Bioequivalence Study of Clavamox, Film-coated Tablets, 875 mg + 125 mg Pharmtechnology LLC, Belarus), and Augmentin®, Film-coated Tablets, 875 mg + 125 mg (GlaxoSmithKline Trading CJSC, Russia), in Healthy Volunteers Under Fasting Conditions
Condition: Bioequivalence
Study type: Interventional
Phase: Phase 1

Summary: 
      This was an open-label, randomized, single-center, single-dose, two-treatment, two-sequence,
      two-period, crossover, comparative study, where each subject was randomly assigned to the
      reference or the test formulation in each period of the study (sequences RT or TR), in order
      to evaluate if both formulations are bioequivalent.The study was conducted in multiple
      groups.
    

Detailed description: 
      The objective of this study was to establish if two formulations of amoxicillin + clavulanic
      acid combination are bioequivalent. Also monitoring, registration and evaluation of adverse
      events was performed. The test formulation was Clavamox, Coated Tablets, 875 mg + 125 mg
      (Pharmtechnology LLC, Belarus). The reference formulation was Augmentin®, Coated Tablets, 875
      mg + 125 mg (GlaxoSmithKline Trading CJSC, Russia). 56 healthy adult volunteers of both
      genders, with age ranging from 18 to 45 years old, were divided into two cohorts with equal
      number of subjects (28). Each subject in a cohort received single tablet (875 mg of
      amoxicillin and 125 mg of clavulanic acid) of the test or the reference products with 200 ml
      of water after an overnight fast of at least 10 hours, according to the pre-defined
      randomization list, i. e. 14 subjects in each cohort received the test product and 14
      subjects in each cohort received the reference product. Subjects fasted 4 hours after
      administration of the study drugs during each study period. Standardized meals were provided
      in each study period. Water was not accessible to the subjects 1 hour prior to administration
      of the study drugs and 2 hours after administration of the study drugs in each period. In
      each period blood samples were collected before dosing and 0.25, 0.5, 0.75, 1.00, 1.25, 1.5,
      1.75, 2.00, 2.33, 2.67, 3.00, 3.5, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00 hours after dosing
      (total number: 19). The washout period was 7 days. At the current bio-analytical stage, a
      validated HPLC/MS/MS method are used to determine plasma concentrations of two analytes
      (amoxicillin and clavulanic acid). ANOVA will be performed on log transformed pharmacokinetic
      parameters Cmax, AUC0-t and 90% confidence interval will be constructed for the ratio of
      geometric least square means of the test and the reference products, obtained from the
      log-transformed data. Bioequivalence will be concluded if the ratio estimate as well as its
      90% confidence interval for each analyte, both falls within the acceptable range of 80.00% to
      125.00% for Cmax and AUC0-t.
    

Intervention name(s): Clavamox; Augmentin®
Intervention type(s): Drug; Drug
Intervention description(s): Clavamox, Film-coated Tablets, 875 mg + 125 mg, manufactured by Pharmtechnology LLC, Belarus; Augmentin®, Film-coated Tablets, 875 mg + 125 mg, marketed by GlaxoSmithKline Trading CJSC, Russia
Other intervention name(s): the test product; the reference product
Intervention MeSH terms: Amoxicillin-Potassium Clavulanate Combination
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Other
Keywords: bioequivalence; amoxicillin; clavulanic acid; Augmentin