Investigating how liver impairment affects the drug 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 study is testing how well the drug AZD5004 works and is tolerated in people with liver problems compared to healthy individuals.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: AstraZeneca (Industry-sponsored)
• Locations: 4 sites (Lake Forest, California and 3 other locations)
• Trial ID: NCT06813781 on ClinicalTrials.gov

What this trial studies

This Phase I, multicentre, open-label study aims to evaluate the pharmacokinetics, safety, and tolerability of AZD5004 in participants with varying degrees of hepatic impairment compared to healthy individuals. Participants will be grouped based on their Child Pugh classification, which assesses the severity of liver disease. The study will involve a single dose of AZD5004 and will include both male and female participants aged 18 to 80. The goal is to understand how liver function impacts the drug's behavior in the body.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-80 with mild, moderate, or severe hepatic impairment as classified by the Child Pugh score.

Not a fit: Patients with acute liver failure or those with uncontrolled medical conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide critical insights into the safe use of AZD5004 in patients with liver impairment.

How similar studies have performed: Other studies have shown success in evaluating drug pharmacokinetics in patients with hepatic impairment, making this approach well-established.

Eligibility criteria

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.

Where this trial is running

Lake Forest, California and 3 other locations

• Research Site — Lake Forest, California, United States (Recruiting)
• Research Site — Rialto, California, United States (Recruiting)
• Research Site — Orlando, Florida, United States (Recruiting)
• Research Site — San Antonio, Texas, United States (Recruiting)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions Hepatic Impairment; Healthy participants; AZD5004; Pharmacokinetics; Safety