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

NCT04944771 | Completed Phase 1 FDA Drug

• 2 other identifiers: D3614C000052021-000836-74
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Solid and Hematological Malignancies

Keywords

Crossover; Acid reducing agent; Food effect; Pharmacokinetics; Serine/threonine specific protein kinase inhibitor

Outcome Measures

Primary Outcomes (3)

• 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).

  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).

  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).

  Part 1 and Part 2: From Day 1 to Day 3

Secondary Outcomes (1)

• Number of participants with serious and non-serious adverse events

  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)

Study Arms (12)

Treatment ABC

EXPERIMENTAL

Participants will be randomized to receive oral doses of Treatment A, Treatment B and Treatment C.

Drug: Capivasertib; Drug: Rabeprazole

Treatment ACB

EXPERIMENTAL

Participants will be randomized to receive oral doses of Treatment A, Treatment C and Treatment B.

Drug: Capivasertib; Drug: Rabeprazole

Treatment BAC

EXPERIMENTAL

Participants will be randomized to receive oral doses of Treatment B, Treatment A and Treatment C.

Drug: Capivasertib; Drug: Rabeprazole

Treatment BCA

EXPERIMENTAL

Participants will be randomized to receive oral doses of Treatment B, Treatment C and Treatment A.

Drug: Capivasertib; Drug: Rabeprazole

Treatment CAB

EXPERIMENTAL

Participants will be randomized to receive oral doses of Treatment C, Treatment A and Treatment B.

Drug: Capivasertib; Drug: Rabeprazole

Treatment CBA

EXPERIMENTAL

Participants will be randomized to receive oral doses of Treatment C, Treatment B and Treatment A.

Drug: Capivasertib; Drug: Rabeprazole

Treatment DEF

EXPERIMENTAL

Participants will be randomized to receive oral doses of Treatment D, Treatment E and Treatment F.

Drug: Capivasertib

Treatment DFE

EXPERIMENTAL

Participants will be randomized to receive oral doses of Treatment D, Treatment F and Treatment E.

Drug: Capivasertib

Treatment EDF

EXPERIMENTAL

Participants will be randomized to receive oral doses of Treatment E, Treatment D and Treatment F.

Drug: Capivasertib

Treatment EFD

EXPERIMENTAL

Participants will be randomized to receive oral doses of Treatment E, Treatment F and Treatment D.

Drug: Capivasertib

Treatment FDE

EXPERIMENTAL

Participants will be randomized to receive oral doses of Treatment F, Treatment D and Treatment E.

Drug: Capivasertib

Treatment FED

EXPERIMENTAL

Participants will be randomized to receive oral doses of Treatment F, Treatment E and Treatment D.

Drug: Capivasertib

Interventions

Capivasertib DRUG

Participants will receive single oral dose of capivasertib on Day 1 for Treatments A, B, C, D, E and F.

Treatment ABC; Treatment ACB; Treatment BAC; Treatment BCA; Treatment CAB; Treatment CBA; Treatment DEF; Treatment DFE; Treatment EDF; Treatment EFD; Treatment FDE; Treatment FED

Rabeprazole DRUG

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.

Treatment ABC; Treatment ACB; Treatment BAC; Treatment BCA; Treatment CAB; Treatment CBA

Eligibility Criteria

• Age: 18 Years - 58 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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.
• 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.

You may not qualify if:

• 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:
• Diagnosis of diabetes mellitus type I or II (irrespective of management).
• Blood glucose value ≥ 5.9 mmol/L after fasting for at least 8 hours, at screening or on admission to study center.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

capivasertib; Rabeprazole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2021
• First Posted: June 30, 2021
• Study Start: July 26, 2021
• Primary Completion: May 4, 2022
• Study Completion: May 4, 2022
• Last Updated: May 9, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

DE (1)