Singh Rishi, Wurzelmann John I, Ye Li, Henderson Linda, Hossain Mohammad, Trivedi Trupti, Kelly Deborah S
*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.
Retina. 2014 Sep;34(9):1787-95. 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.
在健康受试者以及年龄相关性黄斑变性继发的未经治疗的中心凹下脉络膜新生血管受试者中评估10 mg/mL帕唑帕尼滴眼液（帕唑帕尼）。
研究1（单中心、随机、安慰剂对照、双盲）包括3组队列，每组12至13名健康受试者，他们每天滴注帕唑帕尼或安慰剂4次，持续2周。研究2（多中心开放标签）包括19名年龄相关性黄斑变性新生血管受试者，他们每天滴注帕唑帕尼4次，持续12周。两项研究均评估了药代动力学和安全性。研究2还评估了疗效。
血浆中帕唑帕尼的稳态浓度似乎在第2周时达到。在第4周（研究2），平均中心视网膜厚度（37.9μm）或最佳矫正视力（0.1字母）（主要终点）、视网膜形态、脉络膜新生血管大小或总病变大小与基线相比无显著变化。补体因子H基因型对最佳矫正视力或中心视网膜厚度相对于基线的变化无影响。最常见的与帕唑帕尼相关的眼部不良事件包括眼部刺激（研究1，n = 7）和滴注部位疼痛（研究2，n = 3）。未报告严重不良事件。
帕唑帕尼耐受性良好。在未经治疗的年龄相关性黄斑变性新生血管受试者中，每天滴注4次的帕唑帕尼单药治疗似乎并未改善最佳矫正视力或降低中心视网膜厚度。
