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

NCT ID: NCT01405989

Last Updated: 2014-03-05

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 ketoconazole on the blood concentrations of 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 ketoconazole.

Detailed Description

This is an open-label, 2-period crossover study in young healthy male subjects to evaluate the effect of multiple once daily doses of ketoconazole on the pharmacokinetics (PK) of darexaban and metabolites after a single dose of darexaban. In addition, safety and tolerability of darexaban administered alone and in combination with ketoconazole, is evaluated. Eligible subjects are admitted to the clinical unit in the morning of Day -1. The subjects are randomized to receive either first darexaban plus ketaconazole and then darexaban alone, or first darexaban alone followed by darexaban plus ketoconazole.

Conditions

Pharmacokinetics of Darexaban and Metabolites; Healthy Subjects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: NONE

Study Groups

Treatment arm A

darexaban, wash-out, ketoconazole + darexaban

Group Type: EXPERIMENTAL

darexaban

Intervention Type: DRUG

oral

ketoconazole

Intervention Type: DRUG

oral

Treatment arm B

ketoconazole + darexaban, wash-out, darexaban

Group Type: EXPERIMENTAL

darexaban

Intervention Type: DRUG

oral

ketoconazole

Intervention Type: DRUG

oral

Interventions

darexaban

oral

Intervention Type: DRUG

ketoconazole

oral

Intervention Type: DRUG

Other Intervention Names

YM150; Nizoral

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 ketoconazole 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

• 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

Astellas Pharma Europe

Principal Investigators

Clinical Study Manager

Role: STUDY_CHAIR

Astellas Pharma Europe B.V.

Principal Investigator

Role: PRINCIPAL_INVESTIGATOR

SGS Aster, Paris, France

Locations

SGS Aster

Paris, , France

Countries

France

Other Identifiers

2009-015761-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

150-CL-037

Identifier Type: -

Identifier Source: org_study_id