Clinical trial NCT01657825: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics of Isavuconazole
Pharmacokinetics of S- and R-warfarin
Pharmacodynamics of Warfarin
Healthy Volunteers
Keywords: isavuconazole
warfarin
Healthy Volunteers
BAL8557
Coumadin
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Basilea Pharmaceutica International Ltd
First posted: 2012-08-06
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

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.

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

Primary outcomes:
measure: Composite of Pharmacokinetic (PK) variables for S-warfarin (in plasma): AUCinf, AUClast, Cmax
timeFrame: 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:
measure: Composite of PK variables for R-warfarin (in plasma): AUCinf, AUClast, Cmax
timeFrame: 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
measure: Composite of Pharmacokinetic (PK) variables for S-warfarin and R-warfarin (in plasma): tmax, Vz /F, CL/F, and t1/2
timeFrame: 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
measure: PK variable for isavuconazole (in plasma): trough concentration (Ctrough)
timeFrame: Days 18-20 and Days 22-27, predose and Day 28 predose and 24 hours post dose
measure: Composite of PK variable for isavuconazole (in plasma): AUCtau , Cmax, and tmax
timeFrame: 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
measure: Pharmacodynamic Variables: MAXINR, AUCINR, MAXPT, and AUCPT
timeFrame: Day 1 and Day 20 predose and at 6, 12, 24, 48, 72, 96, 168, and 216 hours post-warfarin-dose
measure: Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) physical examinations, and vital signs
timeFrame: Day 1 through Day 29, Day 35 ± 2
Other outcomes:
Locations:
city: West Bend
country: United States
facility: Spaulding Clinical
state: Wisconsin
Study officials:
affiliation: Astellas Pharma Global Development
name: Medical Director
role: STUDY_DIRECTOR
References: