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

Study Overview
=================
Brief Summary
-----------------
The study is designed to evaluate the bioequivalence and the within-subject variability between the test formulation 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
-----------------
An Open-Label, Randomized, Two-Treatment, Two-Sequence, Four-Period, Fully Replicated Crossover Bioequivalence Study of Once Daily PMR Compared to Twice Daily Cilostazol IR Tablets in Healthy Volunteers

Conditions
-----------------
Intermittent Claudication

Intervention / Treatment
-----------------
* Drug: Cilostazol Tablet 100 mg
* Drug: PMR Tablet 145 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must be 18 to 50 years of age, inclusive, at screening. Absence of diseases that could affect the study outcomes. Having a body mass index (BMI) between 18.5 and 29.9 kg/m², inclusive, at screening. Women of child-bearing potential must have a negative serum pregnancy test at screening. Understanding and willing to participate in the clinical study and able to comply with study procedures and visits. Exclusion Criteria: History of bleeding tendency. Use of anticoagulant agent(s) within one (1) month prior to screening. Use of tobacco or nicotine products within two (2) weeks of screening. Intake of over the counter (OTC) or prescription drugs (other than hormonal contraceptives) within two (2) weeks prior to randomization. On any investigational drug(s) or therapeutic device(s) within thirty (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 one (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); known history or positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within three (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 twelve (12) months of spontaneous amenorrhea prior to screening or with serum Follicle Stimulating Hormone (FSH) levels > 40IU/L, OR; Twelve (12) weeks post-surgical bilateral oophorectomy with or without hysterectomy at time of screening, OR; Total hysterectomy with absence of menstrual bleeding for a least 3 months prior to screening. Acceptable birth control methods are bilateral tubal ligation at least three (3) months prior to screening; copper intrauterine device (paragard) or hormonal intrauterine device in place for at least three (3) months prior to screening and remaining in place until the final study visit; Implantable or Injectable contraceptives in place at least three (3) months prior to screening and remaining in place until the final study visit; Combination hormonal oral contraceptive or contraceptive patch in place three (3) months prior to screening and remaining in place until the final study visit. Known or suspected hypersensitivity to any ingredient of the study drug(s). Donated blood or lost more than 450 mL of blood within three (3) months prior to randomization or plans to donate blood or plasma within four (4) weeks after completion of the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment RTRT (R: Cilostazol, T: PMR)<br>Treatment R: One Cilostazol Tablet 100 mg in the morning and another at an interval of 12 hours of the morning dose Treatment T: Two PMR Tablet 145 mg in the morning Four-period dosing following the sequence of Treatment RTRT | Drug: Cilostazol Tablet 100 mg<br>* Two oral doses (total daily dose of 200 mg)<br>* Other names: Treatment R;Drug: PMR Tablet 145 mg<br>* Single oral dose (total daily dose of 290 mg)<br>* Other names: Treatment T;|
| Other: Treatment TRTR (T: PMR, R: Cilostazol)<br>Treatment R: One Cilostazol Tablet 100 mg in the morning and another at an interval of 12 hours of the morning dose Treatment T: Two PMR Tablet 145 mg in the morning Four-period dosing following the sequence of Treatment TRTR | Drug: Cilostazol Tablet 100 mg<br>* Two oral doses (total daily dose of 200 mg)<br>* Other names: Treatment R;Drug: PMR Tablet 145 mg<br>* Single oral dose (total daily dose of 290 mg)<br>* Other names: Treatment T;|

What is the study measuring?
-----------------
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
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Peripheral Artery Disease, Cilostazol, PMR, Extended-Release Tablet of Cilostazol