This is a two-part, open-label, randomized, crossover study in healthy subjects (vasectomized males and women of non-childbearing potential), performed at 2 study centers
Part 1 of the study will comprise: * A screening period of maximum 28 days. * Three treatment periods \[Treatment A: Single oral dose of capivasertib in overnight fasted state, Treatment B:Single oral dose of capivasertib in fed state (high-fat, high-calorie breakfast) and Treatment C:Twice daily oral doses of rabeprazole for 3 days and a single dose on Day 1, and a single oral dose of capivasertib in fasted conditions\] during which subjects will be resident from the morning of Day -1 (Day -4 for subjects receiving rabeprazole \[Treatment C\]) and discharged after the last pharmacokinetic (PK) sample collection, 48 hours after dosing of capivasertib of each treatment period. * A final visit 7 to 14 days after the last capivasertib PK sample in Treatment Period 3. Part 2 of the study will only be initiated if the findings from Part 1 show an interaction or are inconclusive. Part 2 of the study will comprise: * A screening period of at least 28 days. * Three treatment periods \[Any 3 treatments: Treatment D:Single oral dose of capivasertib in overnight fasted state, Treatment E: Single oral dose of capivasertib in fed state (low-fat, low-calorie breakfast), Treatment F: Single oral dose of capivasertib in partially fasted conditions (food restricted from 2 hours prior to dosing until 1 hour after dosing), Treatment G: Single oral dose of capivasertib and single dose of famotidine in fasted condition and Treatment H: Twice daily oral doses of rabeprazole for 3 days (Days -3 to -1) and a single oral dose of capivasertib in fed state\] during which subjects will be resident from the morning of Day -1 (Day -4 for subjects receiving rabeprazole \[Treatment H\]) and will be discharged after the last PK sample collection 48 hours after dosing of capivasertib of each treatment period. * A final visit 7 to 14 days after the last capivasertib PK sample in Treatment Period 3. The interim results from Part 1 indicated a potentially clinically relevant food interaction only and therefore Treatments D, E, and F will be studied in Part 2.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F.
Participants will receive twice daily oral doses of rabeprazole for 3 days (Days -3 to -1) and a single dose on the morning of Day 1 for Treatment C.
Research Site
Berlin, Germany
Cmax of Capivasertib
Maximum observed plasma (peak) drug concentration (Cmax) of capivasertib when administered alone under fed and fasted conditions, and in combination with acid reducing agent(s) rabeprazole and famotidine (if required).
Time frame: Part 1 and Part 2: From Day 1 to Day 3
AUCinf of Capivasertib
Area under plasma concentration time curve from zero to infinity (AUCinf) of capivasertib when administered alone under fed and fasted conditions, and in combination with acid reducing agent(s) rabeprazole and famotidine (if required).
Time frame: Part 1 and Part 2: From Day 1 to Day 3
AUClast of Capivasertib
Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of capivasertib when administered alone under fed and fasted conditions, and in combination with acid reducing agent(s) rabeprazole and famotidine (if required).
Time frame: Part 1 and Part 2: From Day 1 to Day 3
Number of participants with serious and non-serious adverse events
Safety and tolerability of capivasertib when administered alone under fed and fasted conditions, and in combination with acid reducing agent(s) rabeprazole and famotidine (if required).
Time frame: Part 1: From Screening (Day -28 to Day -5) upto Follow-up Visit/Early Termination (7 to 14 days); Part 2: From Screening (Day -28 to Day -2) upto Follow-up Visit/Early Termination (7 to 14 days)
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