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: * A screening period of maximum 21 days; * A fixed sequence of 3 treatment periods: Treatment Period 1: Capivasertib only, Treatment Period 2: Itraconazole pre-treatment (run-in) period, and Treatment Period 3: Capivasertib and itraconazole in combination. * A Follow-up Visit at 7 to 14 days after the last capivasertib PK sample in Treatment Period 3. 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
11
Subects will be administered single doses of capiversatib on Day 1 and Day 6.
Subjects will be administered itraconazole twice daily on Day 3, followed by once daily doses in the morning for 4 days.
Research Site
Berlin, Germany
Area under plasma concentration-time curve from zero to infinity (AUCinf) of capivasertib
Assessment of AUCinf of capivasertib.
Time frame: 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.
Time frame: 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
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).
Time frame: 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 delay between drug administration and the first observed concentration in plasma (tlag) of capivasertib
Assessment of tlag of capivasertib.
Time frame: 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).
Time frame: 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)
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Assessment of t½λz of capivasertib and its major metabolite (AZ14102143).
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From Screening until Follow-upVisit / Early Termination (7-14 days after last PK sample)