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

This study has been completed.
Sponsor:
Information provided by:
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01405989
First received: July 28, 2011
Last updated: NA
Last verified: July 2011
History: No changes posted
  Purpose

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
Endpoint Classification: Pharmacokinetics Study
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:

U.S. FDA Resources

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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: Yes ]

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
oral
Other Name: YM150
Drug: ketoconazole
oral
Other Name: Nizoral
Experimental: Treatment arm B
ketoconazole + darexaban, wash-out, darexaban
 Drug: darexaban
oral
Other Name: YM150
Drug: ketoconazole
oral
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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01405989

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

No publications provided

Responsible Party: Disclosure Office Europe, Astellas Pharma Europe
ClinicalTrials.gov Identifier: NCT01405989     History of Changes
Other Study ID Numbers: 150-CL-037, 2009-015761-32
Study First Received: July 28, 2011
Last Updated: July 28, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Astellas Pharma Inc:
Pharmacokinetics
darexaban
ketoconazole
Phase 1

Additional relevant MeSH terms:
Ketoconazole
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
 Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013