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

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00612456

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 II

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:

Genetics Home Reference related topics: age-related macular degeneration X-linked juvenile retinoschisis

MedlinePlus related topics: Macular Degeneration

Drug Information available for: Pazopanib

U.S. FDA Resources

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:	February 2008
Study Completion Date:	January 2009
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Pazopanib Pazopanib eye drops formulation	Drug: Pazopanib Pazopanib eye drops 5mg/ml dailyfor 28 days Other Name: pazopanib Drug: Pazopanib Pazopanib eye drops 5mg/ml TID for 28 days Other Name: pazopanib Drug: Pazopanib Pazopanib eye drops 2mg/ml TID for 28 days 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

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

Show 26 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00612456 History of Changes
Other Study ID Numbers:	MD7108240
Study First Received:	January 29, 2008
Last Updated:	September 15, 2011
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
Retinal Degeneration
Retinal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on February 09, 2012