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

NCT05642845 | Completed Phase 1

• 1 other identifier: ATVST-2021
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bioequivalence

Outcome Measures

Primary Outcomes (2)

• Cmax of atorvastatin in plasma after administration of the test and the reference products.

  Maximum observed concentration in plasma.

  Time points 0.00 (prior to each drug administration) and 10 min, 20 min, 30 min, 40 min, 50 min, 1.00, 2.00, 2.30, 3.00, 4.00, 5.00, 6.00, 8.00, 12.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration.

• AUC0-t of atorvastatin in plasma after administration of the test and the reference.

  Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration (TLQC) using the linear trapezoidal method.

  Time points 0.00 (prior to each drug administration) and 10 min, 20 min, 30 min, 40 min, 50 min, 1.00, 2.00, 2.30, 3.00, 4.00, 5.00, 6.00, 8.00, 12.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration.

Study Arms (2)

Sequence TR

OTHER

25 subjects assigned to the sequence TR will receive a single 40 mg dose of the test product Atorvastatin (1 x 40 mg film-coated tablet), marked as T in the sequence, in Period 1 and Period 3, and a single 40 mg dose of the reference product Liprimar® (1 x 40 mg film-coated tablet), marked as R in the sequence, in period 2 and Period 4. These treatments will be administered orally with approximately 200 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Atorvastatin film-coated tablet 40 mg; Drug: Liprimar® film-coated tablet 40 mg

Sequence RT

OTHER

25 subjects assigned to the sequence RT will receive a single 400 mg dose of the reference product Liprimar® (1 x 40 mg tablet), marked as R in the sequence, in Period 1 and Period 3 and a single 40 mg dose of the test product Atorvastatin (1 x 40 mg tablet), marked as T in the sequence, in period 2 and Period 4. These treatments will be administered orally with approximately 200 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Atorvastatin film-coated tablet 40 mg; Drug: Liprimar® film-coated tablet 40 mg

Interventions

Atorvastatin film-coated tablet 40 mg DRUG

Atorvastatin is manufactured by Pharmtechnology LLC, Republic of Belarus. Each tablet contains 40 mg of atorvastatin.

Also known as: The test product

Sequence RT; Sequence TR

Liprimar® film-coated tablet 40 mg DRUG

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.

Also known as: The reference product

Sequence RT; Sequence TR

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy european men or women aged between 18 to 45 years
• Subjects having no clinically significant medical history and no clinically significant abnormalities in general physical examination, laboratory assessments and imaging studies
• Body mass index 18.5-30 kg/m²
• The results of an X-ray or fluorographic examination of the chest organs within the normal range (the results of an examination carried out within 12 months before the start of the study may be provided)
• For female:
• Non-breastfeeding women
• the results of the examination of the mammary glands (palpation or mammography) within the normal range according to the data obtained within 12 months before the start of the study;
• Non-pregnant women (negative pregnancy test);
• adherence to reliable methods of contraception for female of childbearing potential: sexual continence, or condom + spermicide, or diaphragm + spermicide, started at least 14 days before the first dose of the study drug; intrauterine contraception is also a reliable method of contraception, installed at least 4 weeks before taking the study drugs in the first period;
• сonsent to use these methods of contraception during the study and within 14 days after taking the drug in the fourth period;
• women who do not use acceptable methods of contraception, if they are considered incapable of childbearing, will also be able to participate in the study: women who have undergone a hysterectomy or tubal ligation, women with a clinical diagnosis of infertility, and women who are in menopause (at least a year without menstruation in the absence of alternative pathologies that may cause the cessation of menstruation);
• in case of using contraceptives (injectable and oral hormonal contraceptives, subcutaneous hormonal implants or intrauterine hormonal therapeutic systems), the latter should be canceled at least 60 days before taking the drug in the first period.
• For male:
• \- consent to use a double barrier method of contraception (condom + spermicide) or complete sexual abstinence, as well as consent not to participate in sperm donation during the entire study and 14 days after taking the drug in the second period.
• Subjects are able to understand the requirements of the study, to sign a written informed consent, and also to accept all the restrictions imposed during the course of the study, and to agree to return for the required investigations.

You may not qualify if:

• burdened allergic history, hypersensitivity to atorvastatin or other statins, fibrates or excipients that are part of any of the investigational drugs, or intolerance to these components;
• hereditary lactose or galactose intolerance (for example, congenital deficiency lactase or glucose-galactose malabsorption);
• clinically significant pathologies of the cardiovascular, bronchopulmonary, neuroendocrine systems, as well as diseases of the gastrointestinal tract, liver, kidneys and blood;
• other diseases that, in the opinion of the researcher, may affect the absorption, distribution, metabolism or excretion of both drugs, or increase the risk of negative consequences for the volunteer;
• the presence of mental disorders, including a history;
• surgical interventions on the gastrointestinal tract, with the exception of appendectomy;
• acute infectious diseases that ended less than 4 weeks before taking the drug in the first period;
• dehydration due to diarrhea, vomiting or other reason within the last 24 hours before taking the drug in the first period of the study;
• clinically significant abnormalities on the ECG, the level of systolic blood pressure (SBP) measured in the sitting position at the time of screening ≤ 100 mm Hg or ≥ 139 mm Hg and / or diastolic blood pressure (DBP) ≤ 70 mm Hg or ≥ 89 mm Hg;
• heart rate less than 60 beats/min or more than 90 beats/min at the time of screening, respiratory rate less than 12 or more than 18 per minute at the time of screening, body temperature below 36.0 ° C or above 37.0 °C at the time of screening;
• use of medications:
• Injectable and oral hormonal contraceptives, subcutaneous hormonal implants, or intrauterine hormone therapy systems for 60 days before taking the medication in the first period;
• use of any drugs including herbs and food additives, vitamins that can have a significant effect on the PK of atorvastatin or data on the effect of which on the pharmacokinetics of lisinopril are unknown, as well as question the characterization of the volunteer as healthy, less than 14 days before taking the drug in the first period;
• CYP3A4 isoenzyme inducers or inhibitors (HIV protease inhibitors, azole antifungals, clarithromycin, erythromycin, phenytoin, carbamazepine, phenobarbital, St. John's wort, etc.) less than 30 days before taking the drug in the first period;
• donation of plasma or blood (450 ml or more) less than 2 months (60 days) before taking the drug in the first period;

Sponsors & Collaborators

• Pharmtechnology LLC: lead
• ClinPharmInvest, LLC: collaborator

Study Sites (1)

State Budgetary Healthcare Institution of the Yaroslavl Region "Clinical Hospital No. 2"

Yaroslavl, 150010, Russia

Location

Study Officials

• Natalia Moshnikova

  ClinPharmInvest, LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2022
• First Posted: December 8, 2022
• Study Start: November 19, 2022
• Primary Completion: December 21, 2022
• Study Completion: June 5, 2023
• Last Updated: January 11, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)