Bioequivalence Study of Montelukast, 5 mg Chewable Tablets (Pharmtechnology LLC, Belarus), and Singulair®, 5 mg Chewable Tablets (Merck Sharp & Dohme B.V., the Netherlands), in Healthy Volunteers Under Fasting Conditions
Condition: Healthy Adults
Study type: Interventional
Phase: Phase 1

Summary: 
      This is an open-label, randomized, single-center, single-dose, crossover, in two periods and
      in two sequences comparative study, where each participant is randomly assigned to the
      reference or the test formulation in each period of the study (sequences Test-Reference (TR)
      or Reference-Test (RT)), in order to evaluate if both formulations are bioequivalent.
    

Detailed description: 
      The objective of this study is to establish if two formulations of montelukast are
      bioequivalent. Also monitoring, registration and evaluation of adverse events will be
      performed.

      The test formulation is Montelukast, 5 mg сhewable tablets (Pharmtechnology LLC, Belarus).
      The reference formulation is Singulair®, 5 mg сhewable tablets (Merck Sharp & Dohme B.V., the
      Netherlands). 34 healthy adult volunteers of both genders, with age ranging from 18 to 45
      years old, will be divided into two cohorts with equal number of participants (17). Each
      participant in a cohort will receive single tablet (5 mg of montelukast) of the test or the
      reference product with 200 ml of water after an overnight fast of at least 10 hours,
      according to the pre-defined randomization list, i. e. 17 participants in each cohort will
      receive the test product and 17 participants in each cohort will receive the reference
      product in each of two periods of the study. Participants will fast 4 hours after
      administration of the study drugs during each study period. Standardized meals will be
      provided in each study period. Water will not be accessible to the participants 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 will be collected withing 30 minutes before dosing
      and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75, 3.00, 3.25, 3.5, 4.00, 4.5, 5.00, 6.00,
      8.00, 12.00, 16.00, 24.00 hours after dosing (total number: 20). The washout period will be 7
      days.

      At the bio-analytical stage, a validated High Performance Liquid Chromatography with Tandem
      Mass Spectrometry detection (HPLC/MS) method will be used to determine plasma concentrations
      of montelukast. At all stages of working with biological samples measures to protect
      montelukast from daylight exposure should be provided.

      ANOVA will be performed on log transformed pharmacokinetic parameters Cmax, Area Under the
      pharmacokinetic Curve from the beginning of the study to the time of the last measured
      concentration (AUC0-t) and 90% confidence interval will be constructed for the ratio of
      geometric 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 montelukast falls within the acceptable range of 80.00% to 125.00% for Cmax and
      AUC0-t
    

Intervention name(s): Montelukast; Singulair
Intervention type(s): Drug; Drug
Intervention description(s): Montelukast, 5 mg Chewable Tablets, manufactured by Pharmtechnology LLC, Republic of Belarus; Singulair, 5 mg Chewable Tablets, marketed by Merck Sharp & Dohme B.V., the Netherlands
Other intervention name(s): The test product; The reference product
Intervention MeSH terms: Montelukast
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Other
Keywords: Bioequivalence; Montelukast; Singulair