Drug Interaction Study of Isavuconazole and Warfarin in Healthy Male Subjects

• ClinicalTrials.gov Identifier: NCT01657825
• Recruitment Status: Completed
• First Posted: August 6, 2012
• Last Update Posted: August 28, 2012
• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborator: Basilea Pharmaceutica International Ltd
• Information provided by (Responsible Party): Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information

• First Submitted Date: August 2, 2012
• First Posted Date: August 6, 2012
• Last Update Posted Date: August 28, 2012
• Study Start Date: June 2012
• Actual Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 2, 2012)

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 ]

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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 2, 2012)

• 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 ]
• 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 ]
  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 ]
• 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 ]
  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 ]
  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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Drug Interaction Study of Isavuconazole and Warfarin in Healthy Male Subjects
• Official Title: 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
• Brief Summary: 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.

Detailed Description

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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label)

Condition

• Pharmacokinetics of Isavuconazole
• Pharmacokinetics of S- and R-warfarin
• Pharmacodynamics of Warfarin
• Healthy Volunteers

Intervention

• Drug: Isavuconazole
  oral
  Other Name: BAL8557
• Drug: Warfarin
  oral
  Other Name: Coumadin

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 2, 2012): 20
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: July 2012
• Actual Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01657825
• Other Study ID Numbers: 9766-CL-0033
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
• Study Sponsor: Astellas Pharma Global Development, Inc.
• Collaborators: Basilea Pharmaceutica International Ltd

Investigators

• Study Director: Medical Director; Astellas Pharma Global Development

• PRS Account: Astellas Pharma Inc
• Verification Date: August 2012