Pharmacodynamic Study of Cilostazol in Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Cilostazol; Drug: Acetylsalicylic acid; Drug: Clopidogrel

• Registration Number: NCT02554721
• Lead Sponsor: Otsuka Pharmaceutical Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-08
• Study First Submitted: 2015-09-15
• Study First Submitted QC: 2015-09-17
• Study First Posted: 2015-09-18
• Primary Completion: 2018-03-30
• Study Completion: 2018-03-30
• Results First Submitted: 2021-08-05
• Status Verified: 2021-09
• Results First Submitted QC: 2021-09-16
• Last Update Submitted: 2021-09-16
• Results First Posted: 2021-10-13
• Last Update Posted: 2021-10-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 77

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 2 (CYP2C19 Wild Type)	Cilostazol	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)
Group 3 (CYP2C19 heterozygous (*1/*2) )	Cilostazol	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)
Group 1 (CYP2C19 Wild Type)	Cilostazol	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)
Group 1 (CYP2C19 Wild Type)	Acetylsalicylic acid	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)
Group 2 (CYP2C19 Wild Type)	Clopidogrel	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)
Group 3 (CYP2C19 heterozygous (*1/*2) )	Clopidogrel	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)
Group 4 (CYP2C19 homozygous (*2/*2))	Clopidogrel	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)
Group 4 (CYP2C19 homozygous (*2/*2))	Cilostazol	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)

Primary Outcome Measures

Name	Time	Method
Ex-vivo Inhibition Of Platelet Aggregation (IPA)	Baseline, Visit 5 (Day 22-29)	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.

Secondary Outcome Measures

Name	Time	Method
Effects On Skin Bleeding Time (BT)	Visit 5 (Day 22-29)	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.