A Study to Compare Bioavailability of AZD5055 Film-coated Tablet With AZD5055 Oral Suspension and to Assess the Effect of Food and an Acid Reducing Agent on Pharmacokinetics (PK) of AZD5055 in Healthy Subjects.

NCT05630677 | Completed Phase 1 FDA Drug

• 1 other identifier: D8960C00002
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This study will estimate the relative bioavailability of AZD5055 film-coated tablet as compared to AZD5055 oral suspension. The study will also assess the absolute bioavailabilty of AZD5055 and the effect of food and an acid reducing agent, rabeprazole, on the PK of AZD5055 film-coated tablets when given with food (fed state) or without food (fasted state).

Conditions

Healthy Volunteers

Keywords

Acid Reducing Agent; Bioavailability; Healthy subjects; pH-dependent solubility; Food Effect

Outcome Measures

Primary Outcomes (3)

• Area under concentration time curve from time 0 to infinity (AUCinf)

  * To estimate the relative bioavailability of AZD5055 film-coated tablet formulation versus AZD5055 oral suspension formulation. * To estimate the absolute bioavailability of AZD5055 oral suspension and AZD5055 film-coated tablet formulation. * To assess the effect of the acid reducing agent, rabeprazole, on the PK of AZD5055 alone and in combination with acid reducing agent. * To assess the effect of the acid reducing agent, rabeprazole, on the PK of AZD5055, when AZD5055 is administered.

  Day 1-6, 8-10, 13-15, 17-19

• Area under the concentration time curve from time 0 to the last quantifiable concentration (AUClast)

  * To estimate the relative bioavailability of AZD5055 film-coated tablet formulation versus AZD5055 oral suspension formulation. * To estimate the absolute bioavailability of AZD5055 oral suspension and AZD5055 film-coated tablet formulation. * To assess the effect of food on the pharmacokinetic (PK) parameters of AZD5055 in the fed and fasted state. * To assess the effect of the acid reducing agent, rabeprazole, on the PK of AZD5055 alone and in combination with acid reducing agent. * To assess the effect of the acid reducing agent, rabeprazole, on the PK of AZD5055, when AZD5055 is administered in fasted and fed state.

  Day 1-6, 8-10, 13-15, 17-19

• Maximum observed concentration (Cmax)

  * To estimate the relative bioavailability of AZD5055 film-coated tablet formulation versus AZD5055 oral suspension formulation. * To estimate the absolute bioavailability of AZD5055 oral suspension and AZD5055 film-coated tablet formulation. * To assess the effect of food on the pharmacokinetic (PK) parameters of AZD5055 in the fed and fasted state. * To assess the effect of the acid reducing agent, rabeprazole, on the PK of AZD5055 alone and in combination with acid reducing agent. * To assess the effect of the acid reducing agent, rabeprazole, on the PK of AZD5055, when AZD5055 is administered in fasted and fed state.

  Day 1-6, 8-10, 13-15, 17-19

Study Arms (6)

Treatment A

EXPERIMENTAL

Subjects will receive AZD5055 solution as a 20-minute infusion in overnight fasted state on Day 1 in Period 1.

Drug: AZD5055 solution for infusion

Treatment B

EXPERIMENTAL

Subjects will receive oral suspension of AZD5055 in an overnight fasted state on Day 1 in Period 1.

Drug: AZD5055 oral suspension

Treatment C

EXPERIMENTAL

Subjects will receive AZD5055 film-coated tablet in overnight fasted state on Day 1 (Study Day 4) in Period 2.

Drug: AZD5055 film-coated tablet

Treatment D

EXPERIMENTAL

Subjects will receive a standardized high-fat breakfast 30 minutes before film-coated tablet of AZD5055 administered as On Day 1 (Study Day 8) in Period 3.

Drug: AZD5055 film-coated tablet

Treatment E

EXPERIMENTAL

Subjects will receive rabeprazole twice daily on Day 10. On Day 1 (Study Day 13), AZD5055 film-coated tablet will be administered, under fasted conditions, together with rabeprazole and rabeprazole dosing will continue twice daily in Period 4.

