Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
This study will compare the relative bioavailability (rate and extent of absorption) of 50 mg Cilostazol Tablets manufactured by TEVA Pharmaceuticals Industries Ltd. and distributed by TEVA Pharmaceuticals USA with that of PLETAL Tablets manufactured by Otsuka Pharmaceuticals Co., Ltd. for Otsuka America Pharmaceutical, Inc. following a single oral dose (1 x 50 mg tablet) in healthy adult subjects administered under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 50 mg, single-dose fasting
DRUGPletal®
1 x 50 mg, single-dose tablet
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
* Screening Demographics: All volunteers selected for this study will be healthy men or women 18 years of age or older at the time of dosing. The volunteer's body mass index (BMI) is less than or equal to 30. * Screening Procedures: Each volunteer will complete the screening process within 28 days prior to Period I dosing. Consent documents for both the screening evaluation and HIV antibody determination will be reviewed, discussed, and signed by each potential participant before full implementation of screening procedures. Screening will include general observations, physical examination, demographics, medical and medication history, an electrocardiogram, sitting blood pressure and heart rate, respiratory rate and temperature. The physical examination will include, but may not be limited to, an evaluation of the cardiovascular, gastrointestinal, respiratory, and central nervous systems. * The screening clinical laboratory procedures will include: * Hematology: hematocrit, hemoglobin, RBC count, WBC count with differential, platelet count; * Clinical Chemistry: serum creatinine, BUN, glucose, AST(GOT), ALT(GPT), albumin, total bilirubin, total protein, and alkaline phosphatase. * HIV antibody and hepatitis B surface antigen and hepatitis C antibody screens; * Urinalysis: by dipstick; full microscopic examination if dipstick positive; and * Urine Drug Screen: ethyl alcohol, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates, and phencyclidine; * Serum Pregnancy Screen (female volunteers only). * Follicle Stimulating Hormone (FSH; female subjects only): verify postmenopausal status * If female and: * is postmenopausal for at least 1 year with postmenopausal status defined as: \> 60 years of age and amenorrheic for at least one year; if 60 years of age or younger, must also have a serum FSH level \>30 IU/L; or * is surgically sterile for at least 6 months (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).
Exclusion criteria
* Volunteers with a recent history of drug or alcohol addiction or abuse. * Volunteers with the presence of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease (as determined by the clinical investigators). * Volunteers whose clinical laboratory test values are outside the accepted reference range and when confirmed on re-examination are deemed to be clinically significant. * Volunteers demonstrating a positive hepatitis B surface antigen screen or a reactive HIV antibody screen. * Volunteers demonstrating a positive drug abuse screen when screened for this study. * Female volunteers demonstrating a positive pregnancy screen. * Female volunteers who are currently breastfeeding. * Volunteers with a history of allergic response(s) to cilostazol or related drugs. * Volunteers with a history of clinically significant allergies including drug allergies. * Volunteers with a clinically significant illness during 4 weeks prior to Period I dosing (as determined by the clinical investigators). * Volunteers who are currently using or report using tobacco products within 90 days prior to Period I dosing. * Volunteers who have taken any drug known to induce or inhibit hepatic drug metabolism in the 30 days prior to Period I dosing. * Volunteers who report donating greater than 150 mL of blood within 30 days prior to Period I dosing. All subjects will be advised not to donate blood for four weeks after completing the study. * Volunteers who have donated plasma (e.g. plasmapheresis) within 14 days prior to Period I dosing. All subjects will be advised not to donate plasma for four weeks after completing the study. * Volunteers who report receiving any investigational drug within 30 days prior to Period I dosing. * Volunteers who report taking any prescription medication or nonprescription medication in the 14 days or 7 days, respectively, prior to Period I dosing with the exception of topical products without systemic absorption. * Volunteers who have been on an abnormal diet during the 28 days prior to Period I dosing. * Volunteers who report an intolerance or direct venipuncture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 72 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 72 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 72 hour period | Bioequivalence based on AUC0-t |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cilostazol (Test) First Cilostazol 50 mg Tablets (test)dosed in first period followed by Pletal® 50 mg Tablets (reference) dosed in second period | 15 |
| Pletal® (Reference) First Pletal® 50 mg Tablets (reference) dosed in first period followed by Cilostazol 50 mg Tablets (test) dosed in second period | 15 |
| Total | 30 |
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 | 15 Participants | 15 Participants | 30 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 15 Participants | 14 Participants | 29 Participants |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 0 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Male | 15 Participants | 9 Participants | 24 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 72 hour period
Population: Data from all 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) | 5010.17 ng*h/mL | Standard Deviation 1508.03 |
| Pletal® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 5176.83 ng*h/mL | Standard Deviation 1435.42 |
90% CI: [91.04, 101.52]
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 72 hour period
Population: Data from all 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 | 4618.70 ng*h/mL | Standard Deviation 1416.6 |
| Pletal® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration | 4745.22 ng*h/mL | Standard Deviation 1370.01 |
90% CI: [92.13, 101.37]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cilostazol | Cmax - Maximum Observed Concentration | 376.46 ng/mL | Standard Deviation 115.88 |
| Pletal® | Cmax - Maximum Observed Concentration | 398.06 ng/mL | Standard Deviation 108.07 |
90% CI: [87.33, 99.86]