title: Pivotal Bioequivalence Study of Clopacin®, a Generic Formulation of Clopidogrel 75 mg Film-Coated Tablets.
abstract: BACKGROUND
  Clopacin(®) (Acino Pharma AG) is a proprietary, besylate salt and lactose-free formulation of the widely-used anti-platelet treatment, clopidogrel. This study aimed to evaluate the bioequivalence of Clopacin(®) with the originator as reference drug, using a guideline-compliant trial design: open-labeled, randomized, single-dose (clopidogrel 75 mg tablet), two-period, crossover trial in 48 healthy male volunteers, with a 7 day wash-out period.
  
  
  METHODS
  Plasma samples were collected at intervals and extracted before quantifying clopidogrel concentrations using a fully validated LC-MS/MS method. Bioequivalence of Clopacin(®) and the reference drug was established by comparison of the primary pharmacokinetic parameters, C max, AUC0-t, and AUC0-∞.
  
  
  RESULTS
  The parameter values were similar for the two products (analysis of variance) and provided Clopacin/reference ratios (least squares means) of >90% and 90% confidence intervals (CIs 84.64-105.50%, 90.43-111.22%, 88.75-110.71%, respectively) that were well within the limits set for defining bioequivalence, according to international guidelines. The respective Clopacin(®) and reference drug values for mean time to maximal plasma clopidogrel concentration (t max) were 0.83 and 0.91 h, and for terminal elimination half-life were 3.99 and 3.51 h. The intra-subject coefficients of variability for maximal plasma clopidogrel concentration (C max), area under the plasma clopidogrel concentration versus time curve, at 48 h (AUC0-t) and extrapolated to infinity (AUC0-∞) were 32.2%, 30.2%, and 28.9% (least square means), respectively, and the respective power values were 99.5%, 97.1%, and 95.3%.
  
  
  CONCLUSIONS
  This bioequivalence study provided robust clopidogrel pharmacokinetic data that established the bioequivalence of Clopacin(®) and the reference originator drug.
  
  
  BACKGROUND
  Acino Pharma AG (formerly Cimex AG).
authors.affiliation: Faculty of Medicine, Marburg University, Marburg, Germany. mcgregor@staff.uni-marburg.de.|OmniScience SA, 5 Rue Liotard, 1202, Geneva, Switzerland. mcgregor@staff.uni-marburg.de.
authors.forename: Gerard Patrick
authors.initials: GP
authors.lastname: McGregor
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D000077144:Clopidogrel; D018592:Cross-Over Studies; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D016568:Drugs, Generic; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Bioequivalence; Bioequivalence guidelines; Clopacin®; Clopidogrel; Clopidogrel besylate; Clopidogrel pharmacokinetics; Generic clopidogrel; Lactose-free clopidogrel formulation