NCT05642845

Bioequivalence Study of Two Formulations of Atorvastatin Film-coated Tablets 40 mg in Healthy Volunteers Under Fasting Conditions

Randomized Crossover Four Period Single Dose Full Replicative Bioequivalence Study of Two Formulations Atorvastatin Film-coated Tablets 40 mg (Pharmtechnology LLC, Republic of Belarus) and Liprimar® Film-coated Tablets 40 mg (Manufacturer: Pfizer Pharmaceuticals LLC, Puerto Rico, LLC "Polysan Scientific and Technological Pharmaceutical Firm; RU Holder: Pfizer Inc, USA) in Healthy Volunteers Under Fasting Conditions

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: Pharmtechnology LLC · Industry
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

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 A subject who withdraws or is withdrawn during the pretrial evaluations but before receiving the first dose (the test or the reference product) in Period 1 will not be considered as a drop-out and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.

Conditions

• Bioequivalence

Interventions

Type	Name	Description
DRUG	Atorvastatin film-coated tablet 40 mg	Atorvastatin is manufactured by Pharmtechnology LLC, Republic of Belarus. Each tablet contains 40 mg of atorvastatin.
DRUG	Liprimar® film-coated tablet 40 mg	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.

Timeline

• Start date: 2022-11-19
• Primary completion: 2022-12-21
• Completion: 2023-06-05
• First posted: 2022-12-08
• Last updated: 2024-01-11

Locations

1 site across 1 country: Russia