Fasted Bioequivalence Study of Clopidogrel Film-coated Tablets, 75 mg in 48 Healthy, Adult Male and Female Subjects.

Fasting, Comparative, Open-label, Randomized, Four-period, Two-sequence, Bioequivalence Study of Сlopidogrel Bisulfate Film-coated Tablets, 75 mg (JSC Farmak, Ukraine) vs Plavix® 75 mg Film-coated Tablets in Healthy Adult Subjects

This study was designed to compare bioequivalence of the Test Product Clopidogrel bisulfate, film-coated tablets, 75 mg (JSC Farmak, Ukraine) and Reference Product Plavix® 75 mg film-coated tablets (Sanofi Winthrop Industrie, France) in healthy male and female volunteers under fasting conditions.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: Сlopidogrel bisulfate film-coated tablets, 75 mg (JSC Farmak, Ukraine); Drug: Plavix® 75 mg film-coated tablets (Sanofi Winthrop Industrie, France)

Detailed Description

An open, comparative, randomized, four-period, two- sequence, two-way crossover clinical trial to evaluate the Bioequivalence of Single Doses of Test Product Clopidogrel bisulfate, film-coated tablets, 75 mg (JSC Farmak, Ukraine) and Reference Product Plavix® 75 mg film-coated tablets (Sanofi Winthrop Industrie, France) in healthy adult male and female volunteers under fasting conditions.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Ukraine
  • Kharkiv, Ukraine
    • Clinical and Diagnostics Center of National University of Pharmacy (NUPh).

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Healthy males and non-pregnant and no breast-feeding females1), ≥18 and ≤50 years of age (on the day of Informed Consent). Caucasian race.
• Subject had provided his/her written informed consent before the start of any screening procedures.
• Subject was available for the whole study and to follow all the requirements of the study protocol.
• Body Mass Index (BMI) 18.5 to 30.0 kg/m2, inclusive (on the day of screening).
• Subject without any acute or chronic diseases of the cardiovascular system, neuroendocrine system, kidney, liver, gastrointestinal tract, respiratory system.
• Subjects in good health, as determined by screening medical history, physical examination, vital signs assessments (pulse rate, systolic and diastolic blood pressure, and body temperature) and 12-lead electrocardiogram (ECG). Minor deviations outside the reference ranges were acceptable, if deemed not clinically significant by the Investigator
• The results of fluorography are within normal ranges (no more than 10 months before inclusion in the study).
• Sitting blood pressure is within normal ranges: 100 -140 mm Hg for systolic PB, 55 -95 mm Hg. for diastolic blood pressure (BP) at screening;
• Acceptance of use of contraceptive measures during the whole study by both female and male subjects.
• Non-smoker
• Subject is available to comply with the general dietary restrictions throughout the study.

Exclusion Criteria:

• History of severe allergy or allergic reactions to the study Investigational Medicinal Product (IMP), its excipients or related drugs.
• Aggravated allergic history
• History of any clinically significant disease or disorder or surgical intervention which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• A positive result of Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), and / or (human immunodeficiency virus) HIV or syphilis tests during screening procedure.
• A positive results of urine drug of abuse test (amphetamine, methamphetamine, morphine, marijuana, cocaine).
• Positive result of alcohol breath test
• Positive urine cotinine test
• The values of the standard parameters of the laboratory and instrumental examinations are outside the normal range and are clinically relevant or require additional examination and interpretation.
• Pregnancy (positive urine pregnancy test result in women)
• Lactation period (for women).
• Acute infectious diseases in less than 28 days before the first dosing.
• Use of any medication for a period of 14 days before the first dosing.
• Donation of blood within 30 days before the first dosing.
• Participation in any other clinical study during last 90 days.
• Other reasons when participation of a volunteer in the study is undesirable in the opinion of the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; Сlopidogrel bisulfate film-coated tablets, 75 mg (JSC Farmak, Ukraine)	Drug: Сlopidogrel bisulfate film-coated tablets, 75 mg (JSC Farmak, Ukraine); One film-coated tablet was administrated orally with 240 ml of water after an overnight fast; Other Names: Trombonet
Active Comparator: Treatment B; Plavix® 75 mg film-coated tablets (Sanofi Winthrop Industrie, France)	Drug: Plavix® 75 mg film-coated tablets (Sanofi Winthrop Industrie, France); One film-coated tablet was administrated orally with 240 ml of water after an overnight fast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Сmax	maximum plasma concentration observed	up to 36 hours post-administration
AUC0-t	area under the plasma concentration versus time curve calculated by the trapezoidal rule from sampling time zero to sampling time of the last measurable plasma concentration	up to 36 hours post-administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tmax	the time of the maximum plasma drug concentration	up to 36 hours post-administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
λz	apparent first-order elimination	up to 36 hours post-administration
t1/2	the elimination or terminal half-life	up to 36 hours post-administration
AUC0-∞	area under the plasma concentration versus time curve from time zero to infinity	up to 36 hours post-administration

Collaborators and Investigators

• Sponsor: Joint Stock Company "Farmak"

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2018
• Primary Completion (Actual): August 27, 2018
• Study Completion (Actual): August 27, 2018

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: November 17, 2021
• First Posted (Actual): November 18, 2021

Study Record Updates

• Last Update Posted (Actual): November 18, 2021
• Last Update Submitted That Met QC Criteria: November 17, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: pharmacokinetics; bioequivalence; Clopidogrel; generic drugs; Film-coated Tablets
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: FK-CLP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No