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| Name | Class |
|---|---|
| Basilea Pharmaceutica International Ltd | INDUSTRY |
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The purpose of the study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics (PK) of sirolimus after single dose administration.
Subjects will receive a single dose of sirolimus on Day 1 followed by a 21 day wash-out period (time from sirolimus dosing to isavuconazole dosing). On Days 22 and 23, isavuconazole will be dosed three times daily (TID). On Days 24 through 34, isavuconazole will be administered once daily (QD). All subjects will be administered a single dose of sirolimus on Day 26.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| isavuconazole and sirolimus | Experimental | Single dose of sirolimus on Days 1 and 26, isavuconazole 3 times a day (TID) for 2 days (Days 22 to 23) followed by once a day (QD) for 11 days |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| isavuconazole | Drug | Oral |
|
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| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (PK) of sirolimus in whole blood: AUCinf | Area under the concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) | Days 1 and 26 at predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours postdose |
| PK of sirolimus in whole blood: AUClast | AUC from the time of dosing to the last quantifiable concentration (AUClast) | Days 1 and 26 at predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours postdose |
| PK of sirolimus in whole blood: Cmax | Maximum concentration (Cmax) | Days 1 and 26 at predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| Composite of PK variables of sirolimus in whole blood: tmax, Vz/F, CL/F, and t 1/2 | 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 26 at predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours postdose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Senior Medical Director | Astellas Pharma Global Development, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Covance | Dallas | Texas | 75247 | United States |
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| sirolimus | Drug | Oral |
|
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| PK variable of isavuconazole in plasma: Ctrough | trough concentration (Ctrough) | Day 24 and Days 28 through 35 predose |
| Composite of PK variables of isavuconazole in plasma: AUCtau, Cmax, and tmax | AUC during the time interval between consecutive dosing (AUCtau) | Day 25, predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours postdose; Day 26 predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours postdose |
| ID | Term |
|---|---|
| C508735 | isavuconazole |
| D020123 | Sirolimus |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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