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

Phase 1

Recruiting

• Conditions: Hepatic Impairment
• Interventions: Drug: AZD5004

• Registration Number: NCT06813781
• Lead Sponsor: AstraZeneca

Brief Summary

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.

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 Timeline

• Study First Submitted: 2024-12-17
• Study Start: 2024-12-19
• Study First Submitted QC: 2025-02-04
• Study First Posted: 2025-02-07
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-15
• Last Update Posted: 2025-05-16
• Primary Completion: 2025-10-21
• Study Completion: 2025-10-21

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 32

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 4	AZD5004	A single oral dose of AZD5004 under fasted conditions.
Group 1	AZD5004	A single oral dose of AZD5004 under fasted conditions.
Group 2	AZD5004	A single oral dose of AZD5004 under fasted conditions.
Group 3	AZD5004	A single oral dose of AZD5004 under fasted conditions.

Primary Outcome Measures

Name	Time	Method
AUCinf	Day 1 to Day 6	Area under plasma concentration-time curve from zero to infinity
AUClast	Day 1 to Day 6	Area under plasma concentration-time curve from time zero to the last measurable concentration
Cmax	Day 1 to Day 6	Maximum observed plasma concentration

Secondary Outcome Measures

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

Trial Locations

Locations (1)

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