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

Healthy Subjects Clinical Trial

Official title:

An Open-label, Randomized, Two-period Crossover Study to Evaluate the Effect of Multiple Doses of Ketoconazole on the Pharmacokinetics of Darexaban and Metabolites in Young Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01405989
• Other study ID #: 150-CL-037
• Secondary ID: 2009-015761-32
• Status: Completed
• Phase: Phase 1
• First received: July 28, 2011
• Last updated: March 3, 2014
• Start date: January 2010
• Est. completion date: March 2010

Study information

• Verified date: July 2011
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Subjects
• Pharmacokinetics of Darexaban and Metabolites

Intervention

Drug:
• darexaban
oral
• ketoconazole
oral

Locations

Country	Name	City	State
France	SGS Aster	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics of darexaban and its metabolites assessed by plasma concentration		Plasma samples are taken until 72 hours (darexaban alone) or 144 hours (combination of darexaban and ketoconazole) after darexaban dosing	No
Secondary	Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG), clinical safety laboratory and adverse events		16 days	Yes

External Links

•   Link to Results on JAPIC