Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Drug Interaction Study of Isavuconazole and Warfarin in Healthy Male Subjects

This study has been completed.
Sponsor:
Collaborator:
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier:
NCT01657825
First received: August 2, 2012
Last updated: August 27, 2012
Last verified: August 2012

August 2, 2012
August 27, 2012
June 2012
July 2012   (final data collection date for primary outcome measure)
Composite of Pharmacokinetic (PK) variables for S-warfarin (in plasma): AUCinf, AUClast, Cmax [ Time Frame: Days 1 and 20, predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12,16, 24, 48, 72, 96, 120, 144, 168, and 216 hours postdose ] [ Designated as safety issue: No ]
Area under the curve (AUC) from time 0 extrapolated to infinity (AUCinf), AUC from time of dosing to last quantifiable concentration (AUClast ), and maximum concentration (Cmax)
Same as current
Complete list of historical versions of study NCT01657825 on ClinicalTrials.gov Archive Site
  • Composite of PK variables for R-warfarin (in plasma): AUCinf, AUClast, Cmax [ Time Frame: Days 1 and 20, predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12,16, 24, 48, 72, 96, 120, 144, 168, and 216 hours postdose ] [ Designated as safety issue: No ]
  • Composite of Pharmacokinetic (PK) variables for S-warfarin and R-warfarin (in plasma): tmax, Vz /F, CL/F, and t1/2 [ Time Frame: Days 1 and 20, predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12,16, 24, 48, 72, 96, 120, 144, 168, and 216 hours postdose ] [ Designated as safety issue: No ]
    Time to attain Cmax (tmax) , apparent volume of distribution (Vz /F), apparent body clearance after oral dosing (CL/F), and apparent terminal elimination half-life (t1/2)
  • PK variable for isavuconazole (in plasma): trough concentration (Ctrough) [ Time Frame: Days 18-20 and Days 22-27, predose and Day 28 predose and 24 hours post dose ] [ Designated as safety issue: No ]
  • Composite of PK variable for isavuconazole (in plasma): AUCtau , Cmax, and tmax [ Time Frame: Day 19 predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 16 hours post dose; and Day 20, predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, and 36 hours postdose ] [ Designated as safety issue: No ]
    AUC during the time interval between consecutive dosing (AUCtau)
  • Pharmacodynamic Variables: MAXINR, AUCINR, MAXPT, and AUCPT [ Time Frame: Day 1 and Day 20 predose and at 6, 12, 24, 48, 72, 96, 168, and 216 hours post-warfarin-dose ] [ Designated as safety issue: No ]
    International Normalized Ratio (INR), Maximum observed change INR value (MAXINR), Area under the INR time curve from 0 to 216 hours (AUCINR), Maximum observed change in prothrombin time (PT)value (MAXPT), Area under the PT time curve from 0 to 216 hours (AUCPT)
  • Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) physical examinations, and vital signs [ Time Frame: Day 1 through Day 29, Day 35 ± 2 ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Drug Interaction Study of Isavuconazole and Warfarin in Healthy Male Subjects
A Phase 1, Open-Label, Sequential Study of the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Warfarin in Healthy Male Subjects

The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics (PK) of warfarin after single dose administration.

Subjects will receive a single dose of warfarin on Day 1 followed by a 15 day wash-out period (time from warfarin dosing to isavuconazole dosing).

On Days 16 and 17, isavuconazole will be dosed three times daily (TID). TID doses will be administered 8 hours apart. On Days 18 through 28, isavuconazole will be administered once daily (QD). All subjects will be administered a single dose of warfarin on Day 20. A follow up visit will occur approximately 7 days after the last dose of isavuconazole. Blood samples for pharmacokinetics will be collected throughout the study.

Interventional
Phase 1
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
  • Pharmacokinetics of Isavuconazole
  • Pharmacokinetics of S- and R-warfarin
  • Pharmacodynamics of Warfarin
  • Healthy Volunteers
  • Drug: Isavuconazole
    oral
    Other Name: BAL8557
  • Drug: Warfarin
    oral
    Other Name: Coumadin
Experimental: Isavuconazole and warfarin
Isavuconazole three times daily (TID) for 2 days followed by once daily (QD) dosing for 11 days and warfarin single doses on Days 1 and 20
Interventions:
  • Drug: Isavuconazole
  • Drug: Warfarin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
July 2012
July 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Subjects must have BMI of 18 to 32 kg/m2 and a body weight of at least 45 kg
  • Subjects must have normal laboratory values especially for ALT, AST, protein C and S, and prothrombin time

Exclusion Criteria:

  • The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia or torsade de pointes, structural heart disease, or family history of Long QT syndrome (suggested by sudden death of a close relative at a young age due to possible or probable cardiac causes)
  • The subject has a positive result for hepatitis C antibodies or hepatitis B surface antigen at Screening or is known to be positive for human immunodeficiency virus (HIV)
  • The subject has a known or suspected allergy to any of the components of the trial products or the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods (as judged by the investigator), or a history of severe anaphylactic reactions
  • The subject is a smoker (any use of tobacco or nicotine containing products) within 6 months prior to Screening
  • The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Day -1, or over-the-counter medications within 1 week prior to Day -1
  • The subject has received an experimental agent within 30 days or 5 half-lives, whichever is longer prior to Day -1
  • The subject has a recent history (within the last 2 years) of drug or alcohol abuse, as defined by the investigator, or a positive drug and/or alcohol screen
Male
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01657825
9766-CL-0033
No
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Astellas Pharma Global Development, Inc.
Basilea Pharmaceutica International Ltd
Study Director: Medical Director Astellas Pharma Global Development
Astellas Pharma Inc
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP