Pharmacodynamics
Conditions
Keywords
Clopidogrel, Platelet inhibition, Platelet aggregation
Brief summary
The purpose of this study is to compare the pharmacodynamic effect of clopidogrel on the platelet inhibition and the pharmacokinetic profiles of clopidogrel carboxylic acid metabolite between generic and reference clopidogrel products in Thai healthy volunteers
Detailed description
Platelet aggregation (ex vivo) were measured by using Whole blood impedence aggregometry (Chrono-log®) and VerifyNow® P2Y12 assay. Plasma concentration of clopidogrel carboxylic acid metabolite were measured by High performance liquid chromatography (HPLC).
Interventions
DRUGGeneric clopidogrel product Apolets®
* Clopidogrel 75 mg once daily for 7 days * Blood collection at 0 (before dosing), 1, 2, 4, 6, 8, 12, 24 hours after the last dose, administered at day 7
DRUGOriginal clopidogrel product Plavix®
* Clopidogrel 75 mg once daily for 7 days * Blood collection at 0 (before dosing), 1, 2, 4, 6, 8, 12, 24 hours after the last dose, administered at day 7
Sponsors
Khon Kaen University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Age between 18 and 45 years * Body mass index between 18-25 kg/m2 * No clinically significant abnormalities, as confirmed on medical history; detailed physical examination; clinical laboratory analysis (blood hematology, biochemistry, prothrombin time, bleeding time, and urinalysis)
Exclusion criteria
* An allergy to any drug; and/or a history of drug and/or alcohol abuse. * Subjects who had donated blood within 3 months prior to the start of this study or had participated in another investigational drug study within 3 months prior to the start of this study * Participating subjects were instructed to abstain from the use of any drugs for at least 2 weeks before and throughout the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacodynamic Effect: The Platelet Inhibition Effect of Clopidogrel at the Various Times on Day 7 (0-24 Hours) (at Steady State) | Blood collection at 0 (before dosing), 1, 2, 4, 6, 8, 12, 24 hours after the last dose, administered at day 7 |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic Profiles: Area Under the Concentration-Time Curve (AUC 0-24) | Blood collection at 0 (before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours after the last dose, administered at day 7 |
| Pharmacokinetic Profiles: The Maximum Plasma Concentration (Cmax) | Blood collection at 0 (before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours after the last dose, administered at day 7 |
| Pharmacokinetic Profiles: Time to Maximum Plasma Concentration (Tmax) | Blood collection at 0 (before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours after the last dose, administered at day 7 |
Countries
Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants First intervention: Apolets® 75 mg tablet (Generic Clopidogrel Product first, wash out period for 14 days then Original Clopidogrel Product) Generic clopidogrel product Apolets®: -Clopidogrel 75 mg once daily for 7 days. Blood collection at 0 (before dosing), 1, 2, 4, 6, 8, 12, 24 hours after the last dose, administered at day 7 Wash out period: 14 days Second intervention: Plavix® 75mg tablet (Original Clopidogrel Product first, wash out period for 14 days then Generic Clopidogrel Product) Original clopidogrel product Plavix®: -Clopidogrel 75 mg once daily for 7 days. Blood collection at 0 (before dosing), 1, 2, 4, 6, 8, 12, 24 hours after the last dose, administered at day 7 | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Intervention (7 Days) | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants |
| Age, Continuous | 29.43 years STANDARD_DEVIATION 7.21 |
| BMI | 22.12 kg/m^2 STANDARD_DEVIATION 2.75 |
| Region of Enrollment Thailand | 31 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 31 | 0 / 31 |
| serious Total, serious adverse events | 0 / 31 | 0 / 31 |
Outcome results
Primary
Pharmacodynamic Effect: The Platelet Inhibition Effect of Clopidogrel at the Various Times on Day 7 (0-24 Hours) (at Steady State)
Time frame: Blood collection at 0 (before dosing), 1, 2, 4, 6, 8, 12, 24 hours after the last dose, administered at day 7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Generic Clopidogrel Product | Pharmacodynamic Effect: The Platelet Inhibition Effect of Clopidogrel at the Various Times on Day 7 (0-24 Hours) (at Steady State) | 1853.58 percent inhibition*hour | Standard Deviation 673.95 |
| Original Clopidogrel Product | Pharmacodynamic Effect: The Platelet Inhibition Effect of Clopidogrel at the Various Times on Day 7 (0-24 Hours) (at Steady State) | 1892.84 percent inhibition*hour | Standard Deviation 657.22 |
Secondary
Pharmacokinetic Profiles: Area Under the Concentration-Time Curve (AUC 0-24)
Time frame: Blood collection at 0 (before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours after the last dose, administered at day 7
Secondary
Pharmacokinetic Profiles: The Maximum Plasma Concentration (Cmax)
Time frame: Blood collection at 0 (before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours after the last dose, administered at day 7
Secondary
Pharmacokinetic Profiles: Time to Maximum Plasma Concentration (Tmax)
Time frame: Blood collection at 0 (before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours after the last dose, administered at day 7