Clinical evaluation of pazopanib eye drops in healthy subjects and in subjects with neovascular age-related macular degeneration

• Published in: Retina (Philadelphia, Pa.) Vol. 34; no. 9; p. 1787
• Main Authors: Singh, Rishi, Wurzelmann, John I, Ye, Li, Henderson, Linda, Hossain, Mohammad, Trivedi, Trupti, Kelly, Deborah S
• Format: Journal Article
• Language: English
• Published: United States 01.09.2014
• Subjects: Administration, Topical; Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - pharmacokinetics; Biological Availability; Double-Blind Method; Female; Healthy Volunteers; Humans; Male; Middle Aged; Ophthalmic Solutions; Protein-Tyrosine Kinases - antagonists & inhibitors; Pyrimidines - adverse effects; Pyrimidines - pharmacokinetics; Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors; Retina - drug effects; Sulfonamides - adverse effects; Sulfonamides - pharmacokinetics; Tissue Distribution; Visual Acuity - drug effects; Wet Macular Degeneration - drug therapy; Wet Macular Degeneration - metabolism; Young Adult
• ISSN: 1539-2864
• DOI: 10.1097/IAE.0000000000000179

To evaluate pazopanib 10 mg/mL eye drops (pazopanib) in healthy subjects and in subjects with previously untreated subfoveal choroidal neovascularization secondary to age-related macular degeneration. Study 1 (single center, randomized, placebo-controlled, double-masked) included 3 cohorts of 12 to 13 healthy subjects each who instilled pazopanib or placebo 4 times daily for 2 weeks. Study 2 (multicenter open-label) included 19 subjects with neovascular age-related macular degeneration who instilled pazopanib 4 times daily for 12 weeks. Both studies evaluated pharmacokinetics and safety. Study 2 also evaluated efficacy. Steady-state concentrations of pazopanib in plasma seemed to be reached by Week 2. At Week 4 (Study 2), there were no meaningful changes from baseline in the mean central retinal thickness (37.9 μm) or best-corrected visual acuity (0.1 letters) (primary endpoint), retinal morphology, choroidal neovascularization size, or total lesion size. Complement Factor H genotype had no effect on changes from baseline in the best-corrected visual acuity or central retinal thickness. The most common pazopanib-related ocular adverse events included eye irritation (Study 1, n = 7) and instillation site pain (Study 2, n = 3). No serious adverse events were reported. Pazopanib was well tolerated. In subjects with previously untreated neovascular age-related macular degeneration, pazopanib instilled 4 times daily as monothereapy did not seem to improve the best-corrected visual acuity or decrease the central retinal thickness.