Study to assess the effect of food and acid reducing agents on the absorption of Capivasertib in healthy participants

Study identifier:D3614C00005

ClinicalTrials.gov identifier:NCT04944771

EudraCT identifier:2021-000836-74

CTIS identifier:N/A

Study Complete

Official Title

An Open-label, Randomized, Crossover Study in Healthy Subjects to Evaluate the Effect of Food and Acid Reducing Agent(s) on the Pharmacokinetics of Capivasertib

Medical condition

Solid and hematological malignancies

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Capivasertib, Rabeprazole

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 58 Years

Date

Study Start Date: 26 Jul 2021

Primary Completion Date: 04 May 2022

Study Completion Date: 04 May 2022

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Crossover Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2022 by AstraZeneca

Collaborators

PAREXEL

Inclusion and exclusion 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.

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.

No locations available

Arms	Assigned Interventions
Experimental: Treatment ABC Participants will be randomized to receive oral doses of Treatment A, Treatment B and Treatment C.	Drug: Capivasertib Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F. Drug: Rabeprazole 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.
Experimental: Treatment ACB Participants will be randomized to receive oral doses of Treatment A, Treatment C and Treatment B.	Drug: Capivasertib Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F. Drug: Rabeprazole 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.
Experimental: Treatment BAC Participants will be randomized to receive oral doses of Treatment B, Treatment A and Treatment C.	Drug: Capivasertib Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F. Drug: Rabeprazole 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.
Experimental: Treatment BCA Participants will be randomized to receive oral doses of Treatment B, Treatment C and Treatment A.	Drug: Capivasertib Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F. Drug: Rabeprazole 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.
Experimental: Treatment CAB Participants will be randomized to receive oral doses of Treatment C, Treatment A and Treatment B.	Drug: Capivasertib Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F. Drug: Rabeprazole 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.
Experimental: Treatment CBA Participants will be randomized to receive oral doses of Treatment C, Treatment B and Treatment A.	Drug: Capivasertib Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F. Drug: Rabeprazole 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.
Experimental: Treatment DEF Participants will be randomized to receive oral doses of Treatment D, Treatment E and Treatment F.	Drug: Capivasertib Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F.
Experimental: Treatment DFE Participants will be randomized to receive oral doses of Treatment D, Treatment F and Treatment E.	Drug: Capivasertib Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F.
Experimental: Treatment EDF Participants will be randomized to receive oral doses of Treatment E, Treatment D and Treatment F.	Drug: Capivasertib Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F.
Experimental: Treatment EFD Participants will be randomized to receive oral doses of Treatment E, Treatment F and Treatment D.	Drug: Capivasertib Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F.
Experimental: Treatment FDE Participants will be randomized to receive oral doses of Treatment F, Treatment D and Treatment E.	Drug: Capivasertib Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F.
Experimental: Treatment FED Participants will be randomized to receive oral doses of Treatment F, Treatment E and Treatment D.	Drug: Capivasertib Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F.

Documents available

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Trial Results Summaries
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Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]