Clinical trial NCT01406002: To Evaluate if Multiple Doses of Rifampicin Change the Blood Concentration of YM150 (Darexaban)
Official title: An Open-label, One-sequence Study to Evaluate the Effect of Multiple Doses of Rifampicin on the Pharmacokinetics of YM150 (Darexaban) and Metabolites in Young Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics of Darexaban and Metabolites
Healthy Subjects
Keywords: Pharmacokinetics
darexaban
YM150
rifampicin
Phase 1
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2011-07-29
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: The primary objective of this study is to determine the effect of rifampicin on the way the body handles darexaban and its metabolites (drug degradation products). The secondary objective of the study is to evaluate the safety and tolerability of a single dose of darexaban alone and when administered together with rifampicin.

Detailed description: This is an open-label, 1-sequence study in young healthy male subjects to evaluate the effect of multiple daily doses of rifampicin on the PK of darexaban and metabolites after a single dose of darexaban. In addition, safety and tolerability of darexaban administered alone and in combination with rifampicin is evaluated. Eligible subjects are admitted to the clinical unit in the morning of Day -1.

Subjects receive a single dose of darexaban on Day 1. Subjects then receive rifampicin once daily (qd) on Days 4-14.On Day 11, the second single dose of darexaban is given in combination with rifampicin.

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 rifampicin or any components of the formulation used
* Any of the liver function tests (i.e. ALT and AST) 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 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
* 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 Donation of blood or blood products within 3 months prior to admission to the Clinical Unit
* 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: Pharmacokinetics of darexaban and its metabolites assessed by plasma concentration
timeFrame: Plasma samples are taken until 72 hours after darexaban dosing
Secondary outcomes:
measure: Monitoring of safety and tolerability through assessment of vital signs, ECG, clinical safety laboratory and adverse events
timeFrame: 15 days
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: Prinicpal Investigator
role: PRINCIPAL_INVESTIGATOR
References:
citation: Groenendaal D, Strabach G, Garcia-Hernandez A, Kadokura T, Heeringa M, Mol R, Eltink C, Onkels H. The pharmacokinetics of darexaban are not affected to a clinically relevant degree by rifampicin, a strong inducer of P-glycoprotein and CYP3A4. Br J Clin Pharmacol. 2013 Feb;75(2):440-9. doi: 10.1111/j.1365-2125.2012.04346.x.