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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00612456
First received: January 29, 2008
Last updated: February 28, 2013
Last verified: February 2013
  Purpose

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


Condition Intervention Phase
Macular Degeneration
Drug: Pazopanib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Double-masked, Randomized, Parallel-group Study to Investigate the Pharmacodynamics, Safety, and Systemic Pharmacokinetics of Pazopanib Drops, Administered for 28 Days to Adult Subjects With Neovascular Age-related Macular Degeneration.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • central retinal thickness measured by OCT, an imaging technique [ Time Frame: at each weekly visit for 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • clinical laboratory tests [ Time Frame: screening, baseline, D29 and follow-up ] [ Designated as safety issue: No ]
    Hematology, clinical chemistry and urinalysis parameters and other tests

  • Retinal morphology, neovascular size, and lesion size and characteristics [ Time Frame: measured at screening and week 4 ] [ Designated as safety issue: No ]
  • plasma pazopanib concentration-time data [ Time Frame: baseline at each on-treatment day, sparse PK sampling on D15 or D22 ] [ Designated as safety issue: No ]
    pharmacokinetic parameters will be determined, as data permit: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-t)], and Cmin.

  • Safety endpoints include, clinical monitoring and adverse event reporting. [ Time Frame: at visits, f/u and ongoing during study ] [ Designated as safety issue: No ]
  • Change in visual acuity (number of letters read on standardized ETDRS charts). [ Time Frame: ongoing during study ] [ Designated as safety issue: No ]
  • Change in retinal morphology (i.e. CNV, intraretinal cysts, intraretinal fluid, subretinal fluid, and retinal pigment epithelial detachment) as determined by OCT. [ Time Frame: ongoing during study ] [ Designated as safety issue: No ]
  • Change in neovascular size, lesion size and characteristics (fibrosis, atrophy, blood) as measured by fluorescein angiography and fundus photography. [ Time Frame: ongoing during study ] [ Designated as safety issue: No ]
  • cardiac monitoring [ Time Frame: screening, D15 and follow-up ] [ Designated as safety issue: No ]
    electrocardiogram

  • vital signs [ Time Frame: measured weekly for 4 weeks ] [ Designated as safety issue: No ]
    heart ate and blood pressure

  • complete ophthalmic examination [ Time Frame: screening, D15, D29 and follow-up visit ] [ Designated as safety issue: No ]
    Examination of eyelids and lashes, Pupil, motility and confrontation visual field examination, Slit lamp evaluation of anterior ocular structures, Intraocular pressure (IOP) measurement, Dilated Fundus Examination

  • visual acuity [ Time Frame: measured weekly for 4 weeks ] [ Designated as safety issue: No ]
    Refraction and visual acuity will be measured using standardized ETDRS visual acuity charts

  • liver function tests [ Time Frame: measured weekly for 4 weeks ] [ Designated as safety issue: No ]
    AST (SGOT), ALT (SGPT), Alkaline phosphatase, Direct bilirubin, total biblirubin.


Enrollment: 70
Study Start Date: March 2008
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Pazopanib eye drops formulation 5 mg/mL daily for 28 days
Drug: Pazopanib
Pazopanib eye drops formulation
Other Name: pazopanib
Experimental: Arm 2
Pazopanib eye drop formulation 5mg/mL TID for 28 days
Drug: Pazopanib
Pazopanib eye drops formulation
Other Name: pazopanib
Experimental: Arm 3
Pazopanib eye drop formulation 2mg/mL TID for 28 days
Drug: Pazopanib
Pazopanib eye drops formulation
Other Name: pazopanib

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00612456

Locations
United States, Arizona
GSK Investigational Site
Tuscon, Arizona, United States, 85704
United States, California
GSK Investigational Site
Beverly Hills, California, United States, 90211
GSK Investigational Site
Pasadena, California, United States, 91105
GSK Investigational Site
Sacramento, California, United States, 95841
United States, Florida
GSK Investigational Site
Ft. Lauderdale, Florida, United States, 33334
GSK Investigational Site
Winter Haven, Florida, United States, 33880
United States, Indiana
GSK Investigational Site
Indianapolis, Indiana, United States, 46280
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02111
United States, Michigan
GSK Investigational Site
Ann Arbor, Michigan, United States, 48105
GSK Investigational Site
Grand Rapids, Michigan, United States, 49525
United States, New Jersey
GSK Investigational Site
Toms River, New Jersey, United States, 08755
United States, North Carolina
GSK Investigational Site
Winston-Salem, North Carolina, United States, 27157
United States, Pennsylvania
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78705
GSK Investigational Site
Houston, Texas, United States, 77030
United States, Utah
GSK Investigational Site
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00612456     History of Changes
Other Study ID Numbers: MD7108240
Study First Received: January 29, 2008
Last Updated: February 28, 2013
Health Authority: Italy: Ministry of Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
angiogenesis
pazopanib,
age-related macular degeneration (AMD),
vascular endothelial growth factor (VEGF),
choroidal neovascularization (CNV),

Additional relevant MeSH terms:
Macular Degeneration
Eye Diseases
Retinal Degeneration
Retinal Diseases

ClinicalTrials.gov processed this record on October 30, 2014