Clinical trial NCT06813781: Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD5004
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Hepatic Impairment
Healthy participants
AZD5004
Pharmacokinetics
Safety
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Fortrea Clinical Research Unit Inc.
First posted: 2025-02-07
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Up to four groups (three hepatic impairment groups and controls with normal hepatic function) will be enrolled into this study.

All participants will receive the study intervention:

* Cohort 1 will enroll 8 participants with mild hepatic impairment
* Cohort 2 will enroll 8 participants with moderate hepatic impairment
* Cohort 3 will enroll 6-8 participants with severe hepatic impairment
* Cohort 4 will enroll \~8 participants with normal hepatic function matched by sex, age, and body weight
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: AUCinf
timeFrame: Day 1 to Day 6
measure: AUClast
timeFrame: Day 1 to Day 6
measure: Cmax
timeFrame: Day 1 to Day 6
Secondary outcomes:
measure: Tmax
timeFrame: Day 1 to Day 6
measure: PK parameters (t1/2λz)
timeFrame: Day 1 to Day 6
measure: PK parameters CL/F
timeFrame: Day 1 to Day 6
measure: PK parameters CLNR/F
timeFrame: Day 1 to Day 6
measure: PK parameter Vz/F
timeFrame: Day 1 to Day 6
measure: PK parameter CLr
timeFrame: Day 1 to Day 6
measure: PK parameter Ae
timeFrame: Day 1 to Day 6
measure: fe
timeFrame: Day 1 to Day 6
Other outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Day 1 to Day 10
measure: Participants with abnormal blood pressure
timeFrame: Day 1 to Day 6
measure: Number of participants with abnormal laboratory tests results
timeFrame: Day 1 to Day 6
measure: Number of participants with serious adverse events (SAEs)
timeFrame: Day 1 to Day 10
measure: Participants with abnormal ECG QTcF findings
timeFrame: Day 1 to Day 6
measure: Participants with abnormal physical examination findings
timeFrame: Day 1 to Day 6
measure: Participants with abnormal heart rate
timeFrame: Day 1 to Day 6
measure: Number of participants with abnormal ECG PR interval findings
timeFrame: Day 1 to Day 6
Locations:
city: Lake Forest
country: United States
facility: Research Site
state: California
city: Rialto
country: United States
facility: Research Site
state: California
city: Orlando
country: United States
facility: Research Site
state: Florida
city: San Antonio
country: United States
facility: Research Site
state: Texas
Study officials:
References: