidal neovascularization (CNV),

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm 1

Pazopanib eye drops formulation 5 mg/mL daily for 28 days

Group Type: EXPERIMENTAL

Pazopanib

Intervention Type: DRUG

Pazopanib eye drops formulation

Arm 2

Pazopanib eye drop formulation 5mg/mL TID for 28 days

Group Type: EXPERIMENTAL

Pazopanib

Intervention Type: DRUG

Pazopanib eye drops formulation

Arm 3

Pazopanib eye drop formulation 2mg/mL TID for 28 days

Group Type: EXPERIMENTAL

Pazopanib

Intervention Type: DRUG

Pazopanib eye drops formulation

Interventions

Pazopanib

Pazopanib eye drops formulation

Intervention Type: DRUG

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Tucson, Arizona, United States

GSK Investigational Site

Beverly Hills, California, United States

GSK Investigational Site

Pasadena, California, United States

GSK Investigational Site

Sacramento, California, United States

GSK Investigational Site

Fort Lauderdale, Florida, United States

GSK Investigational Site

Winter Haven, Florida, United States

GSK Investigational Site

Indianapolis, Indiana, United States

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Ann Arbor, Michigan, United States

GSK Investigational Site

Grand Rapids, Michigan, United States

GSK Investigational Site

Toms River, New Jersey, United States

GSK Investigational Site

Winston-Salem, North Carolina, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Austin, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Salt Lake City, Utah, United States

GSK Investigational Site

Sydney, New South Wales, Australia

GSK Investigational Site

Sydney, New South Wales, Australia

GSK Investigational Site

Melbourne, Victoria, Australia

GSK Investigational Site

Perth, Western Australia, Australia

GSK Investigational Site

Leuven, , Belgium

GSK Investigational Site

Trieste, Friuli Venezia Giulia, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Turin, Piedmont, Italy

GSK Investigational Site

Florence, Tuscany, Italy

GSK Investigational Site

Padua, Veneto, Italy

Countries

United States; Australia; Belgium; Italy

Other Identifiers

MD7108240

Identifier Type: -

Identifier Source: org_study_id