Pharmacodynamic Study of Cilostazol in Healthy Volunteers

Study Overview
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Brief Summary
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The primary objective of this study is to investigate the effects of Cilostazol, Acetylsalycylic acid and Clopidogrel alone as well as combinations of Cilostazol/Acetylsalicylic acid and Cilostazol/ Clopidogrel on ex-vivo Platelet Function (PF) testing.

Official Title
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Effect of Cilostazol as an add-on Treatment to a Single Antiplatelet Agent (Acetylsalicylic Acid or Clopidogrel) on Platelet Function Testing and Bleeding Time in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Cilostazol
* Drug: Acetylsalicylic acid
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Caucasian male subjects Able to read, to write and to fully understand German language Provision of written informed consent before screening and baseline BMI between 19.0 and 30.0 kg/m2, inclusive and body weight between 50.0 and 100.0 kg, inclusive Good general health as determined by the investigator by medical history, physical examination, vital signs, electrocardiogram, baseline and safety lab Exclusion Criteria: Personal or family history of bleeding disorders, or reasonable suspicion of vascular malformations, including aneurysms Known predisposition to bleeding (e.g. active peptic ulceration, recent (within 6 month) haemorrhagic stroke, proliferative diabetic retinopathy, poorly controlled hypertension) Use of antibiotics within thirty (30) days prior to screening and until baseline visit Clinically significant abnormalities in medical history, physical examination, vital signs, electrocardiogram, baseline and safety lab Supine pulse rate > 100 beats/min or <50 beats/min Systolic blood pressure <100 or >140 mmHg Diastolic blood pressure <50 or >90 mmHg Concomitant use of any other medication including over-the-counter preparations

Ages Eligible for Study
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Minimum Age: 18 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: Group 1 (CYP2C19 Wild Type)<br>Trial period A: Cilostazol 100 mg twice daily for 1 week (Days 1-7) Trial period B: Wash out period (Days 8-14) Trial period C: Acetylsalicylic acid 100 mg once daily for 1 week (Days 15-21) Trial period D: Cilostazol 100 mg twice daily and Acetylsalicylic acid 100mg once daily for 1 week (Days 22-28) | Drug: Cilostazol<br> <br> Drug: Acetylsalicylic acid<br> <br> |
| Experimental: Group 2 (CYP2C19 Wild Type)<br>Trial period A: Cilostazol 100 mg twice daily for 1 week (Days 1-7) Trial period B: Wash out period (Days 8-14) Trial period C: Clopidogrel 75 mg once daily for 1 week (Days 15-21) Trial period D: Cilostazol 100 mg twice daily and Clopidogrel 75 mg once daily for 1 week (Days 22-28) | Drug: Cilostazol<br> <br> Drug: Clopidogrel<br> <br> |
| Experimental: Group 3 (CYP2C19 heterozygous (*1/*2) )<br>Trial period A: Cilostazol 100 mg twice daily for 1 week (Days 1-7) Trial period B: Wash out period (Days 8-14) Trial period C: Clopidogrel 75 mg once daily for 1 week (Days 15-21) Trial period D: Cilostazol 100 mg twice daily and Clopidogrel 75 mg once daily for 1 week (Days 22-28) | Drug: Cilostazol<br> <br> Drug: Clopidogrel<br> <br> |
| Experimental: Group 4 (CYP2C19 homozygous (*2/*2))<br>Trial period A: Cilostazol 100 mg twice daily for 1 week (Days 1-7) Trial period B: Wash out period (Days 8-14) Trial period C: Clopidogrel 75 mg once daily for 1 week (Days 15-21) Trial period D: Cilostazol 100 mg twice daily and Clopidogrel 75 mg once daily for 1 week (Days 22-28) | Drug: Cilostazol<br> <br> Drug: Clopidogrel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ex-vivo Inhibition Of Platelet Aggregation (IPA) | The effect of ASA in combination with cilostazol and clopidogrel in combination with cilostazol on IPA was determined ex vivo in citrated platelet rich plasma (PRP) after stimulation of aggregation by low-level adenosine diphosphate (ADP) (5 micromolar [uM]) and arachidonic acid (AA) (500 milligrams/liter [mg/L]). Light transmission aggregometry (LTA) was used to measure residual aggregation (the percentage of aggregation 5 minutes after the addition of ADP or AA). Results are reported as the 95% confidence intervals for the reported geometric mean ratios (GMRs) ([cilostazol+reference (ASA or clopidogrel)]/reference) for IPA. | Baseline, Visit 5 (Day 22-29) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects On Skin Bleeding Time (BT) | The effect of ASA in combination with cilostazol and clopidogrel in combination with cilostazol on skin BT (minutes) was determined with the Ivy method, utilizing standardized bleeding with the Surgicutt device. Results include the 95% confidence intervals for the reported GMRs ([cilostazol+reference]/reference) for skin BT. | Visit 5 (Day 22-29) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteers