Drug Interaction Study of Isavuconazole and Warfarin in Healthy Male Subjects

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01657825
• Other study ID #: 9766-CL-0033
• Status: Completed
• Phase: Phase 1
• First received: August 2, 2012
• Last updated: August 27, 2012
• Start date: June 2012
• Est. completion date: July 2012

Study information

• Verified date: August 2012
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

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

Intervention

Drug:
• Isavuconazole
oral
• Warfarin
oral

Locations

Country	Name	City	State
United States	Spaulding Clinical	West Bend	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	Basilea Pharmaceutica International Ltd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of Pharmacokinetic (PK) variables for S-warfarin (in plasma): AUCinf, AUClast, Cmax	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)	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	No
Secondary	Composite of PK variables for R-warfarin (in plasma): AUCinf, AUClast, Cmax		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	No
Secondary	Composite of Pharmacokinetic (PK) variables for S-warfarin and R-warfarin (in plasma): tmax, Vz /F, CL/F, and t1/2	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)	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	No
Secondary	PK variable for isavuconazole (in plasma): trough concentration (Ctrough)		Days 18-20 and Days 22-27, predose and Day 28 predose and 24 hours post dose	No
Secondary	Composite of PK variable for isavuconazole (in plasma): AUCtau , Cmax, and tmax	AUC during the time interval between consecutive dosing (AUCtau)	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	No
Secondary	Pharmacodynamic Variables: MAXINR, AUCINR, MAXPT, and AUCPT	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)	Day 1 and Day 20 predose and at 6, 12, 24, 48, 72, 96, 168, and 216 hours post-warfarin-dose	No
Secondary	Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) physical examinations, and vital signs		Day 1 through Day 29, Day 35 ± 2	No