A Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD2389

Phase 1

Recruiting

• Conditions: Hepatic Impairment
• Interventions: Drug: AZD2389

• Registration Number: NCT06812780
• Lead Sponsor: AstraZeneca

Brief Summary

The purpose of this study is to examine the safety and tolerability of AZD2389 in participants with hepatic impairment and participants with normal hepatic function.

Detailed Description

This is a single-dose, non-randomised, open-label, parallel-group study to examine the PK, fibroblast activation protein activity, safety, and tolerability of AZD2389 in participants with hepatic impairment and participants with normal hepatic function.

The study is planned to consist of:

* Cohort 1: Participants with normal hepatic function (sex-, age-, and body mass index \[BMI\]-matched)

* Cohort 2: Participants with mild hepatic impairment (CP A classification)

* Cohort 3: Participants with moderate hepatic impairment (CP B classification)

* Cohort 4 (Optional): Participants with severe hepatic impairment (CP C classification)

Safety, tolerability, and available plasma PK data up to 48 hours post-dose from at least 4 participants in each of the mild hepatic impairment (CP Class A) and moderate hepatic impairment (CP Class B) cohorts must have been assessed by the investigator(s), medical monitor, and sponsor prior to the decision to proceed with evaluation/recruitment of participants with severe hepatic impairment (CP Class C). Cohort 1 (normal hepatic function) will be initiated in parallel with Cohorts 2 and 3.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-03
• Study First Submitted QC: 2025-02-03
• Study Start: 2025-02-04
• Study First Posted: 2025-02-06
• Last Update Submitted: 2025-02-17
• Last Update Posted: 2025-02-19
• Primary Completion: 2025-12-16
• Study Completion: 2025-12-16

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

For Hepatic:

• Participant with a diagnosis of stable hepatic impairment

For Healthy:

• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests.

All participants:

• Body weight ≥ 50 kg; BMI within the range of 18.0 to 42.0 kg/m2 (inclusive).

Exclusion Criteria

• Participant has eGFR < 60 mL/minute/1.73 m2
• Positive test for HIV at screening
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity
• History of severe dermatological disorders

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1	AZD2389	Participants with normal hepatic function (sex-, age-, and body mass index \[BMI\]-matched)
Cohort 2	AZD2389	Participants with mild hepatic impairment (CP A classification)
Cohort 3	AZD2389	Participants with moderate hepatic impairment (CP B classification)
Cohort 4	AZD2389	Participants with severe hepatic impairment (CP C classification)

Primary Outcome Measures

Name	Time	Method
Plasma PK parameter Cmax	pre-dose to 48 hours post-dose	maximum observed plasma concentration
Plasma PK parameter AUCinf	pre-dose to 48 hours post-dose	area under the concentration-time curve from zero to infinity
Plasma PK parameter AUClast	pre-dose to 48 hours post-dose	area under the concentration-time curve from zero to the last measurable concentration

Secondary Outcome Measures

Name	Time	Method
Urine PK parameter CLr	pre-dose to 48 hours post-dose	renal clearance of the drug from plasma
Plasma PK parameter Vz/F	pre-dose to 48 hours post-dose	apparent volume of distribution during the terminal phase after extravascular administration.
Plasma PK parameter t1/2λz	pre-dose to 48 hours post-dose	half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve
Urine PK parameter Ae(t1-t2)	pre-dose to 48 hours post-dose	cumulative amount of unchanged drug excreted into the urine for the interval between time 1 and time 2
Plasma PK parameter Tmax	pre-dose to 48 hours post-dose	time to reach maximum observed plasma concentration
Plasma PK parameter CL/F	pre-dose to 48 hours post-dose	apparent total body clearance of drug from plasma after extravascular administration
Urine PK parameters fe(t1-t2)	pre-dose to 48 hours post-dose	fraction of the drug excreted into the urine for the interval between time 1 and time 2

Trial Locations

Locations (1)

Research Site; 🇺🇸 San Antonio, Texas, United States