Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study has been completed.
Information provided by:
Astellas Pharma Inc Identifier:
First received: July 28, 2011
Last updated: March 3, 2014
Last verified: July 2011
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 Intervention Phase
Pharmacokinetics of Darexaban and Metabolites
Healthy Subjects
Drug: darexaban
Drug: ketoconazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Astellas Pharma Inc:

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

Enrollment: 26
Study Start Date: January 2010
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: 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
  More Information

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 )
Study First Received: July 28, 2011
Last Updated: March 3, 2014

Keywords provided by Astellas Pharma Inc:
Phase 1

Additional relevant MeSH terms:
Factor Xa Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors processed this record on April 26, 2017