To Evaluate Whether Acetyl Salicylic Acid (Aspirin) and Darexaban (YM150) Interact in Their Effects

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate whether ASA 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.

Official Title
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A Randomized, Open Label, Three-way Crossover Study to Evaluate the Pharmacodynamic Interactions Between Darexaban (YM150)/Darexaban Glucuronide (YM-222714) and Acetyl Salicylic Acid (ASA) in Healthy Male Subjects

Conditions
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Pharmacodynamic and Pharmacokinetic Interaction, Healthy Subjects

Intervention / Treatment
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* Drug: Darexaban
* Drug: Acetyl Salicylic Acid (ASA)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm 1<br>darexaban, wash-out, ASA, wash-out, darexaban plus ASA | Drug: Darexaban<br>* oral<br>* Other names: YM150;Drug: Acetyl Salicylic Acid (ASA)<br>* oral<br>* Other names: Aspirin;|
| Experimental: Treatment arm 2<br>darexaban, wash-out, darexaban plus ASA, wash-out, ASA | Drug: Darexaban<br>* oral<br>* Other names: YM150;Drug: Acetyl Salicylic Acid (ASA)<br>* oral<br>* Other names: Aspirin;|
| Experimental: Treatment arm 3<br>ASA, wash-out, darexaban, wash-out, darexaban plus ASA | Drug: Darexaban<br>* oral<br>* Other names: YM150;Drug: Acetyl Salicylic Acid (ASA)<br>* oral<br>* Other names: Aspirin;|
| Experimental: Treatment arm 4<br>ASA, wash-out, darexaban plus ASA, wash-out, darexaban | Drug: Darexaban<br>* oral<br>* Other names: YM150;Drug: Acetyl Salicylic Acid (ASA)<br>* oral<br>* Other names: Aspirin;|
| Experimental: Treatment arm 5<br>darexaban plus ASA, wash-out, darexaban, wash-out, ASA | Drug: Darexaban<br>* oral<br>* Other names: YM150;Drug: Acetyl Salicylic Acid (ASA)<br>* oral<br>* Other names: Aspirin;|
| Experimental: Treatment arm 6<br>darexaban plus ASA, wash-out, ASA, wash-out, darexaban | Drug: Darexaban<br>* oral<br>* Other names: YM150;Drug: Acetyl Salicylic Acid (ASA)<br>* oral<br>* Other names: Aspirin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite assessment of pharmacodynamics of darexaban and darexaban glucuronide | Assessment includes skin bleeding time, factor Xa, platelet aggregation, thromboxane B2 synthesis, PT & aPTT | Baseline and after six days of dosing of darexaban, ASA, or a combination of the two | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of darexaban and darexaban glucuronide assessed by plasma concentration |  | Plasma samples are taken until 24 hours after six days of dosing of darexaban, or the combination with ASA | 
| Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG), clinical safety laboratory and adverse events |  | 6 days for each of the 3 treatment periods | 
| Pharmacokinetics of ASA assessed by plasma concentration |  | Plasma samples are taken until 2 hours after six days of dosing of ASA, or the combination with darexaban | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacodynamics, pharmacokinetics, darexaban, Acetyl Salicylic Acid, darexaban glucuronide, YM150, YM-222714, Phase 1