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| Name | Class |
|---|---|
| Basilea Pharmaceutica International Ltd | INDUSTRY |
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The purpose of this two part study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of multiple doses of lopinavir/ritonavir and the effect of multiple doses of lopinavir/ritonavir on the pharmacokinetics of isavuconazole.
Part 1 of the study includes 12 subjects randomized to receive either isavuconazole alone or isavuconazole in combination with lopinavir/ritonavir. The purpose of Part 1 is to evaluate safety and tolerability and to establish the effect of multiple doses of lopinavir/ritonavir on isavuconazole.
Part 2, if initiated, includes 54 subjects randomized to receive isavuconazole alone, lopinavir/ritonavir alone, or isavuconazole in combination with lopinavir/ritonavir.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: isavuconazole only | Experimental | Isavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13 |
|
| Arm 2 : LPV/RTV only | Experimental | Lopinavir/ritonavir (LPV/RTV) twice daily (BID) on Days 1-12 and once on Day 13 |
|
| Arm 3: isavuconazole and LPV/RTV | Experimental | Isavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13 in combination with lopinavir/ritonavir twice daily (BID) on Days 1-13 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Isavuconazole | Drug | oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic (PK) for isavuconazole: AUCtau | (Arms 1 and 3) Area under the concentration time curve during the during time interval between consecutive dosing (AUCtau) (tau=24) | Part 1, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8,10,12,16, and 24 hours post-dose |
| Pharmacokinetic (PK) profile for isavuconazole: AUC tau and Cmax | (Arms 2 and 3) Maximum concentration (Cmax) | Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose |
| Pharmacokinetic (PK) profile for lopinavir/ritonavir: AUC tau and Cmax | (Arms 2 and 3) AUC during time interval between consecutive dosing (AUCtau) (tau=12) | Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours post dose |
| Measure | Description | Time Frame |
|---|---|---|
| PK for isavuconazole (in plasma): trough concentration (Ctrough) | (Arms 1 and 3) | Parts 1 and 2, Days 3, 5, 7, 9 and 11: pre-dose |
| PK profile for isavuconazole (in plasma): Cmax, tmax | (Arms 1 and 3) Time to attain Cmax (tmax) |
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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 |
|---|---|---|---|---|---|---|
| Parexel International | Glendale | California | 91206 | United States |
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| ID | Term |
|---|---|
| C508735 | isavuconazole |
| D061466 | Lopinavir |
| C558899 | lopinavir-ritonavir drug combination |
| ID | Term |
|---|---|
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Lopinavir/ritonavir | Drug | oral |
|
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| Parts 1 and 2, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12,16, and 24 hours post-dose |
| PK for lopinavir/ritonavir (in plasma): trough concentration (Ctrough) | (Arms 2 and 3) | Part 2, Days 3, 5, 7, 9 and 11: pre-dose |
| PK for lopinavir/ritonavir (in plasma): tmax | (Arms 2 and 3) | Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours post dose |
| Safety and tolerability of isavuconazole alone and in combination with lopinavir (LPV) and ritonavir (RTV) assessed by recording of adverse events, physical examination, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs | Part 1, Days 1 - 20 ± 2 |