Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this randomized, single-dose, two-way evaluation is to compare the bioequivalence of a test cilostazol formulation to an equivalent oral dose of the commercially available cilostazol in a test population of 36 adult subjects under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 100 mg
DRUGPletal® 100 mg tablets
1 x 100 mg
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Sex: Male and Female; similar proportion of each preferred. Female subjects must be surgically sterile for at least six (6) months or postmenopausal for at least one (1) year. * Age: At least 18 years. * Weight: Body Mass Index (BMI) of 30 or less. * Qualifying subjects must be in good health and physical condition as determined by medical history, complete physical examination, and laboratory test, all obtained within four (4) weeks prior to study start. The subject may not have a history of significant past illness expected to affect the investigation. The normal status of subjects will be confirmed by the following procedures: * Laboratory Tests: Hemoglobin, hematocrit, RBC, WBC, differential count, serum electrolytes (Na, K, Cl), fasting blood glucose, BUN, bilirubin, creatinine, AST, ALT, LD, alkaline phosphatase, and urinalysis. HIV, Hepatitis B, Hepatitis C, and drugs of abuse testing will be done for screening purposes only. Urine drugs of abuse testing will be repeated at each check-in. Female subjects will have a serum pregnancy test done at screening and a urine pregnancy test prior to each study period at check-in. Laboratory values which are greater than 20% of the normal range will not qualify unless specifically accepted (with comment) by the Principal Investigator. Results of HIV, Hepatitis B, Hepatitis C, and drugs of abuse must be negative or non-reactive for the subject to qualify for the study. * Electrocardiogram A 12-lead electrocardiogram (ECG) will be obtained for all subjects. The original tracings, plus interpretation, will be included in the case report form packet. * Subjects must read and sign the Consent Form.
Exclusion criteria
* History of treatment for alcoholism, substance abuse, or drug abuse within past 24 months. * History of sensitivity to cilostazol, quinolones, or any antiplatelet drug. * History of malignancy, stroke, diabetes, cardiac, renal or liver disease or other serious illness. * History of GERD (gastroesophageal reflux disease), malabsorption syndrome, colon cancer, or chronic colitis, including Crohn's disease. * History of treatment for pulmonary obstruction or asthma within the past five (5) years. * History of severe headaches or migraines. * History of glaucoma. * History of chronic infectious disease. * History of psychiatric disorder. * History of thyroid disorder/disease. * History of hypertension. * Females who are capable of becoming pregnant or are lactating. * Inability to read and/or sign the consent form. * Treatment with any other investigational drug during the four (4) weeks prior to the initial dosing for this study. * Subjects who have donated blood within four (4) weeks prior to the initial dosing for this study. * Subjects who smoke or use tobacco products or are currently using nicotine products (patches, gums, etc.). Three months abstinence is required.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 96 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 96 hour period | Bioequivalence based on AUC0-inf |
| AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration | Blood samples collected over 96 hour period | Bioequivalence based on AUC0-t |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cilostazol (Test) First Cilostazol 100 mg Tablets (test) dosed in first period followed by Pletal® 100 mg Tablets (reference) dosed in second period. | 18 |
| Pletal® (Reference) First Pletal® 100 mg Tablets (reference) dosed in first period followed by Cilostazol 100 mg Tablets (test) dosed in second period | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 1 | 0 |
| Washout: 7 Days | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Cilostazol (Test) First | Pletal® (Reference) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 18 Participants | 36 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 17 Participants | 15 Participants | 32 Participants |
| Region of Enrollment United States | 18 participants | 18 participants | 36 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 16 Participants | 15 Participants | 31 Participants |
Outcome results
Primary
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 96 hour period
Population: Data from subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cilostazol | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 8670 ng*h/mL | Standard Deviation 3626 |
| Pletal® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 8974 ng*h/mL | Standard Deviation 3147 |
90% CI: [90.47, 98.43]
Primary
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 96 hour period
Population: Data from subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cilostazol | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration | 8430 ng*h/mL | Standard Deviation 3507 |
| Pletal® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration | 8634 ng*h/mL | Standard Deviation 3104 |
90% CI: [91.52, 100.08]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 96 hour period
Population: Data from subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cilostazol | Cmax - Maximum Observed Concentration | 536 ng/mL | Standard Deviation 147 |
| Pletal® | Cmax - Maximum Observed Concentration | 543 ng/mL | Standard Deviation 145 |
90% CI: [92.32, 104.61]