Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD5004

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 AZD5004

This is a Phase I, multicentre, single-dose, non-randomised, open-label, parallel-group study to examine the PK, safety, and tolerability of AZD5004 in male and female participants with mild, moderate, and severe hepatic impairment compared with participants with normal hepatic function.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: AZD5004

Detailed Description

This is a Phase I, multicentre, single-dose, non-randomised, open-label, parallel-group study to examine the PK, safety, and tolerability of AZD5004 in male and female participants with mild, moderate, or severe hepatic impairment compared with participants with normal hepatic function.

Participants will be enrolled within the following groups based on their Child Pugh classification score as determined at screening:

Group 1: Participants with mild hepatic impairment (Child Pugh Class A, score of 5 or 6).

Group 2: Participants with moderate hepatic impairment (Child Pugh Class B, score of 7 to 9).

Group 3: Participants with severe hepatic impairment (Child Pugh Class C, score of 10 to 15).

Group 4: Participants with normal hepatic function matched on a group level regarding sex, age, and body weight to the impaired participants.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Lake Forest, California, United States, 92630
      • Research Site
    • Rialto, California, United States, 92377
      • Research Site
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Research Site
    • Orlando, Florida, United States, 32809
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78215
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

For ALL participants:

• Adults 18-80 years of age
• Weight ≥50kg and BMI between ≥18 to ≤40 kg/m2 For participants with normal hepatic function:
• Participant must be stable on a concomitant medication and/or treatment regimen for at least 2 weeks prior to screening

For Healthy Controls:

-Participant must be medically healthy with no significant findings on medical evaluation at screening to include but not limited to an eGFR >90 ml/min/1.73 m2

For participants with hepatic impairment:

• Group 1 (mild) must have an Child-Pugh score of 5 or 6, Group 2 (moderate) must have a Child-Pugh score of 7 to 9, Group 3 (severe) must have a Child-Pugh score of 10 to 15.
• Participant must have a diagnosis of chronic (≥ 6 months) and stable hepatic impairment (eg, no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status within 30 days prior to study screening

Exclusion Criteria:

For ALL participants:

• Poorly controlled diabetes mellitus (A1C >10% at screening).
• Unwillingness to use adequate contraception
• Uncontrolled hypertension or hypotension
• Presence of unstable systemic disease or psychologic conditions.
• Any clinically significant abnormalities in rhythm, conduction, or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG.

Specific For Healthy Controls:

-Positive screening for HIV, Hepatitis B, or Hepatitis C -

-Any clinically significant disease or disorder to include but not limited to acute or chronic liver disease

Specific For Hepatically Impaired Participants:

• eGFR <60 ml/min/1.73 m2
• Fluctuating or rapidly deteriorating hepatic function, as indicated by strongly varying or worsening of clinical and/or laboratory signs of hepatic impairment to include rising LFTs, paracentesis at less than 4 week intervals, oesophageal banding within the last 3 months, or treatment for GI bleeding within the last 6 months
• Presence of a hepatocellular carcinoma or acute liver disease caused by an infection or drug toxicity.

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; A single oral dose of AZD5004 under fasted conditions.	Drug: AZD5004; Dose 1; Other Names: Dose 1; ECC5004
Experimental: Group 2; A single oral dose of AZD5004 under fasted conditions.	Drug: AZD5004; Dose 1; Other Names: Dose 1; ECC5004
Experimental: Group 3; A single oral dose of AZD5004 under fasted conditions.	Drug: AZD5004; Dose 1; Other Names: Dose 1; ECC5004
Experimental: Group 4; A single oral dose of AZD5004 under fasted conditions.	Drug: AZD5004; Dose 1; Other Names: Dose 1; ECC5004

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCinf	Area under plasma concentration-time curve from zero to infinity	Day 1 to Day 6
AUClast	Area under plasma concentration-time curve from time zero to the last measurable concentration	Day 1 to Day 6
Cmax	Maximum observed plasma concentration	Day 1 to Day 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	Time to reach maximum observed plasma concentration	Day 1 to Day 6
PK parameters (t1/2λz)	Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve	Day 1 to Day 6
PK parameters CL/F	Apparent total body clearance of drug from plasma after extravascular administration	Day 1 to Day 6
PK parameters CLNR/F	Non-renal clearance of drug from plasma after oral administration	Day 1 to Day 6
PK parameter Vz/F	Apparent volume of distribution during the terminal phase after extravascular administration	Day 1 to Day 6
PK parameter CLr	Renal clearance of the drug from plasma	Day 1 to Day 6
PK parameter Ae	Cumulative amount of unchanged drug excreted into the urine	Day 1 to Day 6
fe	Fraction of the drug excreted into the urine	Day 1 to Day 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	To assess the safety and tolerability of a single oral dose of AZD5004 for participants with mild, moderate, and severe hepatic impairment and those with normal hepatic function	Day 1 to Day 10
Participants with abnormal blood pressure	To assess the safety and tolerability of a single oral dose of AZD5004 for participants with mild, moderate, and severe hepatic impairment and those with normal hepatic function	Day 1 to Day 6
Number of participants with abnormal laboratory tests results	To assess the safety and tolerability of a single oral dose of AZD5004 for participants with mild, moderate, and severe hepatic impairment and those with normal hepatic function	Day 1 to Day 6
Number of participants with serious adverse events (SAEs)	To assess the safety and tolerability of a single oral dose of AZD5004 for participants with mild, moderate, and severe hepatic impairment and those with normal hepatic function	Day 1 to Day 10
Participants with abnormal ECG QTcF findings	To assess the safety and tolerability of a single oral dose of AZD5004 for participants with mild, moderate, and severe hepatic impairment and those with normal hepatic function	Day 1 to Day 6
Participants with abnormal physical examination findings	To assess the safety and tolerability of a single oral dose of AZD5004 for participants with mild, moderate, and severe hepatic impairment and those with normal hepatic function	Day 1 to Day 6
Participants with abnormal heart rate	To assess the safety and tolerability of a single oral dose of AZD5004 for participants with mild, moderate, and severe hepatic impairment and those with normal hepatic function	Day 1 to Day 6
Number of participants with abnormal ECG PR interval findings	To assess the safety and tolerability of a single oral dose of AZD5004 for participants with mild, moderate, and severe hepatic impairment and those with normal hepatic function	Day 1 to Day 6

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Fortrea Clinical Research Unit Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2024
• Primary Completion (Actual): October 2, 2025
• Study Completion (Actual): October 2, 2025

Study Registration Dates

• First Submitted: December 17, 2024
• First Submitted That Met QC Criteria: February 4, 2025
• First Posted (Actual): February 7, 2025

Study Record Updates

• Last Update Posted (Estimated): October 15, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Healthy participants; Hepatic Impairment; AZD5004
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: D7260C00011

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 de-identified 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