title: Pilot and pivotal study to evaluate the bioequivalence of two paroxetine 40 mg tablet formulations in healthy Chinese subjects.
abstract: The purpose of this study was to conduct a pilot study in order to obtain reliable results for further planning of a well-designed pivotal trial comparing the bioequivalence (BE) of two paroxetine tablet formulations in healthy Chinese subjects. Before conducting the pivotal trial, the pilot trial enrolled 14 subjects to help in study design, establishing the recruitment period, determining pharmacokinetics (PK) time points and sample size, and assessing BE of the two formulations. The single-center, randomized, open-label, single-dose, two period crossover study with a 7-day washout interval was conducted after obtaining information from the fasted pilot trial in 72 healthy volunteers for a pivotal study under fed and fasted conditions, respectively. There were 19 PK sample collection time points employed in both the pilot and pivotal trials. A sensitive and specific liquid chromatography- tandem mass spectrometry (LC-MS/ MS) method was developed and validated for determining paroxetine in human plasma. BE between two articles was determined by calculating 90% confidence intervals (CIs) for the ratio of Cmax 91.38 - 110.39% for the pilot trial, 99.81 - 114.08% for pivotal trial under fasted condition, and 94.06 - 110.41% for pivotal trial under fed condition, AUC(0-t) 96.06 - 110.52% for pilot study, 100.88 - 113.05% for the pivotal trial under fasted condition, and 97.08 - 106.06% for pivotal study under fed condition, and AUC(0-∞) 96.17 - 110.42% for the pilot study, 100.85 - 112.81% for the pivotal trial under fasted condition and 97.22 - 106.14% for the pivotal study under fed condition, respectively. These values for the test and reference products are within the 80 - 125% interval proposed by FDA and EMEA. It was concluded that the proposed method was successfully applied to a PK study in healthy Chinese volunteers, and results showed from both the pilot and pivotal studies that the two paroxetine formulations are bioequivalent in their rates and extent of absorption.
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. zhanfss88@hotmail.com
authors.forename: Shengjun
authors.initials: S
authors.lastname: Zhang
authors.forename: Quancheng
authors.initials: Q
authors.lastname: Kan
authors.forename: Jian Guo
authors.initials: JG
authors.lastname: Wen
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Yuqiao
authors.initials: Y
authors.lastname: Sheng
authors.forename: Yidong
authors.initials: Y
authors.lastname: Li
authors.forename: Suke
authors.initials: S
authors.lastname: Sun
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Lv
authors.forename: Yuanchao Derek
authors.initials: YD
authors.lastname: Zhang
authors.forename: Kun
authors.initials: K
authors.lastname: Qian
authors.forename: Zhongping John
authors.initials: ZJ
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010865:Pilot Projects; D018401:Sample Size; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics*; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency
chemical_list: D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D013607:Tablets