A Study To Evaluate The Safety, Tolerability And Pk Of Pazopanib Eye Drops In Healthy Adult And Elderly Subjects.

NCT00463320 | Completed Phase 1

• 1 other identifier: MD7108238
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

This is a two-part study to evaluate the safety, tolerability and pharmacokinetics of single (Part A) and repeat (Part B) eye drop doses of pazopanib in healthy adult and elderly subjects.

Conditions

Macular Degeneration; Age-related Macular Degeneration

Keywords

Age-related macular degeneration (AMD),; vascular endothelial growth factor (VEGF)receptor (VEGFR); choroidal neovascularization,

Outcome Measures

Primary Outcomes (3)

• Ocular safety by observation and eye exams.

  at baseline, each dosing day and follow-up

• General safety by PE, VS, cardiac monitoring, clinical laboratory tests and adverse events reporting .

  day-1,5,10,14

• Pazopanib exposure by AUC and Cmax .

  day 1,14

Secondary Outcomes (6)

• Pazopanib exposure measured by secondary pharmacokinetic parameters at day 1 and 14.

• Safety endpoints include complete ophthalmic examination, vital signs (heart rate and blood pressure), cardiac monitoring (electrocardiogram), clinical laboratory tests, clinical monitoring and adverse event reporting.

• Change in visual acuity (number of letters read on standardized ETDRS charts).

• Change in retinal morphology (i.e. CNV, intraretinal cysts, intraretinal fluid, subretinal fluid, and retinal pigment epithelial detachment) as determined by OCT.

• Change in neovascular size, lesion size and characteristics (fibrosis, atrophy, blood) as measured by fluorescein angiography and fundus photography.

Interventions

Pazopanib eye drops and Allergen Refresh Plus eye drops DRUG

Eligibility Criteria

• Age: 30 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

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 D8 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.
• Male or female 50 years of age.
• Best-corrected ETDRS visual acuity in the study eye between 80 to 24 letters inclusive (approximately 20/25 to 20/320 or 4/5 to 4/63) at screening.
• A female subject is eligible to participate if she is of non-childbearing potential defined as either pre-menopausal with a documented tubal ligation or hysterectomy, or postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases of postmenopausal status a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory.
• Subject is willing and able to return for all study visits, and is willing and able to comply with all protocol requirements and procedures.
• Subject is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. If the subject is unable to read the consent form due to visual impairment then the consent must be read to the subject verbatim by person administering the consent, a family member or legally acceptable representative. If the subject is unable to provide written informed consent due to visual impairment, then written informed consent on behalf of the subject must be provided by a legally acceptable representative.
• (Note: Consent by legally acceptable representative is allowed where this is in accordance with local laws, regulations and ethics committee policy.)

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
• Active treatment in the fellow eye, with the exception of preservative-free artificial tears.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Fargo, North Dakota, 58104, United States

Location

GSK Investigational Site

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

Macular Degeneration; Choroidal Neovascularization

Interventions

Ophthalmic Solutions

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2007
• First Posted: April 20, 2007
• Study Start: March 1, 2007
• Study Completion: August 1, 2007
• Last Updated: March 19, 2012

Record last verified: 2011-02

Locations

US (2)