A Phase I Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD4144

A Phase I, Multicentre, Single-Dose, Non-Randomised, Open-Label, Parallel-Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD4144

This Phase I, open-label, parallel group study will investigate the single oral dose PK, safety, and tolerability of AZD4144 to male and female participants with mild, moderate, and severe hepatic impairment compared to matched controls with normal hepatic function.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: AZD4144

Detailed Description

This Phase I, open-label, parallel group study will investigate the single oral dose PK, safety, and tolerability of AZD4144 to male and female participants with mild, moderate, and severe hepatic impairment compared to matched controls with normal hepatic function.

Approximately 60 participants are planned to be screened to achieve up to 30 evaluable participants. For each of the 3 hepatic impairment groups, 6 participants are planned to complete the study. Initially, 6 participants with normal hepatic function will be recruited, matched on a group level regarding sex, age, and BMI to the participants with hepatic impairment. Additional participants with normal hepatic function, up to a total of 12, may be included if needed to meet the matching criteria.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85210
      • Research Site
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Research Site
    • Orlando, Florida, United States, 32809
      • Research Site
  • Texas
    • Austin, Texas, United States, 78757
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Healthy Matched Control Participants Only (Group 4):

• Must be medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1.

Hepatically-Impaired Participants Only (Groups 1, 2, and 3):

• Must have a diagnosis of chronic (≥ 6 months) and stable hepatic impairment (e.g., no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status within 30 days prior to study screening, as determined by the investigator at screening and Day -1).
• Must be classified by the investigator as CP Class A (Group 1), CP Class B (Group 2), or CP Class C (Group 3) at screening.
• Participant must be stable on a concomitant medication and/or treatment regimen (defined as not starting a new treatment/medication[s] or a change in the dosage or frequency of the concomitant medication[s] within at least 2 weeks prior to screening).

All Groups:

• Body weight ≥ 50 kg and body mass index (BMI) within the range 18 to 45 kg/m2, inclusive.
• All Females of Childbearing Potential (FOCBP) must have a negative pregnancy test at screening and Day -1.

Exclusion Criteria:

• History of any clinically significant 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.
• Have Type 1 diabetes mellitus or T2DM (Group 4)
• Known history of primary immunodeficiency (congenital or acquired) or an underlying condition that predisposes to infection.
• History of long QT syndrome or prolonged QTcF.
• Presence of unstable medical or psychological conditions, or any evidence of additional severe or uncontrolled systemic disease (e.g., currently unstable or uncompensated renal, cardiovascular, or respiratory disease).
• Evidence of renal impairment at screening
• Current liver transplant or anticipated to receive liver transplant within 2 months of screening or Day -1 (Group 1, 2 and 3).
• Use of any of the prescription and non-prescription prohibited medications.
• Concomitant immunosuppressive, steroid treatment.
• Live or attenuated vaccines within 3 months prior to study intervention or live vaccinations planned during the trial.
• History of severe allergy/hypersensitivity of AZD4144 or any of the excipients of the product.
• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days prior to study intervention in this study or, if known, 5 half-lives from last dose in the previous study to study intervention in this study, whichever is longest.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Participants with mild hepatic impairment (CP Class A, score of 5 or 6)	Drug: AZD4144; Single oral dose of AZD4144 in participants from all groups
Experimental: Group 2; Participants with moderate hepatic impairment (CP Class B, score of 7 to 9).	Drug: AZD4144; Single oral dose of AZD4144 in participants from all groups
Experimental: Group 3; Participants with severe hepatic impairment (CP Class C, score of 10 to 15).	Drug: AZD4144; Single oral dose of AZD4144 in participants from all groups
Experimental: Group 4; Participants with normal hepatic function matched on a group level regarding sex, age, and BMI to the impaired groups	Drug: AZD4144; Single oral dose of AZD4144 in participants from all groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters AUCinf	area under the concentration-time curve from zero to infinity	Day 0 through Day 7 or 9
PK parameter AUClast	area under the concentration-time curve from zero to the last measurable concentration	Day 0 through Day 7 or 9
PK parameters AUC(0-144)	area under the curve from time zero to time 144hours post dose	Day 0 through Day 7
PK parameter Cmax	maximum observed plasma concentration	Day 0 through Day 7 or 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters tmax	time to reach maximum observed plasma concentration	Day 0 through Day 7 or 9
PK Parameters t1/2λz	half-life associated with terminal slope (λz)	Day 0 through Day 7 or 9
PK Parameters CL/F	apparent total body clearance of drug from plasma after extravascular administration	Day 0 through Day 7 or 9
PK Parameters Vz/F	apparent volume of distribution during the terminal phase after extravascular administration.	Day 0 through Day 7 or 9
PK Parameters CLNR/F	non-renal clearance of drug from plasma	Day 0 through Day 7 or 9
PK parameters CLR from urine concentrations	renal clearance from urine concentration	Day 0 through Day 3
PK parameters Ae determined from urine concentration	amount of unchanged drug excreted into the urine	Day 0 through Day 3
PK parameters fe determined from urine concentration	Percentage of unchanged drug excreted into the urine	Day 0 through Day 3
PK Parameters tlast	time of last quantifiable concentration	Day 0 through Day 7 or 9
PK Parameters λz	terminal elimination rate constant	Day 0 through Day 7 or 9
PK Parameters AUC(0-24)	area under the plasma concentration-time curve from time 0 to 24 hours postdose	Day 0 through Day 1
PK Parameters AUC(0-72)	area under the plasma concentration-time curve from time 0 to 72 hours postdose	Day 0 through Day 3

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Estimated): August 24, 2026
• Primary Completion (Estimated): May 28, 2027
• Study Completion (Estimated): May 28, 2027

Study Registration Dates

• First Submitted: August 20, 2026
• First Submitted That Met QC Criteria: August 20, 2026
• First Posted (Actual): August 24, 2026

Study Record Updates

• Last Update Posted (Actual): August 24, 2026
• Last Update Submitted That Met QC Criteria: August 20, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Hepatic Impairment; Moderate hepatic impairment; Mild hepatic impairment; Severe hepatic impairment; Matched Healthy normal; AZD4144
• Other Study ID Numbers: D9441C00007

Drug and device information, study documents

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