Bioequivalence Study of Tadalafil Oral Soluble Film and Tadalafil Tablet in Healthy Chinese Volunteers Under Fasting Conditions

在空腹条件下,健康中国志愿者服用他达拉非口服速溶膜和他达拉非片剂的生物等效性研究

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Abstract

To investigate if a newly developed tadalafil oral soluble film (OSF) was bioequivalent to the approved tadalafil tablets, a clinical study was conducted in healthy Chinese male volunteers under fasting conditions. In this study, 36 volunteers were randomized into three groups and received one tadalafil tablet, one tadalafil OSF with water, or one OSF without water in each period. The dosages were all 10 mg. Blood samples were collected and centrifuged. Plasma concentrations of tadalafil were determined by liquid chromatography tandem mass spectrometry. Pharmacokinetic (PK) parameters including maximum plasma concentration (C(max)), area under the concentration versus time curve (AUC) from dosing to the last sampling time (AUC(0-t)), AUC from administration to infinity (AUC(0-∞)), time to C(max), half-life and terminal elimination rate constant were calculated. Primary PK parameters including C(max), AUC(0-t), and AUC(0-∞) were logarithmically transformed and an analysis of variance was applied to determine the bioequivalence between the reference and test formulation, as well as bioequivalence between tadalafil OSF administered with or without water. Safety was assessed by adverse events (AEs), serious adverse events (SAEs) and results of laboratory tests and examinations. The 90% confidence intervals of geometric mean ratios of primary PK parameters were all within the bioequivalence range of 80.00%-125.00%. AEs were mild or moderate and no SAEs were reported. Under fasting conditions, the test OSF formulation was bioequivalent to the reference tablets, and the test OSF administered with water was bioequivalent to that without water. All investigational formulations were well tolerated in the study. Trial Registration: chinadrugtrials.org.cn (CTR20181044).

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