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| Name | Class |
|---|---|
| Parexel | INDUSTRY |
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This study will be an open-label, fixed sequence study in healthy subjects (vasectomized males and females of non-childbearing potential), performed at a single study centre.
The study will comprise:
There will be no washout between Treatment Period 2 and Treatment Period 3. Each subject will be involved in the study for up to 7 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Capivasertib + Itraconazole | Experimental | Subjects will receive a single oral dose of capivasertib on Day 1 during treatment period 1, itraconazole on Days 3, 4, and 5 during treatment period 2, and single oral dose of capivasertib plus a dose of itraconazole on Day 6, followed by itraconazole alone on Day 7 during treatment period 3. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Capivasertib | Drug | Subects will be administered single doses of capiversatib on Day 1 and Day 6. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area under plasma concentration-time curve from zero to infinity (AUCinf) of capivasertib | Assessment of AUCinf of capivasertib. | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6 |
| Maximum observed plasma (peak) drug concentration (Cmax) of capivasertib | Assessment of Cmax of capivasertib. | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast) of capivasertib and its major metabolite (AZ14102143) | Assessment of AUClast of capivasertib and its major metabolite (AZ14102143). | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rainard Fuhr, Dr. | Parexel | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Berlin | 14050 | Germany |
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| Itraconazole | Drug | Subjects will be administered itraconazole twice daily on Day 3, followed by once daily doses in the morning for 4 days. |
|
| Time delay between drug administration and the first observed concentration in plasma (tlag) of capivasertib | Assessment of tlag of capivasertib. | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6 |
| Time to reach peak or maximum observed concentration or response following drug administration (tmax) of capivasertib and its major metabolite (AZ14102143) | Assessment of tmax of capivasertib and its major metabolite (AZ14102143). | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6 |
| Half-life associated with terminal slope (λz) of a semi-logarithmic concentration time curve (t½λz) of capivasertib and its major metabolite (AZ14102143) | Assessment of t½λz of capivasertib and its major metabolite (AZ14102143). | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6 |
| Terminal elimination rate constant (λz) of capivasertib and its major metabolite (AZ14102143) | Assessment of λz of capivasertib and its major metabolite (AZ14102143). | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6 |
| Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of capivasertib | Assessment of CL/F of capivasertib. | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6 |
| Volume of distribution (apparent) at steady state following extravascular administration (Vz/F) (based on terminal phase) of capivasertib | Assessment of Vz/F of capivasertib. | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6 |
| AUCinf of major metabolite (AZ14102143) of capivasertib | Assessment of AUCinf of major metabolite (AZ14102143) of capivasertib. | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6 |
| Cmax of major metabolite (AZ14102143) of capivasertib | Assessment of Cmax of major metabolite (AZ14102143) of capivasertib. | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6 |
| Number of subjects with serious and non-serious adverse events | Assessment of safety and tolerability of capivasertib alone and in combination with itraconazole. | From Screening until Follow-upVisit / Early Termination (7-14 days after last PK sample) |
| ID | Term |
|---|---|
| C575618 | capivasertib |
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010879 | Piperazines |
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