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

NCT00612456 | Completed Phase 2 Results

• 1 other identifier: MD7108240
• Study Type: interventional
• Target: 70
• Locations: 4 countries
• Sites: 27

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

Conditions

Macular Degeneration

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in Central Retinal/Lesion Thickness (CRLT) as Measured by the Carl Zeiss Meditec Stratus Optical Coherence Tomography (OCT) Scanner at Day 29

  CRLT was measured by the Carl Zeiss Meditec Stratus OCT scanner based on the manual measurement of the distance between the inner and outer retina, inclusive of subretinal fluid and any choroidal neovascularization (CNV) as measured in the central 1 millimeter (mm) area of the 7 mm Posterior Pole Scan. OCT scans/images were collected by trained and certified photographer and analyzed by investigator. Two datasets were used for analysis namely Last observation carried forward (LOCF) which included missing assessment for a participant who completed at least 7 days of pazopanib eye drop replaced by the last non-missing assessment post 7 days of pazopanib eye drop treatment. OC dataset included a missing assessment at any scheduled time was considered unevaluable and was not imputed. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization value at Day 29.

  Baseline (Day -3 to -1) and Day 29

Secondary Outcomes (13)

• Number of Participants With Complete Ophthalmic Examination Values of Potential Clinical Concern

  Upto follow-up (Day 43)

• Number of Participants With Vital Sign Data for Systolic Blood Pressure and Diastolic Blood Pressure and Heart Rate of Potential Clinical Concern

  Up to follow up (Day 46)

• Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings

  Day 15 and follow-up (Day 43)

• Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern

  Up to follow-up Day 43

• Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis

  Day 29 and follow-up (Day 43)

Study Arms (3)

Arm 1

EXPERIMENTAL

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

Drug: Pazopanib

Arm 2

EXPERIMENTAL

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

Drug: Pazopanib

Arm 3

EXPERIMENTAL

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

Drug: Pazopanib

Interventions

Pazopanib DRUG

Pazopanib eye drops formulation

Arm 1; Arm 2; Arm 3

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (27)

GSK Investigational Site

Tucson, Arizona, 85704, United States

Location

GSK Investigational Site

Beverly Hills, California, 90211, United States

Location

GSK Investigational Site

Pasadena, California, 91105, United States

Location

GSK Investigational Site

Sacramento, California, 95841, United States

Location

GSK Investigational Site

Fort Lauderdale, Florida, 33334, United States

Location

GSK Investigational Site

Winter Haven, Florida, 33880, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46280, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02111, United States

Location

GSK Investigational Site

Ann Arbor, Michigan, 48105, United States

Location

GSK Investigational Site

Grand Rapids, Michigan, 49525, United States

Location

GSK Investigational Site

Toms River, New Jersey, 08755, United States

Location

GSK Investigational Site

Winston-Salem, North Carolina, 27157, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15213, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Salt Lake City, Utah, 84132, United States

Location

GSK Investigational Site

Sydney, New South Wales, 2145, Australia

Location

GSK Investigational Site

Sydney, New South Wales, 2150, Australia

Location

GSK Investigational Site

Melbourne, Victoria, Australia

Location

GSK Investigational Site

Perth, Western Australia, 6009, Australia

Location

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Trieste, Friuli Venezia Giulia, 34129, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20132, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20157, Italy

Location

GSK Investigational Site

Turin, Piedmont, 10122, Italy

Location

GSK Investigational Site

Florence, Tuscany, 50134, Italy

Location

GSK Investigational Site

Padua, Veneto, 35128, Italy

Location

MeSH Terms

Conditions

Macular Degeneration; Choroidal Neovascularization

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Choroid Diseases; Uveal Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 11, 2008
• Study Start: March 5, 2008
• Primary Completion: January 1, 2009
• Study Completion: June 17, 2009
• Last Updated: November 20, 2017
• Results First Posted: September 28, 2017

Record last verified: 2017-09

Locations

IT (6); US (16); BE (1); AU (4)