To Evaluate if Multiple Doses of Rifampicin Change the Blood Concentration of YM150 (Darexaban)

NCT ID: NCT01406002

Last Updated: 2013-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2010-03-31

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.

Conditions

Pharmacokinetics of Darexaban and Metabolites; Healthy Subjects

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Study Groups

Treatment arm 1

darexaban, wash-out, rifampicin + darexaban

Group Type: EXPERIMENTAL

darexaban

Intervention Type: DRUG

oral

Rifampicin

Intervention Type: DRUG

oral

Interventions

darexaban

oral

Intervention Type: DRUG

Rifampicin

oral

Intervention Type: DRUG

Other Intervention Names

YM150; Rifadin

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Study Manager

Role: STUDY_CHAIR

Astellas Pharma Europe B.V.

Prinicpal Investigator

Role: PRINCIPAL_INVESTIGATOR

SGS Aster, Paris, France

Locations

SGS Aster

Paris, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 22642721 (View on PubMed)

Other Identifiers

2009-015763-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

150-CL-045

Identifier Type: -

Identifier Source: org_study_id