Hepatic Impairment
Conditions
Keywords
Hepatic Impairment, Healthy participants, AZD5004, Pharmacokinetics, Safety
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.
Interventions
DRUGAZD5004
Dose 1
Sponsors
Fortrea Clinical Research Unit Inc.
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUCinf | Day 1 to Day 6 | Area under plasma concentration-time curve from zero to infinity |
| Cmax | Day 1 to Day 6 | Maximum observed plasma concentration |
| AUClast | Day 1 to Day 6 | Area under plasma concentration-time curve from time zero to the last measurable concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters (t1/2λz) | Day 1 to Day 6 | Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve |
| Tmax | Day 1 to Day 6 | Time to reach maximum observed plasma concentration |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with abnormal laboratory tests results | Day 1 to Day 6 | 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 |
| Participants with abnormal ECG QTcF findings | Day 1 to Day 6 | 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 |
| Participants with abnormal physical examination findings | Day 1 to Day 6 | 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 |
| Participants with abnormal heart rate | Day 1 to Day 6 | 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 |
| Number of participants with abnormal ECG PR interval findings | Day 1 to Day 6 | 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 |
| Participants with abnormal blood pressure | Day 1 to Day 6 | 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 |
| Number of participants with adverse events (AEs) | Day 1 to Day 10 | 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 |
| Number of participants with serious adverse events (SAEs) | Day 1 to Day 10 | 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 |
Countries
United States
Outcome results
None listed