To Evaluate Whether Naproxen and Darexaban (YM150) Interact in Their Effects

A Phase I, Open-Label, Randomized 3-Period Crossover Study in Healthy Male Subjects to Evaluate the Pharmacodynamic Interactions Between YM150 on Naproxen at Steady-State

The primary objective of this study is to evaluate whether naproxen 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 Interaction
• Intervention / Treatment: Drug: darexaban; Drug: Naproxen

• Study Type: Interventional
• Enrollment (Actual): 26
• 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: Yes
• 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 naproxen or any components of the formulation used
• A contra-indication for the use of naproxen
• 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 A; darexaban, wash-out, naproxen, wash-out, combination therapy	Drug: darexaban; oral; Other Names: YM150; Drug: Naproxen; oral; Other Names: Naprosyne
Experimental: Treatment arm B; darexaban, wash-out, combination therapy, wash-out, naproxen	Drug: darexaban; oral; Other Names: YM150; Drug: Naproxen; oral; Other Names: Naprosyne
Experimental: Treatment arm C; naproxen, wash-out, darexaban, wash-out, combination therapy	Drug: darexaban; oral; Other Names: YM150; Drug: Naproxen; oral; Other Names: Naprosyne
Experimental: Treatment arm D; naproxen, wash-out, combination therapy, wash-out, darexaban	Drug: darexaban; oral; Other Names: YM150; Drug: Naproxen; oral; Other Names: Naprosyne
Experimental: Treatment arm E; combination therapy, wash-out, naproxen, wash-out, darexaban	Drug: darexaban; oral; Other Names: YM150; Drug: Naproxen; oral; Other Names: Naprosyne
Experimental: Treatment arm F; combination therapy, wash-out, darexaban, wash-out, naproxen	Drug: darexaban; oral; Other Names: YM150; Drug: Naproxen; oral; Other Names: Naprosyne

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assessment of pharmacodynamics of naproxen	Baseline and 3 hours after multiple dosing (darexaban: 6 days, naproxen: 4 days) of darexaban, naproxen, or a combination of the two

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessment of pharmacodynamics of darexaban	Baseline and 3 hours after multiple dosing (darexaban: 6 days, naproxen: 4 days) of darexaban, naproxen, or a combination of the two
Pharmacokinetics of darexaban assessed by plasma concentration	Plasma samples are taken until 24 hours after six days of dosing of darexaban, or the combination with naproxen
Pharmacokinetics of naproxen assessed by plasma concentration	Plasma samples are taken until 12 hours after four days of dosing of naproxen, or the combination with darexaban
Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG), clinical safety laboratory and adverse events	6 days (for treatment periods with darexaban) or 4 days. (naproxen alone)

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Link to Results on JAPIC

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: August 1, 2011
• First Submitted That Met QC Criteria: August 3, 2011
• First Posted (Estimate): August 4, 2011

Study Record Updates

• Last Update Posted (Estimate): April 11, 2013
• Last Update Submitted That Met QC Criteria: April 9, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Phase 1; Pharmacodynamics; naproxen; YM150; darexaban
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Gout Suppressants; Naproxen; Darexaban
• Other Study ID Numbers: 150-CL-039; 2009-015762-64 (EudraCT Number)