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

Astellas

Status and phase

Completed

Phase 1

Conditions

Healthy Subjects

Pharmacokinetics of Darexaban and Metabolites

Treatments

Drug: ketoconazole

Drug: darexaban

Study type

Interventional

Funder types

Industry

Identifiers

NCT01405989

150-CL-037

2009-015761-32 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

26 patients

Sex

Male

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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