Pharmacokinetic Comparison of an Orally Disintegrating Film Formulation With a Film-Coated Tablet Formulation of Sildenafil in Healthy Korean Subjects: A Randomized, Open-Label, Single-Dose, 2-Period Crossover Study

Abstract

BACKGROUND: An orally disintegrating film (ODF) formulation of sildenafil was recently developed in Korea. This formulation is expected to enhance dosing convenience and increase patient compliance while yielding pharmacokinetics comparable to those of the conventional film-coated tablet (FCT) formulation. OBJECTIVE: The goal of this study was to compare the pharmacokinetic profiles of a newly developed ODF formulation with those of a FCT formulation of sildenafil in healthy Korean male volunteers. METHODS: This was a randomized, open-label, single-dose, 2-period crossover study conducted in 2 parts. Eligible subjects were between the ages of 20 and 50 years and within 20% of their ideal weight; subjects were equally divided into parts 1 and 2. Each subject received a single dose of the ODF and FCT formulations of sildenafil orally in a fasted state (part 1, 50 mg; part 2, 100 mg), with a 7-day washout period between the formulations. Blood samples were collected up to 24 hours postdosing. Pharmacokinetic parameters were determined for sildenafil and its active metabolite (N-desmethyl sildenafil). Adverse events (AEs) were evaluated based on subject interviews and physical examinations. RESULTS: Among the 120 enrolled subjects (60 subjects for each part), 110 completed the study (part 1, n = 53; part 2, n = 57). In both parts, all the primary pharmacokinetic parameters were included in the range for assumed bioequivalence in sildenafil, yielding 90% CI ratios of 91.07% to 120.67% for AUC0-last and 86.68% to 122.93% for Cmax in part 1, and 101.68% to 114.78% for AUC0-last and 93.76% to 109.76% for Cmax in part 2. In part 1, headache was the most frequently noted AE, occurring in 3 subjects with both the test and the reference formulations. All other AEs occurred in <3 subjects. In part 2, nasal congestion was the most frequently observed AE (7 with the test formulation and 1 with the reference formulation), followed by abnormal vision (4 with the test formulation and 4 with the reference formulation), headache (4 with the test formulation and 4 with the reference formulation), and rhinorrhea (5 with the test formulation). All other AEs occurred in <3 subjects. CONCLUSIONS: The study findings suggest that the pharmacokinetics of the ODF formulation of sildenafil do not differ significantly from those of the conventional FCT formulation (50 and 100 mg) in these healthy Korean male subjects. The 2 formulations were well tolerated in both parts of the study, with no serious AEs observed. ClinicalTrials.gov identifier: NCT01769638.