Last updated: 11/07/2018 17:35:24
To evaluate the pharmacodynamics, safety, and pharmacokinetics of pazopanib drops in adult subjects with neovascular AMDN/A
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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.
Trial description: This is a 28 day study to evaluate the pharmacodynamic effect of pazopanib eye drops on the central retinal thickness of AMD patients
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
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
Timeframe: Baseline (Day -3 to -1) and Day 29
Secondary outcomes:
Number of participants with complete ophthalmic examination values of potential clinical concern
Timeframe: 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
Timeframe: Up to follow up (Day 46)
Number of participants with abnormal 12-lead electrocardiogram (ECG) findings
Timeframe: Day 15 and follow-up (Day 43)
Number of participants with clinical chemistry and hematology data of potential clinical concern
Timeframe: Up to follow-up Day 43
Number of participants with abnormal urinalysis data by dipstick analysis
Timeframe: Day 29 and follow-up (Day 43)
Number of participants with ocular adverse events, non-ocular adverse events, serious ocular adverse events and serious non-ocular adverse events
Timeframe: Up to follow-up (Day 43)
Change from Baseline in best corrected visual acuity (BCVA) [number of letter read on standardized early treatment of diabetic retinopathy study (ETDRS) charts at Day 29
Timeframe: Baseline (Day -3 to -1) and Day 29
Number of participants with change in retinal morphology (cystoid spaces, subretinal fluid and retinal pigment epithelial detachment) as determined by OCT
Timeframe: Day 29
Number of participants with change in characteristics (fibrosis, atrophy, blood) as measured by fundus photography (FP)
Timeframe: Day 29
Change from Baseline in neovascular size, total lesion size, fluorescein angiography (FA) leakage area of measurement, FA blood area of measurement as measured by FA at Day 29
Timeframe: Baseline (Day -3 to -1) and Day 29
Plasma pharmacokinetic parameter maximum observed concentration (Cmax)
Timeframe: Day 15 and Day 22
Plasma pharmacokinetic parameter time of occurrence of Cmax (tmax)
Timeframe: Day 15 and Day 22
Plasma pharmacokinetic parameter area under concentration time-curve from time zero to 6 hours (AUC [0-6)]
Timeframe: Day 15 and Day 22
Interventions:
Drug: Pazopanib
Enrollment:
70
Observational study model:
Not applicable
Primary completion date:
2009-27-01
Time perspective:
Not applicable
Clinical publications:
Danis R, McLaughlin M, Tolentino M, Staurenghi G, Ye L, Xu C-F, Kim R, Johnson M.Pazopanib Eye Drops: a Randomized Trial in Neovascular Age Related Macular Degeneration.Br J Ophthalmol.2014;98(2):172-178
Medical condition
Macular Degeneration
Product
pazopanib
Collaborators
Not applicable
Study date(s)
March 2008 to January 2009
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
50+ years
Accepts healthy volunteers
No
- 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)
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- 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.
Age-related macular degeneration patients diagnosed with subfoveal choroidal neovascularization in the study eye, with all of the following characteristics required:
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
- 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
Medical history or condition:
Trial location(s)
Location
GSK Investigational Site
Sydney, New South Wales, Australia, 2150
Status
Study Complete
Location
GSK Investigational Site
Grand Rapids, Michigan, United States, 49525
Status
Will Be Recruiting
Location
GSK Investigational Site
Ft. Lauderdale, Florida, United States, 33334
Status
Will Be Recruiting
Location
GSK Investigational Site
Sacramento, California, United States, 95841
Status
Study Complete
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02111
Status
Study Complete
Location
GSK Investigational Site
Sydney, New South Wales, Australia, 2145
Status
Study Complete
Location
GSK Investigational Site
Salt Lake City, Utah, United States, 84132
Status
Study Complete
Location
GSK Investigational Site
Toms River, New Jersey, United States, 08755
Status
Will Be Recruiting
Location
GSK Investigational Site
Winter Haven, Florida, United States, 33880
Status
Will Be Recruiting
Location
GSK Investigational Site
Ann Arbor, Michigan, United States, 48105
Status
Will Be Recruiting
Location
GSK Investigational Site
Beverly Hills, California, United States, 90211
Status
Will Be Recruiting
Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46280
Status
Will Be Recruiting
Location
GSK Investigational Site
Winston-Salem, North Carolina, United States, 27157
Status
Will Be Recruiting
Location
GSK Investigational Site
Houston, Texas, United States, 77030
Status
Will Be Recruiting
Location
GSK Investigational Site
Pasadena, California, United States, 91105
Status
Study Complete
Location
GSK Investigational Site
Tuscon, Arizona, United States, 85704
Status
Will Be Recruiting
Location
GSK Investigational Site
Trieste, Friuli-Venezia-Giulia, Italy, 34129
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Perth, Western Australia, Australia, 6009
Status
Study Complete
Location
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15213
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2009-27-01
Actual study completion date
2009-27-01
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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