Clinical trial NCT01409603: To Evaluate Whether Naproxen and Darexaban (YM150) Interact in Their Effects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacodynamic Interaction
Healthy Subjects
Keywords: Pharmacodynamics
darexaban
naproxen
YM150
Phase 1
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2011-08-04
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Assessment of pharmacodynamics of naproxen
timeFrame: Baseline and 3 hours after multiple dosing (darexaban: 6 days, naproxen: 4 days) of darexaban, naproxen, or a combination of the two
Secondary outcomes:
measure: Assessment of pharmacodynamics of darexaban
timeFrame: Baseline and 3 hours after multiple dosing (darexaban: 6 days, naproxen: 4 days) of darexaban, naproxen, or a combination of the two
measure: Pharmacokinetics of darexaban assessed by plasma concentration
timeFrame: Plasma samples are taken until 24 hours after six days of dosing of darexaban, or the combination with naproxen
measure: Pharmacokinetics of naproxen assessed by plasma concentration
timeFrame: Plasma samples are taken until 12 hours after four days of dosing of naproxen, or the combination with darexaban
measure: Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG), clinical safety laboratory and adverse events
timeFrame: 6 days (for treatment periods with darexaban) or 4 days. (naproxen alone)
Other outcomes:
Locations:
city: Paris
country: France
facility: SGS Aster
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Clinical Study Manager
role: STUDY_CHAIR
affiliation: SGS Aster, Paris, France
name: Principal Investigator
role: PRINCIPAL_INVESTIGATOR
References: