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This is an open label, fixed sequence, 1-way crossover drug-drug interaction (DDI) study in healthy participants.
This is a phase 1, open-label, fixed sequence, 1-way crossover study examining the effect of itraconazole on the pharmacokinetics, safety and tolerability after varegacestat single dose administration to healthy participants. This is a 2-period study. In period 1 a single dose of varegacestat will be administered with PK evaluated predose and up to 192 hours postdose. There will be a 14 -day washout between period 1 and period 2. In period 2, itraconzole will be administered once daily for 18 consecutive days. Beginning on Day 4 of Period 2 a single dose of varegacestat will be administered 30 minutes after itraconazole dosing. Blood samples for PK will be collected prior to varegacestat dosing and up to 744 hours post varegacestat dosing for varegacestat and its metabolite.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Arm | Experimental | Period 1: varegacestat administration for PK followed by Period 2: itraconazole and varegacestat administration for PK and DDI |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| varegacestat | Drug | Experimental intervention |
| |
| Itraconazole (200 mg) |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of itraconazole on the PK of varegacestat in healthy participants. | AUC0-t for varegacestat administered with and without itraconazole. | Up to 5 weeks |
| Effect of itraconazole on the PK of varegacestat in healthy participants. | AUC0-inf for varegacestat administered with and without itraconazole. | Up to 5 weeks |
| Effect of itraconazole on the PK of varegacestat in healthy participants. | Cmax for varegacestat administered with and without itraconazole. | Up to 5 weeks |
| Effect of itraconazole on the PK of varegacestat in healthy participants. | Tmax for varegacestat administered with and without itraconazole. | Up to 5 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of varegacestat in the presence of itraconazole in healthy participants. | Number of subjects who experience treatment-emergent adverse events (TEAEs) | Up to 2 months |
| Safety and tolerability of varegacestat in the presence of itraconazole in healthy participants. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michelle Valentine | Celerion | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Celerion | Tempe | Arizona | 85289 | United States |
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| ID | Term |
|---|---|
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Drug |
Intervention to evaluate DDI with experimental intervention |
|
Number of subjects who experience abnormalities in clinical laboratory tests such as serum chemistry and hematology |
| Up to 2 months |
| Safety and tolerability of varegacestat in the presence of itraconazole in healthy participants. | Number of subjects who experience 12-lead ECG abnormalities | Up to 2 months |
| Ctrough of itraconazole and hydroxy-itraconazole in combination with varegacestat in healthy participants. | Ctrough. values on prior to dosing itraconazole | Up to 5 weeks |
| D010879 |
| Piperazines |