Bioequivalence Study of Two Formulations of Atorvastatin Film-coated Tablets 40 mg in Healthy Volunteers Under Fasting Conditions
Condition: Bioequivalence
Study type: Interventional
Phase: Phase 1

Summary: 
      This is an open-labeled, randomized, two period, single-center, crossover, full replicative,
      comparative study, where each participant will be randomly assigned to the reference
      (Liprimar®, 40 mg film-coated tablets) or the test (Atorvastatin, 40 mg film-coated tablets)
      formulation in each period of study (sequences Test-Reference (TR) or Reference-Test (RT)),
      in order to evaluate if both formulations are bioequivalent.
    

Detailed description: 
      This is an open-labeled, randomized, two period, crossover, a single-center, full
      replicative, comparative, single-dose study, in which 50 healthy adult subjects will receive
      one of the study treatments during each study period.

      The objective of this study is to determine the bioequivalence of two different formulations
      of atorvastatin after a single oral dose administration under fasting conditions.

      Subject eligibility for this study will be determined at the screening visit and eligible
      subjects will be admitted to the clinical research unit at least 12 hours prior to drug
      administration for each study period.

      A subject who withdraws or is withdrawn during the pretrial evaluations but before receiving
      the first dose (the test or the reference product) in Period 1 will not be considered as a
      drop-out and will not be included in the final database. Standbys should be recruited and
      available to replace any subject who withdraws prior to the first drug administration.
      On-study drop-outs will not be replaced.

      Eligible subjects will be randomized to one of two treatment sequences. There will be two
      sequences in the study: TR and RT, where T = the test product, R = the reference product.

      For each study period, subjects will receive a single 40 mg oral dose of atorvastatin (the
      test or the reference formulation). Study participants will be aware they will receive
      different formulations of the same drug, without being informed which product (Test or
      Reference) is being administered. For each subject, all scheduled postdose activities and
      assessments will be performed relative to the time of study drug administration.

      Fasting will continue for at least 4 hours following drug administration, after which a
      standardized lunch will be served. Next meals will be provided for subjects in 6 hours, 9
      hours and 12 hours after drug administration.

      Water will be provided as needed until 1 hour predose. Water will be allowed beginning 2
      hours after the administration of the drug.

      A total of 23 blood samples will be collected (one tube of 6 mL each) in each study period
      for pharmacokinetic (PK) assessments. The first blood sample will be collected prior to drug
      administration while the others will be collected up to 72 hours after drug administration.

      Atorvastatin plasma concentrations will be measured according to a validated bioanalytical
      method.

      Subjects are to be discharged from the clinic after the 24-hour following drug
      administration. However, they may be advised to stay at the clinical site for safety reasons,
      if judged necessary by the physician in charge. Subjects will return to the clinical site for
      each of the 3 remaining blood samples.

      Statistical analysis of all PK parameters will be based on an ANOVA model. Bioequivalence
      boundaries will be extended. The maximum extension range is 69.84%-143.19%. In order to
      expand the criterion of acceptability, it is necessary to confirm that the Cmax variability
      of the reference drug in the study actually exceeds 30%. Expansion of acceptable
      bioavailability limits based on intraindividual variability does not extend to AUC0-t, the
      limits of which, regardless of variability, should be limited to an interval of
      80.00-125.00%. The duration of plasma sampling required by the protocol is expected to ensure
      that the condition "AUC0-t is ≥ 80% of AUC0-∞" is met.

      The bioequivalence of the studied drugs will be confirmed for the parent substance,
      atorvastatin, and for its metabolites, orthohydroxyatorvastatin and parahydroxyatorvastatin.
    

Intervention name(s): Atorvastatin film-coated tablet 40 mg; Liprimar® film-coated tablet 40 mg
Intervention type(s): Drug; Drug
Intervention description(s): Atorvastatin is manufactured by Pharmtechnology LLC, Republic of Belarus. Each tablet contains 40 mg of atorvastatin.; Liprimar® is manufactured by Pfizer Pharmaceuticals LLC, Puerto Rico, LLC "Polysan Scientific and Technological Pharmaceutical Firm; RU holder: Pfizer Inc, USA. Each tablet contains 40 mg of atorvastatin.
Other intervention name(s): The test product; The reference product
Intervention MeSH terms: Atorvastatin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Other