Drug: AZD5055 film-coated tablet; Drug: Rabeprazole, Delayed-release tablet

Treatment F

EXPERIMENTAL

Subjects will receive a low-fat breakfast 30 minutes before AZD5055 film-coated tablet administered together with rabeprazole on Day 17. Rabeprazole will continue twice daily, the last dose is on the evening of Study Day 18 in Period 5.

Drug: AZD5055 film-coated tablet; Drug: Rabeprazole, Delayed-release tablet

Interventions

AZD5055 solution for infusion DRUG

Subjects will receive a single dose intravenous infusion of AZD5055 as 20-minute infusion on Day 1 of the respective period in overnight fasted state.

Treatment A

AZD5055 oral suspension DRUG

Subjects will receive single dose of AZD5055 oral suspension on Day 1 of the respective period in overnight fasted state.

Treatment B

AZD5055 film-coated tablet DRUG

Subjects will receive single oral dose of AZD5055 film-coated tablets on Day 1 of the respective period in overnight fasted state.

Treatment C; Treatment E

Rabeprazole, Delayed-release tablet DRUG

Subjects will receive oral doses of rabeprazole twice daily 3 days prior to AZD5055 single dose and 4 days after the AZD5055 single dose including the day that AZD5055 is dosed under fasted conditions \[Study Day 10 to 18\].

Treatment E

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female (of non-childbearing potential) subjects aged 18 to 55 years.
• Female subjects must have a negative pregnancy test.
• Male subjects must adhere to the contraception methods as per Protocol.
• Have a BMI between 18 and 30 kg/m2 inclusive.

You may not qualify if:

• History of any clinically significant disease or disorder which may either put the subject at risk because of participation in the study or influence the results or the subject's ability to participate in the study.
• Ongoing acute Gastrointestinal (GI), hepatic, or renal disease, a history of chronic GI, hepatic, or renal disease, pancreatic disease, diabetes mellitus, or any 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 study drug.
• Ongoing acquired or inherited immunodeficiency disorders, including but not limited to Human Immunodeficiency Virus (HIV) or common variable immunodeficiency, or the subject is taking immune replacement therapy.
• Individuals with chronic infections or who are at increased risk of infection.
• History of cancer within the last 10 years (20 years for breast cancer). Any history of lymphoma is not allowed.
• History of osteoporosis, osteomalacia, Paget's disease of the bone, thyrotoxicosis, rheumatoid arthritis, Cushing's disease, or a pathological fracture.
• History of a traumatic fracture within 6 months of the Screening Visit.
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis.
• Abnormal vital signs. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG.
• Untreated tuberculosis (TB) or a positive result for the Interferon gamma release assay (IGRA) (ie, QuantiFERON TB Gold).
• Any positive result at Screening for serum hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody, and HIV antibody.
• History of severe COVID-19 infection requiring hospitalization within the last 12 months prior to Screening, or clinical history compatible with Long COVID-19 (symptoms beyond 12 weeks of acute infection).
• Confirmed COVID-19 infection during at admission.
• Has received live or live attenuated vaccine in the 30 days prior to dosing, the first dose of COVID- vaccine within 30 days prior to randomization, or a COVID-19 vaccine second or booster vaccination within 10 days of Screening.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Brooklyn, Maryland, 21225, United States

Location

Related Links

• D8960C00002\_CSR Synopsis\_Redacted.pdf

MeSH Terms

Interventions

Rabeprazole; Tablets, Enteric-Coated

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; Delayed-Action Preparations; Dosage Forms; Pharmaceutical Preparations; Tablets

Study Officials

• Ronald Goldwater, MD

  PAREXEL Early Phase Clinical Unit Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 4, 2022
• First Posted: November 30, 2022
• Study Start: November 4, 2022
• Primary Completion: February 9, 2023
• Study Completion: February 9, 2023
• Last Updated: March 4, 2024

Record last verified: 2024-03

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 deidentified 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

US (1)