Fasted Bioavailability Study of Cilostazol Tablets, 50mg

Study Overview
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Brief Summary
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The purpose of this study is to evaluate and compare the relative bioavailability of a test formulation of cilostazol tablets to an equivalent dose of Pletal® (cilostazol) tablets after a single oral dose administered under fasting conditions.

Detailed Description
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The purpose of this study is to evaluate and compare the relative bioavailability of a test formulation of cilostazol tablets to an equivalent dose of Pletal® (cilostazol) tablets after a single oral dose administered under fasting conditions. Thirty-two non-smoking, non-obese, healthy male and female volunteers between the ages of 18 and 55 will be randomly assigned in a crossover fashion to receive each of two cilostazol dosing regimens in sequence with a 7 day washout period between dosing periods. On the morning of Day 1, after an overnight fast of at least 10 hours, subjects will receive either a single oral dose of the test formulation, cilostazol (2 x 50 mg tablets), or a single oral dose of the reference formulation, Pletal® (2 x 50 mg tablets). After a 7 day washout period on the morning of Day 8, following an overnight fast of at least 10 hours, subjects will receive the alternate regimen. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of cilostazol. Blood sampling will then continue on a non-confined basis at 36 and 48 hours post-dose. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout the confinement portion of the study for adverse reactions to the study drug and/or procedures. Blood pressure and pulse will be measured before dosing and at 3 and 24 hours post-dose. All adverse events whether elicited by query, spontaneously reported, or observed by clinic staff will be evaluated by the investigator and reported in the subject's case report form.

Official Title
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A Comparative Bioavailability Study of Cilostazol Tablets, 50mg, Under Fasting Conditions

Conditions
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Therapeutic Equivalency, Healthy

Intervention / Treatment
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* Drug: Cilostazol 50 mg Tablets
* Drug: Cilostazol (Pletal®) 50 mg Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults 18-55 years of age Non-smoking Non-pregnant (post-menopausal, surgically sterile or using effective contraceptive measures) No more than 15% plus or minus from ideal weight for subject's height and elbow breadth as defined by the Metropolitan Life Insurance Company Statistical Bulletin. Extrapolations, if required, to be conducted according to BASi Standard Operating Procedures Medically healthy on the basis of medical history and physical examination within 30 days prior to the start of the study Test results from blood chemistry, hematology, and urinalysis performed within 30days prior to the start of the study within clinically acceptable limits At screening, subjects must have blood pressure and pulse rate within the following ranges: Systolic blood pressure 90-140mmHg; Diastolic blood pressure 50-90mmHg; Pulse 45-100 bpm An acceptable electrocardiogram (EKG): sinus rhythm with no evidence of AV block or ischemic changes Exclusion Criteria: Prescription drug use (excluding hormonal contraceptives) within 14 days prior to drug administration, each period Aspirin ingestion within 7 days prior to drug administration, each period Use of any over-the-counter preparations, herbal remedies, and/or nutritional supplements within 7 days prior to drug administration, each period Consumption of grapefruit juice or grapefruit-containing products within 72 hours prior to drug administration , each period Consumption of alcohol within 24 hours prior to drug administration, each period Consumption of caffeine within 10 hours prior to drug administration, each period Female subjects must not be pregnant or nursing; and must be surgically sterile; one year post-menopausal; or on hormonal contraceptive agent(s), a diaphragm or condom with spermicidal foam or jelly, or IUD for at least three months prior to drug administration and agree to use the same method of contraception for at least 1 month after the last drug administration Subjects with a history or presence of significant organ system (cardiovascular, neurological, hepatic, hematopoietic, renal, pulmonary, endocrine, or gastrointestinal) disorders, or ongoing infectious diseases History of hypersensitivity or adverse reactions to cilostazol (Pletal®), or other related drugs Recent (12 month) history or evidence of alcoholism or drug abuse Positive urine screening of drugs of abuse Positive results to Human Immunodeficiency Virus (HIV) or Hepatitis B surface Antigen (HBsAg) tests Participation in another clinical trial in the previous 30 days before day 1 of this study Donation of blood in the previous 30 days before day 1 of this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cilostazol 50 mg Tablets<br>A single dose of cilostazol (2 x 50 mg tablets) administered after an overnight fast of at least 10 hours. | Drug: Cilostazol 50 mg Tablets<br>* Cilostazol (2 x 50 mg tablets) administered after an overnight fast of at least 10 hours<br>|
| Experimental: Cilostazol (Pletal® ) 50 mg Tablets<br>A single dose of Cilostazol (Pletal® tablets, 2 x 50 mg ) administered after an overnight fast of at least 10 hours. | Drug: Cilostazol (Pletal®) 50 mg Tablets<br>* Cilostazol (Pletal® Tablets, 2 x 50mg) administered after an overnight fast of at least 10 hours.<br>* Other names: Pletal®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) | The maximum or peak concentration that cilostazol (test and reference product) reaches in the plasma. | serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours after drug administration. | 
| Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | The area under the plasma concentration versus time curve, from time 0 to the time of the last measurable concentration (t), as calculated by the linear trapezoidal rule. | serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours after drug administration. | 
| Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] | The area under the plasma concentration versus time curve from time 0 to infinity. AUC(0-∞) was calculated as the sum of AUC(0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant. | serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours after drug administration. |