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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Pharmacodynamic and Pharmacokinetic Interaction
• Intervention / Treatment: Drug: Darexaban; Drug: Acetyl Salicylic Acid (ASA)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • SGS Aster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Principal Investigator: Principal Investigator, SGS Aster, Paris, France

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: August 1, 2011
• First Submitted That Met QC Criteria: August 25, 2011
• First Posted (Estimate): August 29, 2011

Study Record Updates

• Last Update Posted (Estimate): August 29, 2011
• Last Update Submitted That Met QC Criteria: August 25, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: pharmacokinetics; Phase 1; Pharmacodynamics; YM150; darexaban; Acetyl Salicylic Acid; darexaban glucuronide; YM-222714
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective 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; Protease Inhibitors; Dermatologic Agents; Antifungal Agents; Keratolytic Agents; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Aspirin; Salicylic Acid; Salicylates; Darexaban
• Other Study ID Numbers: 150-CL-034; 2007-002194-31 (EudraCT Number)