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A Phase 1 Open-label, Two-cohort, One-sequence Crossover Study to Investigate the Effect of P glycoprotein Inhibitor (Itraconazole) and Inducer (Rifampin) on the Pharmacokinetics, Safety, and Tolerability of Sitravatinib in Healthy Subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 Treatment A | Active Comparator | A single-dose administration of sitravatinib malate 50 mg on Day 1. Day 12, a single dose of sitravatinib malate 50 mg will be will be followed by a 72-hour PK sample collection period. Subjects will be discharged from the CRU on Day 4 after collection of 72-hour postdose PK sample and completion of all required study procedures. |
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| Group 1 Treatment B | Active Comparator | On Days 9 to 11, itraconazole 200 mg will be administered QD in the morning. On Day 12, a single dose of sitravatinib malate 50 mg will be coadministered with itraconazole. Itraconazole QD dosing will continue on Days 13 to 18 to maintain steady state during the PK sample collection period. |
|
| Group 2 Treatment A | Active Comparator | A single-dose administration of sitravatinib malate 100 mg on Day 1 will be followed by a 72-hour PK sample collection period. Subjects will be discharged from the CRU on Day 4 after collection of 72-hour postdose PK sample and completion of all required study procedures. |
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| Group 2 Treatment B | Active Comparator | On Days 9 to 15, rifampin 600 mg will be administered QD in the morning. On Day 16, a single dose of sitravatinib malate 100 mg will be coadministered with rifampin followed by a 72 hour PK sample collection period. Rifampin QD dosing will continue on Days 17 to 22 to maintain steady state during the PK sample collection period. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sitravatinib 50 mg | Drug | 50 mg Sitravatinib on Day 1 (Group 1A) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics - Cmax (sitravatinib) | Maximum observed plasma concentration | Up to Day 168 hours after dosing |
| Pharmacokinetics - AUC∞ (sitravatinib) | Area under the plasma concentration-time curve from time zero extrapolated to infinity | Up to 168 hours after dosing |
| Pharmacokinetics - AUClast (sitravatinib) | Area under the curve from time zero to the last measured time point | Up to 168 hours after dosing |
| Pharmacokinetics - tmax (sitravatinib) | Terminal elimination half-life | Up to 168 hours after dosing |
| Pharmacokinetics - CL/F (sitravatinib) | Apparent total plasma clearance when dosed orally | Up to 168 hours after dosing |
| Pharmacokinetics - Vz/F (sitravatinib) | Apparent volume of distribution when dosed orally | Up to 168 hours after dosing |
| Pharmacokinetics - uf (sitravatinib) | Unbound fraction | Up to 168 hours after dosing |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events (AEs) | Incidence and severity of AEs | Up to 12 weeks from screening |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Labcorp Drug Development Clinical Research Unit | Dallas | Texas | 75247 | United States |
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| ID | Term |
|---|---|
| C000611865 | sitravatinib |
| D017964 | Itraconazole |
| D000077402 | Pantoprazole |
| D012293 | Rifampin |
| D015738 | Famotidine |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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This is a Phase 1, single-center, open-label, 2-cohort, 1-sequence crossover study to investigate the effect of coadministration of a P glycoprotein (P-gp) inhibitor, itraconazole, (Cohort 1) and a P-gp inducer, rifampin, (Cohort 2) in healthy subjects.
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| Sitravatinib 100 mg | Drug | 100 mg Sitravatinib on Day 1 (Group 2A) |
|
|
| Itraconazole | Drug | Itraconazole QD from Day 9 to Day 18, and Sitravatinib 50 mg at Day 12 (Group 1B) |
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| Rifampin | Drug | Rifampin QD from Day 9 to Day 22, and Sitravatinib 100 mg at Day 16 (Group 2B) |
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| D010879 |
| Piperazines |
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D013844 | Thiazoles |