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| Name | Class |
|---|---|
| Basilea Pharmaceutica International Ltd | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Isavuconazole | Drug | oral |
|
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Astellas Pharma Global Development | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Spaulding Clinical | West Bend | Wisconsin | 53095 | United States |
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| ID | Term |
|---|---|
| C508735 | isavuconazole |
| D014859 | Warfarin |
| ID | Term |
|---|---|
| D015110 | 4-Hydroxycoumarins |
| D003374 | Coumarins |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 |
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| Warfarin | Drug | oral |
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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 |
| 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 | 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 |
| 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 |
| 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 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |