To Evaluate Whether Acetyl Salicylic Acid (Aspirin), the Combination of Aspirin and Clopidogrel and Darexaban (YM150) Interact in Their Effects

Phase 1

Completed

• Conditions: Pharmacodynamic Interaction; Healthy Subjects
• Interventions: Drug: darexaban; Drug: darexaban (double dose); Drug: Acetyl Salicylic Acid; Drug: clopidogrel

• Registration Number: NCT01409616
• Lead Sponsor: Astellas Pharma Inc

Brief Summary

The primary objective of this study is to evaluate whether ASA, the combination of ASA and clopidogrel, and darexaban, which have different effects on blood coagulation, influence each other in their effects. Also it will be investigated whether the blood levels of either drug are influenced by the presence of the other drug. In addition, the safety and tolerability of each drug and the combination of the drugs will be investigated.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-04
• Primary Completion: 2009-09
• Study Completion: 2009-09
• Status Verified: 2011-08
• Study First Submitted: 2011-08-01
• Study First Submitted QC: 2011-08-03
• Study First Posted: 2011-08-04
• Last Update Submitted: 2013-03-19
• Last Update Posted: 2013-03-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 100

Inclusion Criteria

• Body mass index (BMI) between 18.5-30.0 kg/m2
• Male subjects must be non-fertile, i.e. surgically sterilized or must practice an adequate contraceptive method to prevent pregnancies

Exclusion Criteria

• Known or suspected hypersensitivity to darexaban or ASA or any components of the formulation used
• Any of the liver function tests (i.e. ALT, AST and bilirubin) above the upper limit of normal at repeated measures
• Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic as judged by the medical investigator
• Any clinically significant abnormality following the investigator's review of the pre-study physical examination, ECG and clinical laboratory tests
• Use of any prescribed or OTC (over-the-counter) drugs (including vitamins, natural and herbal remedies, e.g. St. John's wort) in the 2 weeks prior to admission to the Clinical Unit, except for occasional use of paracetamol (up to 3 g/day)
• Regular use of any inducer of liver metabolism (e.g. barbiturates, rifampicin) in the 3 months prior to admission to the Clinical Unit.
• Donation of blood or blood products within 3 months prior to admission to the Clinical Unit
• Any use of drugs of abuse, or smoking of more than 10 cigarettes (or equivalent) or more than 21 units (210 g) of alcohol per week within the 3 months prior to study
• Participation in any clinical study within 3 months or participation in more than 3 clinical studies within 12 months, prior to the expected date of enrolment into the study, provided that the clinical study did not entail a biological compound with a long terminal half life

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment arm B	darexaban	ASA + darexaban, w.o., ASA
Treatment arm B	Acetyl Salicylic Acid	ASA + darexaban, w.o., ASA
Treatment arm C	Acetyl Salicylic Acid	ASA, w.o., darexaban (double dose) + ASA
Treatment arm D	darexaban (double dose)	darexaban (double dose) + ASA, w.o., ASA
Treatment arm D	Acetyl Salicylic Acid	darexaban (double dose) + ASA, w.o., ASA
Treatment arm E	Acetyl Salicylic Acid	ASA + clopidogrel, w.o., ASA + clopidogrel + darexaban
Treatment arm F	darexaban	ASA + clopidogrel + darexaban, w.o., ASA + clopidogrel
Treatment arm A	Acetyl Salicylic Acid	ASA, wash-out (w.o.), ASA + darexaban
Treatment arm F	Acetyl Salicylic Acid	ASA + clopidogrel + darexaban, w.o., ASA + clopidogrel
Treatment arm F	clopidogrel	ASA + clopidogrel + darexaban, w.o., ASA + clopidogrel
Treatment arm G	Acetyl Salicylic Acid	ASA + clopidogrel, w.o., darexaban (double dose) + ASA + clopidogrel
Treatment arm G	darexaban (double dose)	ASA + clopidogrel, w.o., darexaban (double dose) + ASA + clopidogrel
Treatment arm G	clopidogrel	ASA + clopidogrel, w.o., darexaban (double dose) + ASA + clopidogrel
Treatment arm H	Acetyl Salicylic Acid	darexaban (double dose) + ASA + clopidogrel, w.o., ASA + clopidogrel
Treatment arm H	clopidogrel	darexaban (double dose) + ASA + clopidogrel, w.o., ASA + clopidogrel
Treatment arm C	darexaban (double dose)	ASA, w.o., darexaban (double dose) + ASA
Treatment arm H	darexaban (double dose)	darexaban (double dose) + ASA + clopidogrel, w.o., ASA + clopidogrel
Treatment arm E	clopidogrel	ASA + clopidogrel, w.o., ASA + clopidogrel + darexaban
Treatment arm A	darexaban	ASA, wash-out (w.o.), ASA + darexaban
Treatment arm E	darexaban	ASA + clopidogrel, w.o., ASA + clopidogrel + darexaban

Primary Outcome Measures

Name	Time	Method
Assessment of pharmacodynamics of darexaban	Baseline and up to 24 hours after six days of dosing of darexaban, ASA, clopidogrel, or a combination

Secondary Outcome Measures

Name	Time	Method
Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG), clinical safety laboratory and adverse events	6 days for each of the 2 treatment periods
Assessment of pharmacodynamics of ASA and a combination of ASA and clopidogrel	Baseline and up to 24 hours after six days of dosing of darexaban, ASA, clopidogrel, or a combination
Pharmacokinetics of ASA and the combination of ASA and clopidogrel assessed by plasma concentration	Plasma samples are taken until 24 hours after six days of dosing of ASA, a combination of ASA and clopidogrel, or the combination with darexaban

Trial Locations

Locations (1)

SGS Aster; 🇫🇷 Paris, France