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.

An Open-Label, Five-Period Study in Healthy Subjects to Investigate the Relative Bioavailability of AZD5055 Film-Coated Tablet Versus AZD5055 Oral Suspension Formulation, the Absolute Oral Bioavailability of AZD5055 and to Evaluate the Effect of Food and an Acid Reducing Agent on the Pharmacokinetics of AZD5055.

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).

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: AZD5055 solution for infusion; Drug: AZD5055 oral suspension; Drug: AZD5055 film-coated tablet; Drug: AZD5055 film-coated tablet; Drug: Rabeprazole, Delayed-release tablet; Drug: Rabeprazole, Delayed-release tablet

Detailed Description

This will be an Open-Label, Five-Period Study in healthy subjects. The study will comprise of a Screening Period of maximum 28 days.

The treatment groups are as follows:

• Treatment A: AZD5055 solution for infusion as 20-minute infusion and an overnight fasted state after the 20-minute infusion.
• Treatment B: AZD5055 oral suspension and an overnight fasted state after the oral suspension.
• Treatment C: AZD5055 film-coated tablet and an overnight fasted state after the film-coated tablet..
• Treatment D: AZD5055 film-coated tablet, fed state (after a high-fat, high-calorie standard breakfast).
• Treatment E: Twice daily oral doses of 20 mg rabeprazole for 3 days prior a single dose of AZD5055 film-coated tablet under fasted conditions, and then rabeprazole will be continued for 2 days.
• Treatment F: Twice daily oral doses of 20 mg rabeprazole continuing from Treatment E prior to a single dose of AZD5055 film-coated tablet under fed conditions (low-fat standard breakfast) and then rabeprazole will be continued for 2 days.

Five (5) periods during which subjects will participate from Day -1 of Period 1 to 72 hours after the AZD5055 dose in Period 5.

• Period 1: On Day 1, the subjects will receive either Treatment A or Treatment B.
• Period 2: On Day 4, the subjects will receive Treatment C.
• Period 3: On Day 8, the subjects will receiveTreatment D.
• Period 4: On Day 10, three days prior to Day 1, rabeprazole will be administered twice daily. On Day 13, subject will receive Treatment E.
• Period 5: On Day 17, the subjects will receive Treatment F. Rabeprazole will continue twice daily, the last dose is on the evening of Study Day 18.

A Follow-up Visit, or telephone call, approximately 6 days after the last AZD5055 dose in Period 5.

There will be a minimum washout of 3 days between the AZD5055 dose administration in Period 1 and Period 2 and a minimum washout of 4 days between AZD5055 doses administrations for subsequent study periods.

Each subject will participate in the study for approximately 8 weeks.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Brooklyn, Maryland, United States, 21225
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. 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.
2. 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.
3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study drug.
4. 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.
5. Individuals with chronic infections or who are at increased risk of infection.
6. History of cancer within the last 10 years (20 years for breast cancer). Any history of lymphoma is not allowed.
7. History of osteoporosis, osteomalacia, Paget's disease of the bone, thyrotoxicosis, rheumatoid arthritis, Cushing's disease, or a pathological fracture.
8. History of a traumatic fracture within 6 months of the Screening Visit.
9. Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis.
10. 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.
11. Untreated tuberculosis (TB) or a positive result for the Interferon gamma release assay (IGRA) (ie, QuantiFERON TB Gold).
12. Any positive result at Screening for serum hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody, and HIV antibody.
13. 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).
14. Confirmed COVID-19 infection during at admission.
15. 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.
16. Known or suspected history of drug abuse.
17. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity.
18. Current smokers or use of any tobacco in any other form.
19. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
20. Use of drugs with enzyme-inducing properties such as St John's Wort.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; 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; 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.
Experimental: Treatment B; Subjects will receive oral suspension of AZD5055 in an overnight fasted state on Day 1 in Period 1.	Drug: AZD5055 oral suspension; Subjects will receive single dose of AZD5055 oral suspension on Day 1 of the respective period in overnight fasted state.
Experimental: Treatment C; 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; Subjects will receive single oral dose of AZD5055 film-coated tablets on Day 1 of the respective period in overnight fasted state.; Drug: AZD5055 film-coated tablet; Subjects will receive single oral dose of AZD5055 film-coated tablets on Day 1 of the respective period in fed state (either a high fat meal or low-fat meal calorie standard breakfast)
Experimental: Treatment D; 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; Subjects will receive single oral dose of AZD5055 film-coated tablets on Day 1 of the respective period in overnight fasted state.; Drug: AZD5055 film-coated tablet; Subjects will receive single oral dose of AZD5055 film-coated tablets on Day 1 of the respective period in fed state (either a high fat meal or low-fat meal calorie standard breakfast)
Experimental: Treatment E; 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; Subjects will receive single oral dose of AZD5055 film-coated tablets on Day 1 of the respective period in overnight fasted state.; Drug: AZD5055 film-coated tablet; Subjects will receive single oral dose of AZD5055 film-coated tablets on Day 1 of the respective period in fed state (either a high fat meal or low-fat meal calorie standard breakfast); Drug: Rabeprazole, Delayed-release tablet; 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].; Drug: Rabeprazole, Delayed-release tablet; Subjects will receive oral doses of rabeprazole twice daily prior to AZD5055 single dose under fed conditions (low-fat standard breakfast) and then continued for 2 days.
Experimental: Treatment F; 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; Subjects will receive single oral dose of AZD5055 film-coated tablets on Day 1 of the respective period in overnight fasted state.; Drug: AZD5055 film-coated tablet; Subjects will receive single oral dose of AZD5055 film-coated tablets on Day 1 of the respective period in fed state (either a high fat meal or low-fat meal calorie standard breakfast); Drug: Rabeprazole, Delayed-release tablet; 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].; Drug: Rabeprazole, Delayed-release tablet; Subjects will receive oral doses of rabeprazole twice daily prior to AZD5055 single dose under fed conditions (low-fat standard breakfast) and then continued for 2 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel
• Investigators: Principal Investigator: Ronald Goldwater, MD, PAREXEL Early Phase Clinical Unit Baltimore

Publications and helpful links

Helpful Links

• D8960C00002_CSR Synopsis_Redacted.pdf

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2022
• Primary Completion (Actual): February 9, 2023
• Study Completion (Actual): February 9, 2023

Study Registration Dates

• First Submitted: November 4, 2022
• First Submitted That Met QC Criteria: November 25, 2022
• First Posted (Actual): November 30, 2022

Study Record Updates

• Last Update Posted (Actual): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Healthy subjects; Bioavailability; Food Effect; Acid Reducing Agent; pH-dependent solubility
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Rabeprazole
• Other Study ID Numbers: D8960C00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing 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
• IPD Sharing 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No