Pharmacodynamic Study of Cilostazol in Healthy Volunteers (CiloMecT)

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Clopidogrel; Drug: Cilostazol; Drug: Acetylsalicylic acid

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Bad Krozingen, Germany

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 (CYP2C19 Wild Type); 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; Drug: Acetylsalicylic acid
Experimental: Group 2 (CYP2C19 Wild Type); 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: Clopidogrel; Drug: Cilostazol
Experimental: Group 3 (CYP2C19 heterozygous (*1/*2) ); 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: Clopidogrel; Drug: Cilostazol
Experimental: Group 4 (CYP2C19 homozygous (*2/*2)); 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: Clopidogrel; Drug: Cilostazol

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): March 30, 2018
• Study Completion (Actual): March 30, 2018

Study Registration Dates

• First Submitted: September 15, 2015
• First Submitted That Met QC Criteria: September 17, 2015
• First Posted (Estimate): September 18, 2015

Study Record Updates

• Last Update Posted (Actual): October 13, 2021
• Last Update Submitted That Met QC Criteria: September 16, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Healthy Volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neuroprotective Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Aspirin; Clopidogrel; Cilostazol
• Other Study ID Numbers: 21-13-102; 2013-002633-38 (EudraCT Number)