CompletedNCT02554721CiloMecTUpdated Oct 13, 2021Results posted

Pharmacodynamic Study of Cilostazol in Healthy Volunteers

A Phase 1 interventional study of Cilostazol and Acetylsalicylic acid in Healthy, sponsored by Otsuka Pharmaceutical Co., Ltd.. Completed at 1 site in Germany. Open to male participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-10-13.

Sponsored by Otsuka Pharmaceutical Co., Ltd. (part of Otsuka Holdings Co., Ltd.) · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 77
Allocation: Randomized
Ages: 18 Years to 45 Years
Sex: Male

Study 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.

Conditions studied

Healthy

Keywords

Healthy Volunteers

In context

Lead sponsor

Otsuka Pharmaceutical Co., Ltd. is the lead sponsor of 143 studies on the registry; 11 are open to participants now.

Browse Otsuka Pharmaceutical Co., Ltd. studies →All Otsuka Holdings Co., Ltd. studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 45 Years
Sexes eligible: Male
Accepts healthy volunteers: Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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 design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 77 participants (actual)

Study arms

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: Cilostazol · Drug: Clopidogrel
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: Cilostazol · Drug: Clopidogrel
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: Cilostazol · Drug: Clopidogrel

Interventions

What researchers measure

Primary outcomes

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.
Time frame: Baseline, Visit 5 (Day 22-29)

Secondary outcomes

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.
Time frame: Visit 5 (Day 22-29)

Results

Posted Oct 13, 2021

Participant flow

Participant flow — Overall Study
Milestone	Group 1 (CYP2C19 EM)	Group 2 (CYP2C19 EM)	Group 3 (CYP2C19 IM)	Group 4 CYP2C19 PM)	Not Assigned
Started	20	19	19	17	2
Completed	19	19	19	17	0
Not completed	1	0	0	0	2
Withdrew: Adverse event	1	0	0	0	1
Withdrew: Noncompliance	0	0	0	0	1

Outcome measures

PrimaryEx-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.

Time frame:: Baseline, Visit 5 (Day 22-29)
Reported as:: Geometric mean · ratio

Ex-vivo Inhibition Of Platelet Aggregation (IPA)
ratio	Acetylsalicylic Acid - Cilostazol	Clopidogrel - Cilostazol
5 µM ADP	0.82 (0.5 to 1.37)	1.21 (1.09 to 1.35)
500 mg/L AA	1.03 (1.01 to 1.05)	4.42 (3.42 to 5.73)

SecondaryEffects 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.

Time frame:: Visit 5 (Day 22-29)
Reported as:: Geometric mean · ratio

Effects On Skin Bleeding Time (BT)
ratio	Acetylsalicylic Acid - Cilostazol	Clopidogrel - Cilostazol
Effects On Skin Bleeding Time (BT)	1.31 (1.05 to 1.63)	1.27 (1.09 to 1.48)

Adverse events

Collected over Treatment-emergent adverse events were collected from Day 1 to Day 29. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cilostazol	0/77 (0%)	0/77 (0%)	62/77 (80.5%)
Acetylsalicylic Acid	0/20 (0%)	0/20 (0%)	3/20 (15%)
Clopidogrel	0/55 (0%)	0/55 (0%)	3/55 (5.5%)
Acetylsalicylic Acid - Cilostazol	0/20 (0%)	0/20 (0%)	10/20 (50%)
Clopidogrel - Cilostazol	0/55 (0%)	0/55 (0%)	41/55 (74.5%)

Most frequent other events

Most frequent other events
Event	Cilostazol	Acetylsalicylic Acid	Clopidogrel	Acetylsalicylic Acid - Cilostazol	Clopidogrel - Cilostazol
HeadacheNervous system disorders	60/77	1/20	2/55	10/20	38/55
PalpitationsCardiac disorders	5/77	0/20	0/55	2/20	3/55
Abdominal painGastrointestinal disorders	0/77	2/20	0/55	0/20	0/55
NasopharyngitisInfections and infestations	2/77	0/20	1/55	0/20	3/55

Baseline characteristics

Safety Analysis Set: All subjects who received at least 1 dose of trial medication

Age, Continuous
Age, Continuous(years)	Group 1 (CYP2C19 EM)	Group 2 (CYP2C19 EM)	Group 3 (CYP2C19 IM)	Group 4 CYP2C19 PM)	Not Assigned	Total
Mean	25.8 ± 4.3	28.3 ± 6.5	25.9 ± 4.6	24.2 ± 4.0	26.5 ± 4.9	26.1 ± 5.0

Sex: Female, Male
Sex: Female, Male(Participants)	Group 1 (CYP2C19 EM)	Group 2 (CYP2C19 EM)	Group 3 (CYP2C19 IM)	Group 4 CYP2C19 PM)	Not Assigned	Total
Female	0	0	0	0	0	0
Male	20	19	19	17	2	77

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Group 1 (CYP2C19 EM)	Group 2 (CYP2C19 EM)	Group 3 (CYP2C19 IM)	Group 4 CYP2C19 PM)	Not Assigned	Total
White	20	19	19	17	2	77

Region of Enrollment
Region of Enrollment(Participants)	Group 1 (CYP2C19 EM)	Group 2 (CYP2C19 EM)	Group 3 (CYP2C19 IM)	Group 4 CYP2C19 PM)	Not Assigned	Total
Germany	20	19	19	17	2	77

Study locations

1 site

Bad Krozingen, Germany

References and documents

Study documents

Study protocol · Mar 7, 2018
Statistical analysis plan · May 9, 2018

Documents are hosted by the registry — open the source record to download them.

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reached

Ran from Aug 2015 to primary completion in Mar 2018, 31 months.

Results were first posted in Oct 2021, 3 years 6 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Sep 15, 2015
First posted: Sep 18, 2015
StartActual: Aug 2015
Primary completionActual: Mar 30, 2018
CompletionActual: Mar 30, 2018
Results first posted: Oct 13, 2021
Last update: Oct 13, 2021

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Oct 13, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02554721
Lead sponsor: Otsuka Pharmaceutical Co., Ltd.
Responsible party: Sponsor
First posted: Sep 18, 2015
Start date: Aug 2015
Primary completion: Mar 30, 2018
Completion: Mar 30, 2018
Results posted: Oct 13, 2021
Last update: Oct 13, 2021

Study contacts

Osamu Sato

study director · Otsuka Pharmaceutical Co., Ltd.

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.

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