Drug Interaction Study of Isavuconazole and Warfarin in Healthy Male Subjects
This study has been completed.
Sponsor:
Astellas Pharma Global Development, Inc.
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
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Pharmacokinetics of Isavuconazole Pharmacokinetics of S- and R-warfarin Pharmacodynamics of Warfarin Healthy Volunteers |
Drug: Isavuconazole Drug: Warfarin |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label |
| 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 |
Resource links provided by NLM:
Further study details as provided by Astellas Pharma Inc:
Primary Outcome Measures:
- 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)
Secondary Outcome Measures:
- 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 ]
| Enrollment: | 20 |
| Study Start Date: | June 2012 |
| Study Completion Date: | July 2012 |
| Primary Completion Date: | July 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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
|
Drug: Isavuconazole
oral
Other Name: BAL8557
Drug: Warfarin
oral
Other Name: Coumadin
|
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| Ages Eligible for Study: | 18 Years to 55 Years |
| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | Yes |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01657825
Locations
| United States, Wisconsin | |
| Spaulding Clinical | |
| West Bend, Wisconsin, United States, 53095 | |
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Basilea Pharmaceutica International Ltd
Investigators
| Study Director: | Medical Director | Astellas Pharma Global Development |
More Information
No publications provided
| Responsible Party: | Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ) |
| ClinicalTrials.gov Identifier: | NCT01657825 History of Changes |
| Other Study ID Numbers: | 9766-CL-0033 |
| Study First Received: | August 2, 2012 |
| Last Updated: | August 27, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Astellas Pharma Inc:
|
isavuconazole warfarin Healthy Volunteers BAL8557 Coumadin |
Additional relevant MeSH terms:
|
Warfarin Anticoagulants Hematologic Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on June 18, 2013