Cilostazol-Simvastatin Drug Interaction Study

Study Overview
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Brief Summary
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This is a randomized, open-label, single & multiple-dose, parallel study to investigate the effect of cilostazol on the disposition of simvastatin & pravastatin in healthy male volunteers

Detailed Description
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Eligibility for participation of this study will be determined from demographic information, medical history, physical examination, electrocardiogram (ECG) and clinical laboratory tests within 4 weeks before study drug administration. Subjects suitable for this study will be admitted to the Clinical Trial Center of Ajou University Medical Center on the day before dosing (Day -1). On Day 1, Subjects will be dosed simvastatin 40 mg or pravastatin 20 mg. Pharmacokinetic samplings and blood pressure/pulse rate measurement will be done upto 24 hours after dosing. From Day 2   7, Subjects will be dosed cilostazol 100 mg twice a day. On Day 8, Subjects will be dosed simvastatin 40 mg or pravastatin 20 mg with cilostazol 100 mg twice a day. Pharmacokinetic samplings and blood pressure/pulse rate measurement will be done upto 24 hours after dosing.

Official Title
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A Randomized, Open-label, Multiple-dose, Parallel Study to Investigate The Effect of Cilostazol on the Disposition of Simvastatin in Healthy Male Volunteers

Conditions
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Dyslipidemias, Peripheral Artery Disease

Intervention / Treatment
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* Drug: Simvastatin
* Drug: Pravastatin
* Drug: Cilostazol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects aged 20 - 45 years With in 20% of ideal body weight, {Ideal body weight=[height(cm)-100]*0.9} Agreement with written informed consent Exclusion Criteria: Clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal disease or mental disorder (Past history or present) Inadequate result of laboratory test (especially, AST/ALT > 1.25 x UNL, Total bilirubin > 1.5 x UNL) Positive reaction in the HBs Ag, anti-HCV Ab, anti-HIV Ab, VDRL test Taking OTC(Over the counter)medicine including oriental medicine within 7 days Clinically significant allergic disease (Except for mild allergic rhinitis and dermatitis seems to be not need for medication) Subject with known for hypersensitivity reaction to Cilostazol, Simvastatin or Pravastatin Previous whole blood donation within 60 days or component blood donation within 30 days Previous participation of other trial within 90 days Continued taking caffeine (caffeine > 5 cup/day), drinking (alcohol > 30 g/day) and severe heavy smoker (cigarette > 1/2 pack per day) An impossible one who participates in clinical trial by investigator's decision including for reason of laboratory test result

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simvastatin+Cilostazol<br>Simvastatin 40 mg on Day 1. Cilostazol 100 mg twice a day for 6 days. Simvastatin 40 mg and Cilostazol 100 mg twice a day on Day 8. | Drug: Simvastatin<br>* Simvastatin 40 mg on Day 1 & Day 8.<br>* Other names: S;Drug: Cilostazol<br>* Cilostazol 100 mg twice a day for 6 days & on Day 8 with statin.<br>* Other names: C;|
| Active Comparator: Pravastatin+Cilostazol<br>Pravastatin 20 mg on Day 1. Cilostazol 100 mg twice a day for 6 days. Pravastatin 20 mg and Cilostazol 100 mg twice a day on Day 8. | Drug: Pravastatin<br>* Pravastatin 20 mg on Day 1 & Day 8.<br>* Other names: P;Drug: Cilostazol<br>* Cilostazol 100 mg twice a day for 6 days & on Day 8 with statin.<br>* Other names: C;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (area under the time-concentration curve) of Simvastatin |  | up to 12 hours after Simvastatin dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum plasma concentration) of Simvastatin |  | up to 12 hours after Simvastatin dosing | 
| Cmax (maximum plasma concentration) of Pravastatin |  | up to 12 hours after Pravastatin dosing | 
| AUC (area under the time-concentration curve) of Pravastatin |  | up to 12 hours after Pravastatin dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug-drug interaction, Pharmacokinetics