title: Clinical evaluation of pazopanib eye drops in healthy subjects and in subjects with neovascular age-related macular degeneration.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: *Department of Ophthalmology, Cleveland Clinic, Cleveland, OH; †Research & Development, GlaxoSmithKline, Research Triangle Park, NC; ‡Research & Development, GlaxoSmithKline, King of Prussia, PA; and §Research & Development, GlaxoSmithKline, Collegeville, PA.
authors.forename: Rishi
authors.initials: R
authors.lastname: Singh
authors.forename: John I
authors.initials: JI
authors.lastname: Wurzelmann
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Linda
authors.initials: L
authors.lastname: Henderson
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hossain
authors.forename: Trupti
authors.initials: T
authors.lastname: Trivedi
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Kelly
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007191:Indazoles; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012160:Retina / Q000187:drug effects; D013449:Sulfonamides / Q000009:adverse effects / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014792:Visual Acuity / Q000187:drug effects; D057135:Wet Macular Degeneration / Q000188:drug therapy / Q000378:metabolism*; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D009883:Ophthalmic Solutions; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor