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

Phase 1

Completed

• Conditions: Healthy Participants
• Interventions: Drug: AZD2389; Drug: Itraconazole

• Registration Number: NCT06846528
• Lead Sponsor: AstraZeneca

Brief Summary

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

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 Timeline

• Study First Submitted: 2025-02-21
• Study First Submitted QC: 2025-02-21
• Study Start: 2025-02-26
• Study First Posted: 2025-02-26
• Status Verified: 2025-04
• Primary Completion: 2025-04-23
• Study Completion: 2025-04-23
• Last Update Submitted: 2025-04-28
• Last Update Posted: 2025-04-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
AZD2389 and Itraconazole	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.
AZD2389 and Itraconazole	AZD2389	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Research Site; 🇺🇸 Brooklyn, Maryland, United States