Cardiovascular Disease
Conditions
Keywords
bioequivalence, SB224326, clopidogrel, Relative bioavailability
Brief summary
Clopidogrel is a potent anti-thrombotic drug that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. This is an open-label, randomized, single dose, three-way cross over, six sequence study to investigate the relative bioavailability of two 75 milligrams (mg) clopidogrel tablet formulations (clopidogrel SB224326 test formulation 1 \[Clop F1\] and clopidogrel SB224326 test formulation 2 \[Clop F2\]) compared with the reference product (innovator) in healthy human subjects. A total of 18 healthy human subjects will be randomized, such that approximately 14 evaluable subjects complete the study. Total duration in the study for each subject will be approximately 8 weeks from screening to the follow-up visit.
Interventions
DRUGClop F1
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
DRUGClop F2
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
DRUGInnovator
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Adult subjects aged between 18 and 65 years of age inclusive, at the time of signing the informed consent. * Healthy, non-smoker, as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. * A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>=50 kilograms (kg) and Body mass index (BMI) within the range 19 - 24.9 kg/square meter (m\^2) (inclusive). * Healthy male or female subjects: MALES: Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until 24 hours after the last dose of study medication: a) Vasectomy with documentation of azoospermia. b) Male condom plus partner use of one of the contraceptive following options: Contraceptive subdermal implant, Intrauterine device or intrauterine system, Oral Contraceptive, either combined or progestogen alone, Injectable progestogen, Contraceptive vaginal ring, Percutaneous contraceptive patches, This is an all inclusive list of those methods that meet the GlaxoSmithKline (GSK) definition of highly effective: having a failure rate of less than 1% per year when used consistently and, correctly and, when applicable, in accordance with the product label. For non-product methods (e.g. male sterility), the investigator determines what is consistent and correct use. The GSK definition is based on the definition provided by International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. FEMALES: Eligible to participate, if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies: a) Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy, Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. b) Reproductive potential and agrees to follow one of the options listed below in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until 24 hours after the last dose of study medication and completion of the follow-up visit. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of plasma pharmacokinetic (PK) parameters: AUC(0 ∞), AUC(0 t) and Cmax | Day 1: pre-dose, 0.25, 0.5, 0.75, 1.00, 1.33, 1.67, 2, 2.5, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00, 24.00 (Day 2) hours post-dose of each treatment period | The following PK parameters were measured: area under the plasma concentration-time curve from time zero to infinity (AUC\[0 ∞\]), area under the plasma concentration-time curve from time zero to last time point with measurable concentration (AUC\[0 t\]) and maximum observed plasma concentration (Cmax) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood pressure as a measure of safety and tolerability | Up to 8 weeks | Blood pressure will be measured at predose, 0.50, 1.00, 2.00, 4.00, and 24.00 hours post-dose. Post dose blood pressure to be taken plus or minus 30 minutes of each timepoint. |
| Pulse rate as a measure of safety and tolerability | Up to 8 weeks | Pulse rate will be measured at predose, 0.50, 1.00, 2.00, 4.00, and 24.00 hours post-dose. Post dose pulse rate to be taken plus or minus 30 minutes of each timepoint. |
| Number of subjects with adverse events and serious adverse events | From start of study medication until follow up (Up to 5 weeks) | An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was an event of possible drug-induced liver injury. |
| Composite of plasma PK parameters: time of occurrence of Cmax (tmax), percentage of AUC(0 ∞) obtained by extrapolation (%AUCex) and terminal phase half-life (t1/2) | Day 1: pre-dose, 0.25, 0.5, 0.75, 1.00, 1.33, 1.67, 2, 2.5, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00, 24.00 (Day 2) hours post-dose of each treatment period | Pre-dose PK blood samples will be collected within 60 minutes prior to dose. Post dose blood samples will be collected within 2 minutes. |
| Composite of clinical chemistry parameters as a measure of safety | Up to 8 weeks | The following clinical chemistry assessments will be performed: blood urea nitrogen (BUN), creatinine, fasting glucose, potassium, sodium, calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total and direct bilirubin, total protein, and albumin. |
| Composite of urinalysis parameters as measured by dipstick method and microscopic examination | Up to 8 weeks | Dipstick method will be used to measure pH, glucose, protein, blood and ketones. Microscopic examination will be performed if blood or protein is abnormal. |
| Composite of hematology parameters as a measure of safety | Up to 8 weeks | The following hematology assessments will be performed: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, white blood cells (WBC) (absolute), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), neutrophils, lymphocytes, monocytes, eosinophils, and basophils. |
Countries
India
Outcome results
None listed