study to assess the effect of food and acid reducing agents on the absorption of capivasertib in healthy participants

Conditions: Solid and Hematological Malignancies

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

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.

Keywords: crossover acid reducing agent food effect pharmacokinetics serine/threonine specific protein kinase inhibitor