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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01405989
Recruitment Status : Completed
First Posted : July 29, 2011
Last Update Posted : March 5, 2014
Information provided by:
Astellas Pharma Inc

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.

Condition or disease Intervention/treatment Phase
Pharmacokinetics of Darexaban and Metabolites Healthy Subjects Drug: darexaban Drug: ketoconazole Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
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
Study Start Date : January 2010
Actual Primary Completion Date : March 2010
Actual Study Completion Date : March 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Treatment arm A
darexaban, wash-out, ketoconazole + darexaban
Drug: darexaban
Other Name: YM150
Drug: ketoconazole
Other Name: Nizoral
Experimental: Treatment arm B
ketoconazole + darexaban, wash-out, darexaban
Drug: darexaban
Other Name: YM150
Drug: ketoconazole
Other Name: Nizoral

Primary Outcome Measures :
  1. Pharmacokinetics of darexaban and its metabolites assessed by plasma concentration [ Time Frame: Plasma samples are taken until 72 hours (darexaban alone) or 144 hours (combination of darexaban and ketoconazole) after darexaban dosing ]

Secondary Outcome Measures :
  1. Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG), clinical safety laboratory and adverse events [ Time Frame: 16 days ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01405989

SGS Aster
Paris, France, 75015
Sponsors and Collaborators
Astellas Pharma Inc
Study Chair: Clinical Study Manager Astellas Pharma Europe B.V.
Principal Investigator: Principal Investigator SGS Aster, Paris, France

Additional Information:
Responsible Party: Disclosure Office Europe, Astellas Pharma Europe Identifier: NCT01405989     History of Changes
Other Study ID Numbers: 150-CL-037
2009-015761-32 ( EudraCT Number )
First Posted: July 29, 2011    Key Record Dates
Last Update Posted: March 5, 2014
Last Verified: July 2011

Keywords provided by Astellas Pharma Inc:
Phase 1

Additional relevant MeSH terms:
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Factor Xa Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors