An Open-label, Blinded, Randomized Crossover Four Period Single Dose Full Replicative Bioequivalence Study of Two Formulations Clopidogrel Film-coated Tablets 75 mg (Pharmtechnology LLC, Republic of Belarus) and Plavix® Film-coated Tablets 75 mg (Manufacturer: Sanofi Winthrop Industry, France; Holder RU: Sanofi-Aventis Group S.A., France) in Healthy Volunteers Under Fasting Conditions.

CLPDRL-CPI-2021_FRMT

This is an open-labeled, randomized, four period, single-center, crossover, full replicative, comparative study, where each participant will be randomly assigned to the reference (Plavix®, 75 mg film-coated tablets) or the test (Clopidogrel, 75 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.

2023-06-16

2023-07-23

2023-10-10

Completed

Early phase I

60

Inclusion Criteria: 1. Healthy european men aged between 18 to 45 years 2. signed informed consent 3. Subjects having no clinically significant medical history and no clinically significant abnormalities in general physical examination, laboratory assessments and imaging studies 4. Body mass index 18.5-30 kg/m² 5. 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) 6. 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. 7. 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. Exclusion Criteria: 1. burdened allergic history, hypersensitivity to сlopidogrel or excipients that are part of any of the investigational drugs, or intolerance to these components; 2. clinically significant pathologies of the cardiovascular, bronchopulmonary, neuroendocrine systems, as well as diseases of the gastrointestinal tract, liver, kidneys and blood; 3. 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; 4. the presence of mental disorders, including a history; 5. surgical interventions on the gastrointestinal tract, with the exception of appendectomy; 6. acute infectious diseases that ended less than 4 weeks before taking the drug in the first period; 7. dehydration due to diarrhea, vomiting or other reason within the last 24 hours before taking the drug in the first period of the study; 8. 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; 9. 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; 10. use of any drugs including herbs and food additives, vitamins that can have a significant effect on the PK of сlopidogrel 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; 11. increased risk of bleeding (eg, frequent nosebleeds, recent trauma, surgery, or other pathological condition); 12. a history of active pathological bleeding (eg, peptic ulcer, intracranial hemorrhage); 13. taking known inhibitors or inducers of microsomal liver enzymes, especially those affecting the CYP2C19 isoenzyme (barbiturates, omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine, chloramphenicol) or antivirals less than 2 months before taking the drug in the first period; 14. donation of plasma or blood (450 ml or more) less than 2 months (60 days) before taking the drug in the first period; 15. consumption of caffeine and xanthine-containing drinks and products (tea, coffee, chocolate, cola, etc.), products containing poppy seeds, less than 48 hours before taking the drug in the first period; 16. consumption of alcohol and alcohol-containing foods and beverages less than 48 hours before taking the drug in the first period; 17. use of citrus fruits (including grapefruit and grapefruit juice) and cranberries (including juices, fruit drinks, etc.) less than 7 days before taking the drug in the first period; 18. intake of more than 10 units alcohol per week (1 unit of alcohol is equivalent to 500 ml of beer, 200 ml of dry wine or 50 ml of spirits ethyl 40%) or history of alcoholism, drug addiction, drug abuse; 19. following any low-sodium diet for 2 weeks before taking drug in the first period, or following a special diet (vegetarian, vegan, with limited salt intake) or lifestyle (night work, extreme physical activity); 20. inability to refrain from intensive physical activity and contact sports less than 24 hours before taking the drug in the first period; 21. smoking more than 10 cigarettes per day less than 24 hours before taking the drug in the first period; 22. participation in other clinical trials of drugs less than 3 months before taking the drug in the first period; 23. test positive for syphilis, hepatitis B, hepatitis C or HIV at the time of screening; 24. positive test for alcohol in exhaled air at screening; 25. positive urinalysis for the content of narcotic and potent substances during screening (opiates, morphine, barbiturates, benzodiazepines, cannabinoids/marijuana); 26. the value of standard laboratory and instrumental parameters that go beyond the reference values; 27. lack of intention of volunteers to comply with the Protocol requirements throughout the course of the study and/or lack, in the opinion of the Investigator, of the volunteers' ability to understand and evaluate the information on this study as part of the informed consent form signing process, in particular regarding the expected risks and possible discomfort; 28. mental, physical and other reasons that do not allow the subject to adequately assess their behavior and correctly fulfill the conditions of the study protocol; 29. tattooing and piercing within 30 days prior to first drug administration; 30. difficulty swallowing tablets; 31. difficulty with taking blood.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'primaryPurpose': 'OTHER', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 60, 'type': 'ACTUAL'}}

2023-11-30