Overview
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.
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
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.