Pharmacokinetic Study of Once Daily PMR Compared to Twice Daily Cilostazol IR Tablets in Healthy Volunteers

Study Overview
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Brief Summary
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The study is designed to evaluate the bioequivalency between the test formulations of extended-release tablet of cilostazol (PMR) administered once-daily and the reference formulation of immediate-release tablet of cilostazol (Cilostazol) administered twice-daily in normal healthy male and female subjects under fasting conditions.

Official Title
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An Open-Label, Randomized, Three-Treatment, Three-Way Crossover Pharmacokinetic Study of Once Daily PMR Compared to Twice Daily Cilostazol IR Tablets in Healthy Volunteers

Conditions
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Intermittent Claudication

Intervention / Treatment
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* Drug: Cilostazol 100 mg
* Drug: PMR 150 mg
* Drug: PMR 200 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be 18 to 45 years of age, inclusive. Absence of diseases, such as heart failure, significant kidney impairment or a history of restricted blood flow to the heart, that could affect the study outcomes. Having a body mass index (BMI) within normal standard limits (18.5 24.9, inclusive). Willing and able to give informed consent to participate in the clinical study and comply with all study procedures, restrictions and attend all visits. Exclusion Criteria: History of bleeding tendency. Use of anticoagulant agent(s) within 1 month prior to screening. Use of tobacco or nicotine products within 6 months of screening. Intake of over the counter or prescription drugs (other than hormonal contraceptives) within 2 weeks prior to randomization. On any investigational drug(s) or therapeutic device(s) within 30 days preceding screening; or anticipating use of any of these therapies during the course of the study (other than the study products). History of substance abuse, such as alcohol, IV drugs, and inhaled drugs, within 1 year prior to screening. Known history of having Acquired Immunodeficiency Syndrome (AIDS) or positive pre-study result of infection with Human Immunodeficiency Virus (HIV); history or positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. Pregnant or breast feeding. Women of child-bearing potential not using an effective birth control method. Women of child-bearing potential are defined as women physiologically capable of becoming pregnant, UNLESS they meet the following criteria: Post-menopausal: 12 months of natural (spontaneous) amenorrhea or less than 12 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels > 40IU/L, OR; 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy, OR; Using one or more of the following acceptable methods of contraception: surgical sterilization (e.g. bilateral tubal ligation), hormonal contraception (e.g. implantable, injectable, vaginal patch, and oral), and double-barrier methods. Reliable contraception should be maintained throughout the study and for 7 days after study discontinuation. Known or suspected hypersensitivity to any ingredient of study drug(s). Donated blood or lost more than 150 mL of blood within 3 months prior to randomization or plans to donate blood or plasma within 4 weeks after completion of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cilostazol 100 mg<br> | Drug: Cilostazol 100 mg<br>* One immediately-release tablet (Cilostazol 100 mg) at 08:00 and another at 20:00, twice daily oral dose (total daily dose of 200 mg)<br>|
| Experimental: PMR 150 mg<br> | Drug: PMR 150 mg<br>* Two extended-release tablets (PMR 150 mg) at 08:00, single oral dose (total daily dose of 300 mg)<br>|
| Experimental: PMR 200 mg<br> | Drug: PMR 200 mg<br>* Two extended-release tablets (PMR 200 mg/tablet) at 08:00, single oral dose (total daily dose of 400 mg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve, from time zero to last measureable time point (AUC (0-t)) |  | 0-72 hours after morning dose | 
| AUC from time zero to infinity (AUC (0-∞)) |  | 0-72 hours after morning dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral Artery Disease, Cilostazol, PMR, Extended-Release Tablet of Cilostazol