A Study to Investigate the Pharmacokinetics of AZD2389 When Administered Alone and in Combination With Itraconazole in Healthy Participants

An Open-label, Fixed Sequence Study in Healthy Participants to Assess the Pharmacokinetics of AZD2389 When Administered Alone and in Combination With Itraconazole

The purpose of this study is to assess the pharmacokinetics (PK) of AZD2389 when administered alone and in combination with itraconazole in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: AZD2389; Drug: Itraconazole

Detailed Description

This study will be an open-label, fixed sequence, Drug-Drug Interaction (DDI) study consisting of 3 periods.

The study will comprise:

• A screening period of maximum 28 days
• Period 1
• Period 2
• Period 3
• A Follow-up Visit 7 to 14 days after the last PK sample has been collected.

• Study Type: Interventional
• Enrollment (Actual): 16
• 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: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
• Females of non-childbearing potential must be postmenopausal for at least 12 months or have documentation of irreversible surgical sterilization.
• Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods.
• Have a Body Mass Index (BMI) between 18 and 32 kg/m2 inclusive and weigh at least 50 kg.

Exclusion Criteria:

• History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
• 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 important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
• Abnormal laboratory values, clinically important abnormalities or abnormal vital signs
• Any positive result on screening for serum Hepatitis B surface antigen/antibody, Hepatitis C, or Human Immunodeficiency Virus.
• Current smokers (within 3 months prior to screening visit) or history of alcohol and drug abuse
• History of severe allergy or hypersensitivity
• Excessive intake of caffeine-containing drinks or food
• Use of drugs with enzyme inducing properties or use of any prescribed or nonprescribed medication including antacids, analgesics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD2389 and Itraconazole; AZD2389 is dosed on days 1 and 6. Itraconazole is dosed on days 3,4,5,6,7, with the dose on day 6 coming after AZD2389.	Drug: AZD2389; AZD2389 is administered orally; Drug: Itraconazole; Itraconazole is administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed drug concentration (Cmax) of AZD2389	To assess the effect of itraconazole on the Cmax of AZD2389.	Day 1 to Day 8
Area under concentration-timecurve from time zero to infinity (AUCinf) of AZD2389	To assess the effect of itraconazole on the AUCinf of AZD2389.	Day 1 to Day 8
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of AZD2389	To assess the effect of itraconazole on the AUClast of AZD2389.	Day 1 to Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apparent total body clearance (CL/F) of AZD2389	To describe the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with itraconazole	Day 1 to Day 8
Apparent volume of distribution based on the terminal phase (Vz/F) of AZD2389	To describe the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with itraconazole	Day 1 to Day 8
Terminal elimination half-life (t1/2λz) of AZD2389	To describe the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with itraconazole.	Day 1 to Day 8
Time to reach maximum observed concentration (tmax) of AZD2389	To describe the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with itraconazole.	Day 1 to Day 8
Ratio of Test treatment (AZD2389 + itraconazole) to Reference (AZD2389) based on Cmax (RCmax) of AZD2389	To describe the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with itraconazole.	Day 1 to Day 8
Ratio of Test treatment (AZD2389 + itraconazole) to Reference (AZD2389) based on AUClast (RAUClast) of AZD2389	To describe the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with itraconazole.	Day 1 to Day 8
Ratio of Test treatment (AZD2389 + itraconazole) to Reference (AZD2389) based on AUCinf (RAUCinf) of AZD2389	To describe the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with itraconazole.	Day 1 to Day 8
Renal Clearance (CLR) of AZD2389	To describe the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with itraconazole.	Day 1 to Day 8
Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 (Ae(t1-t2)) of AZD2389	To describe the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with itraconazole.	Day 1 to Day 8
Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 (fe(t1-t2)) of AZD2389	To describe the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with itraconazole.	Day 1 to Day 8
Percent change from baseline in fibroblast activation protein (FAP) inhibition	To evaluate the pharmacodynamics (PD) of AZD2389 by assessment of inhibition of FAP activity in plasma after single oral dose of AZD2389 alone or in combination with itraconazole.	Day 1 to Day 8
Number of participants with Adverse Events (AEs)	To assess the safety and tolerability of a single oral dose of AZD2389 alone or in combination with itraconazole in healthy participants.	From Screening (Day -29 to Day -2) up to 8 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2025
• Primary Completion (Actual): April 23, 2025
• Study Completion (Actual): April 23, 2025

Study Registration Dates

• First Submitted: February 21, 2025
• First Submitted That Met QC Criteria: February 21, 2025
• First Posted (Actual): February 26, 2025

Study Record Updates

• Last Update Posted (Actual): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Chronic liver disease; Fibroblast Activation Protein inhibitor; Advanced hepatic fibrosis
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP3A Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: D7930C00005

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 Vivli.org. 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 approved.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA 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 anonymized individual patient-level data via secure research environmentVivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

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