Drug Interaction Study of Isavuconazole and Warfarin in Healthy Male Subjects

NCT01657825 | Completed Phase 1

• 1 other identifier: 9766-CL-0033
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

isavuconazole; warfarin; Healthy Volunteers; BAL8557; Coumadin

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• 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

• Composite of Pharmacokinetic (PK) variables for S-warfarin and R-warfarin (in plasma): tmax, Vz /F, CL/F, and 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

• 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

• Composite of PK variable for isavuconazole (in plasma): AUCtau , Cmax, and tmax

  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

• Pharmacodynamic Variables: MAXINR, AUCINR, MAXPT, and AUCPT

  Day 1 and Day 20 predose and at 6, 12, 24, 48, 72, 96, 168, and 216 hours post-warfarin-dose

Study Arms (1)

Isavuconazole and warfarin

EXPERIMENTAL

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

Drug: Isavuconazole; Drug: Warfarin

Interventions

Isavuconazole DRUG

oral

Also known as: BAL8557

Isavuconazole and warfarin

Warfarin DRUG

oral

Also known as: Coumadin

Isavuconazole and warfarin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Basilea Pharmaceutica International Ltd: collaborator

Study Sites (1)

Spaulding Clinical

West Bend, Wisconsin, 53095, United States

Location

MeSH Terms

Interventions

isavuconazole; Warfarin

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Medical Director

  Astellas Pharma Global Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2012
• First Posted: August 6, 2012
• Study Start: June 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: August 28, 2012

Record last verified: 2012-08

Locations

US (1)