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Rishi Singh, John Wurzelmann, Li Ye, Michael Fries, John Norris, Mohammad Hossain, Trupti Trivedi, Deborah Kelly; Topical Pazopanib for the Treatment of Previously Untreated Choroidal Neovascularization due to Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2178.
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To evaluate the potential of topical ocular pazopanib, a tyrosine kinase inhibitor, to reduce retinal edema and improve visual acuity (VA) in subjects with previously untreated subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) over 4 weeks and to characterize the safety/tolerability of the study drug over 12 weeks.
In a multicountry Phase 2a open-label trial, 19 eligible subjects were treated with pazopanib eye drops 10 mg/mL (1 drop), 4 times daily (QID) for 12 weeks. VA, optical coherence tomography (OCT), and safety were assessed weekly in Month 1, biweekly in Month 2, and once in Month 3. The primary assessments were the changes from baseline after 4 weeks of treatment in central retinal thickness (CRT) as measured by OCT, and best-corrected visual acuity (BCVA) as determined by the electronic ETDRS method.
There were no meaningful changes from baseline at Week 4 in mean (standard deviation [SD]) CRT (38  µm) or mean (SD) BCVA (0  letters) (primary endpoint). Similarly, there were no meaningful changes from baseline in any of the additional parameters measured by OCT, or in CNV or total lesion size as measured by fluorescein angiography. There were no obvious differences observed for changes from baseline in BCVA or CRT between subjects with the CFH Y402H T allele (CT and TT genotypes combined) and subjects with the CC genotype. In the study eye, 8 of 19 subjects experienced 9 ocular adverse events (AEs), 1 of which was severe (macular edema due to progression of the underlying disease). Nine subjects discontinued due to protocol-defined stopping criteria and received rescue medication. Nine subjects reported nonocular AEs, 1 of which was severe. No deaths or serious AEs were reported. Steady-state concentrations appeared to have been reached by Week 2 after administration of study drug.
In subjects with previously untreated neovascular AMD, pazopanib eye drops 10 mg/mL QID as monotherapy did not appear to improve BCVA or decrease CRT. There was no meaningful change from baseline in CRT, retinal morphology, CNV size, or total lesion size. Pazopanib eye drops 10 mg/mL were generally safe and well tolerated when instilled QID for 12 weeks.
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