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A. Capone, Macugen AMD Study Group; Intravitreous Pegaptanib Sodium (MacugenTM) in Patients With Age–Related Macular Degeneration (AMD): Safety and Pharmacokinetics . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2362.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To characterize the safety, tolerability, and pharmacokinetics of the pegylated anti–vascular endothelial growth factor (VEGF) aptamer pegaptanib sodium when administered as 3 mg intravitreous injections every 6 weeks for 30 weeks to patients with subfoveal choroidal neovascularization secondary to AMD. Methods: 3 mg pegaptanib sodium/study eye was administered by injection every 6 weeks for 30 weeks in 37 patients. Safety assessments included adverse events (AEs), ocular inflammation, intraocular pressure, visual acuity, blood pressure measurements, laboratory testing, and serum anti–pegaptanib IgG antibody determinations. After the first and fourth injections, serial blood samples were obtained for quantification of pegaptanib plasma concentrations. Results: Few systemic AEs were noted, and no clinically significant effects on blood pressure or urine protein were found. Mild or moderate ocular AEs that were related to the injection procedure were reported in most patients (84%). No clinically significant ocular inflammation was seen, and no anti–pegaptanib IgG antibodies were detected. No apparent accumulation of pegaptanib in plasma following multiple doses was noted given similar systemic exposure (mean peak plasma concentrations: ∼75 ng/mL and mean areas under the concentration–time curve: ∼25 µg.hr/mL) for the first and fourth doses. The mean apparent terminal half–life was 10 days, suggesting that pharmacologically adequate pegaptanib vitreous levels would be achieved in most patients for 6 weeks after each 0.3 mg dose, the dose intended for treatment. Conclusions: Pegaptanib sodium was well tolerated with no evidence of systemic VEGF inhibition (i.e., no systemic hypertension or proteinuria) and no clinically significant ocular inflammation. As previously seen in phase 3 trials, most ocular AEs were related to the injection procedure itself, and were mild or moderate in severity. The recommended dose from the pivotal efficacy trials is 0.3 mg, a 10–fold lower dose than the dose tested here.
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