Bioequivalence Study of Two Formulations of Clopidogrel Film-coated Tablets 75 mg in Healthy Male Subjects Under Fasting Conditions

NCT05934799 | Completed Phase 1

• 1 other identifier: CLPDRL-CPI-2021_FRMT
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bioequivalence

Outcome Measures

Primary Outcomes (2)

• Cmax of сlopidogrel 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, 15 min, 20 min, 30 min, 40 min, 50 min, 1.00, 1.15, 1.30, 2.00, 2.30, 3.00, 4.00, 6.00, 8.00, 10.00 12.00, 16.00, 24.00 hours after each drug administration.

• AUC0-t of сlopidogrel 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, 1.15, 1.30, 2.00, 2.30, 3.00, 4.00, 6.00, 8.00, 10.00 12.00, 16.00, 24.00 hours after each drug administration.

Study Arms (2)

Sequence TR

OTHER

30 subjects assigned to the sequence TR will receive a single 75 mg dose of the test product Clopidogrel (1 x 75 mg film-coated tablet), marked as T in the sequence, in Period 1 and Period 3, and a single 75 mg dose of the reference product Plavix® (1 x 75 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: Clopidogrel film-coated tablet 75 mg; Drug: Plavix® film-coated tablet 75 mg

Sequence RT

OTHER

30 subjects assigned to the sequence RT will receive a single 75 mg dose of the reference product Plavix® (1 x 75 mg tablet), marked as R in the sequence, in Period 1 and Period 3 and a single 75 mg dose of the test product Clopidogrel (1 x 75 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: Clopidogrel film-coated tablet 75 mg; Drug: Plavix® film-coated tablet 75 mg

Interventions

Clopidogrel film-coated tablet 75 mg DRUG

Clopidogrel is manufactured by Pharmtechnology LLC, Republic of Belarus. Each tablet contains 75 mg of clopidogrel.

Also known as: The test product

Sequence RT; Sequence TR

Plavix® film-coated tablet 75 mg DRUG

Plavix® is manufactured by Sanofi Winthrop Industry, France; holder RU: Sanofi-Aventis Group S.A., France. Each tablet contains 75 mg of clopidogrel.

Also known as: The reference product

Sequence RT; Sequence TR

Eligibility Criteria

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

You may qualify if:

• Healthy european men aged between 18 to 45 years
• signed informed consent
• 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)
• 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 сlopidogrel or excipients that are part of any of the investigational drugs, or intolerance to these components;
• 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 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;
• increased risk of bleeding (eg, frequent nosebleeds, recent trauma, surgery, or other pathological condition);
• a history of active pathological bleeding (eg, peptic ulcer, intracranial hemorrhage);
• 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;
• donation of plasma or blood (450 ml or more) less than 2 months (60 days) before taking the drug in the first period;
• 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;

Sponsors & Collaborators

• Pharmtechnology LLC: lead
• ClinPharmInvest, LLC: collaborator

Study Sites (1)

State Autonomous Healthcare Facility of the Yaroslavl Region "Clinical Hospital No. 2"

Yaroslavl, Yaroslavl Oblast, 150010, Russia

Location

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: June 28, 2023
• First Posted: July 7, 2023
• Study Start: June 16, 2023
• Primary Completion: July 23, 2023
• Study Completion: October 10, 2023
• Last Updated: November 30, 2023

Record last verified: 2023-06

Locations

RU (1)