Comparative Bioavailability Study of Two Oral Formulations of Clopidogrel
Information source: Hospital Universitario Dr. Jose E. Gonzalez
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Comparative Bioavailability of Clopidogrel Tablets
Intervention: Clopidogrel bisulfate (Drug); Clopidogrel (Drug)
Phase: Phase 1
Status: Terminated
Sponsored by: Hospital Universitario Dr. Jose E. Gonzalez Official(s) and/or principal investigator(s): Lourdes Garza Ocañas, MD PhD, Principal Investigator, Affiliation: Hospital Universitario Jose E Gonzalez
Summary
Background: Clopidogrel, a potent inhibitor of adenosine diphosphate-induced platelet
activation, is widely used to prevent and reduce the risk of thrombotic events. Objective:
the aim of the present study is to evaluate the bioequivalence of two oral formulations of
75 mg clopidogrel tablets. Method: The study is an open, randomized, single-dose, two-period
crossover trial conducted on 32 healthy Mexican volunteers in a fasted state. A single oral
dose of the test or reference drug will be followed by a 7 day washout period, after which
subjects will receive the alternative formulation. Blood samples were collected up to 24 h
after dosing. In order to determine bioequivalence, the plasma concentrations of clopidogrel
carboxylic acid metabolite was determined using high-performance liquid
chromatography-tandem mass spectrometry area under the plasma concentration time curve from
zero to the last quantifiable level (AUC0-t), area under the plasma concentration time curve
extrapolated to infinity (AUC0-∞), maximum plasma concentration (Cmax), the plasma
elimination half-life (Tmax) and plasma half-life (T1/2) were calculated for both
formulations.
Clinical Details
Official title: Bioavailability of Two Oral Formulations of Clopidogrel: A Randomized, Open Label, Single Dose, Two-Period, Crossover Comparison in Healthy Mexican Volunteers
Study design: Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Health Services Research
Primary outcome: maximum plasma concentration (Cmax)
Secondary outcome: area under the plasma concentration time curve from zero to the last quantifiable level (AUC0-t),area under the plasma concentration time curve extrapolated to infinity (AUC0-∞)
Detailed description:
Study procedure In each period, the subjects arrived at the clinical/unit site on the day
before the commencement of the study and were randomized using Excel® 2007 to receive the
test formulation followed by the reference formulation, or viceversa. No food was allowed
from 10 h before until at least 4 h after drug administration. On the subsequent morning, a
peripheral venous 21G catheter was inserted in the antecubital vein of the subjects and
blood samples were collected (zero time). The subjects then received a single 75 mg tablet
of either the test or the reference formulation, given with 250 mL water. Blood samples were
collected at 0. 16, 0. 33, 0. 5, 0. 66, 0. 83, 1, 1. 5, 1. 75, 2, 2. 5, 3, 6, 8, 12, 16 and 24 h
after drug administration. The blood samples were collected in coded EDTA tubes and plasma
was obtained by centrifugation (2,053 g for 10 min at 5 C), after which the plasma was
immediately transferred to prelabeled vials and stored at or below - 70 After a week of
washout, the alternative formulation was administered to the subjects and samples were drawn
and analyzed as before.
Eligibility
Minimum age: 18 Years.
Maximum age: 40 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Male or female and age is between 18 and 40 years, inclusive.
2. Females must have negative results for pregnancy tests performed: at Screening on a
urine specimen obtained within 2 weeks prior to initial study drug administration,
and prior to dosing on urine sample obtained on Study Day - 1 of each period
3. Body Mass Index (BMI) is 19 to 26, inclusive. BMI is calculated as weight in kg
divided by the square of height measured in meters.
4. A condition of general good health, based upon the results of a medical history,
physical examination, vital signs, laboratory profile and a 12-lead electrocardiogram
(ECG).
5. Must voluntarily sign and date each informed consent, approved by an Independent
Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of
any screening or study-specific procedures.
Exclusion Criteria:
1. History of significant sensitivity to any drug.
2. Requirement for any over-the-counter and/or prescription medication, vitamins and/or
herbal supplements, on a regular basis.
3. Use of any medications, vitamins and/or herbal supplements, within the 1-week period
prior to study drug administration.
4. Pregnant or breastfeeding female.
5. Recent (6-month) history of drug or alcohol abuse.
6. Positive test result for hepatitis B surface antigen (HBsAg) or HIV antibodies (HIV
Ab). Negative HIV status will be confirmed at Screening and the results will be
maintained confidentially by the study site.
7. Use of known inhibitors (e. g., ketoconazole) or inducers (e. g., carbamazepine) of
cytochrome P450 3A (CYP3A) within 1 month prior to study drug administration.
8. Positive screen for drugs of abuse, or alcohol or nicotine or positive and clinically
significant urine adulterants test.
9. Receipt of any drug by injection within 30 days or within a period defined by 5
half-lives, whichever is longer, prior to study drug administration.
10. History of epilepsy, any clinically significant cardiac, respiratory (except mild
asthma), renal, hepatic, gastrointestinal, hematologic or psychiatric disease or
disorder, or any uncontrolled medical illness.
11. History of gastric surgery, vagotomy, bowel resection or any surgical procedure that
might interfere with gastrointestinal motility, pH or absorption.
12. Donation or loss of 550 mL or more blood volume (including plasmapheresis) or receipt
of a transfusion of any blood product within 8 weeks prior to study drug
administration.
13. Receipt of any investigational product within 8 weeks prior to study drug
administration or 7 half-lives, whichever is longer.
14. Consumption of alcohol within the 3-day period prior to study drug administration.
15. Consumption of grapefruit or grapefruit products, Seville oranges, star fruit and
quinine/tonic water from 3 days prior to study drug administration.
16. Use of tobacco or nicotine-containing products within the 6-month period preceding
study drug administration.
17. Current enrollment in another clinical study.
18. Consideration by the investigator, for an reason, that the subject is an unsuitable
candidate to receive Ibuprofen
Locations and Contacts
Departamento de Farmacologia y Toxicologia, Monterrey, Nuevo Leon 64460, Mexico
Additional Information
Starting date: May 2008
Last updated: October 5, 2011
|