Study to Assess the Effect of Food and Acid Reducing Agents on the Absorption of Capivasertib in Healthy Participants

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.

Eligibility Criteria:
Inclusion Criteria:

* Provision of signed and dated, written informed consent prior to any study specific procedures.
* Healthy male and female subjects aged 18 to 58 years with suitable veins for cannulation or repeated venipuncture.
* Females must not be lactating and must be of non-childbearing potential, confirmed at screening:

  1. Postmenopausal defined as aged \> 40 years and amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone levels in the postmenopausal range.
  2. Documentation of irreversible/permanent surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation, at least 6 months prior to screening.
* Male subjects must be vasectomized, at least 6 months prior to screening, with documented post-procedural medical assessment of surgical success.
* Have a body mass index between 18.0 and 29.9 kg/m\^2 (inclusive) for males and 18 to 32 kg/m\^2 (inclusive) for females; and weigh at least 50 kg and no more than 100 kg inclusive.
* Non-smoker, defined as a subject who has not smoked previously or who has discontinued smoking.

Exclusion Criteria:

* History of any clinically significant disease or disorder.
* History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
* Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
* Any clinically significant abnormal findings in vital signs at screening and/or admission to the study center.
* Clinically significant abnormalities in glucose metabolism defined by any of the following:

  1. Diagnosis of diabetes mellitus type I or II (irrespective of management).
  2. Blood glucose value ≥ 5.9 mmol/L after fasting for at least 8 hours, at screening or on admission to study center.
  3. Glycosylated hemoglobin \> upper limit of normal (up to 6.2% \[44 mmol/mol\]).
* Any positive result on screening for serum hepatitis B surface antigen or antibody to hepatitis B core antigen, hepatitis C antibody, and human immunodeficiency virus antibody.
* Known or suspected history of drug abuse.
* Has received another new chemical entity within 3 months of the first administration of IMP in this study.
* Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
* History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to capivasertib, rabeprazole, or famotidine.
* Subjects who have previously received capivasertib.
* Subject has a positive test result for Severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction on admission.
* Subject has clinical signs and symptoms consistent with Coronavirus Disease 2019 (COVID-19) (eg, fever, dry cough, dyspnea, sore throat, anosmia/hyposmia, loss or reduced taste, and fatigue) or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission.
* History of severe COVID-19 (hospitalization, extracorporeal membrane oxygenation, mechanically ventilated).
* Subjects who are regularly exposed to the risk of COVID-19 infection as part of their daily life (eg, health care professionals working in COVID-19 wards or at emergency departments).
* Subjects who have had a COVID-19 vaccine within 3 weeks prior to screening or are planning to get a COVID-19 vaccine during the study.