Study to Assess the Effect of Food and Acid Reducing Agents on the Absorption of Capivasertib in Healthy Participants
Condition: Solid and Hematological Malignancies
MeSH terms: Hematologic Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      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
    

Detailed description: 
      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.
    

Intervention name(s): Capivasertib; Rabeprazole
Intervention type(s): Drug; Drug
Intervention description(s): 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.
Intervention MeSH terms: Rabeprazole
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Crossover; Acid reducing agent; Food effect; Pharmacokinetics; Serine/threonine specific protein kinase inhibitor