Hepatic Impairment
Conditions
Keywords
Hepatic Impairment, Mild hepatic impairment, Moderate hepatic impairment, Severe hepatic impairment, Matched Healthy normal, AZD4144
Brief summary
This Phase I, open-label, parallel group study will investigate the single oral dose PK, safety, and tolerability of AZD4144 to male and female participants with mild, moderate, and severe hepatic impairment compared to matched controls with normal hepatic function.
Detailed description
This Phase I, open-label, parallel group study will investigate the single oral dose PK, safety, and tolerability of AZD4144 to male and female participants with mild, moderate, and severe hepatic impairment compared to matched controls with normal hepatic function. Approximately 60 participants are planned to be screened to achieve up to 30 evaluable participants. For each of the 3 hepatic impairment groups, 6 participants are planned to complete the study. Initially, 6 participants with normal hepatic function will be recruited, matched on a group level regarding sex, age, and BMI to the participants with hepatic impairment. Additional participants with normal hepatic function, up to a total of 12, may be included if needed to meet the matching criteria.
Interventions
DRUGAZD4144
Single oral dose of AZD4144 in participants from all groups
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
No masking
Intervention model description
Participants will be enrolled into the following groups based on their Child-Pugh classification score as determined by a local laboratory 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 BMI to the impaired groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy Matched Control Participants Only (Group 4): • Must be medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1. Hepatically-Impaired Participants Only (Groups 1, 2, and 3): * Must have a diagnosis of chronic (≥ 6 months) and stable hepatic impairment (e.g., no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status within 30 days prior to study screening, as determined by the investigator at screening and Day -1). * Must be classified by the investigator as CP Class A (Group 1), CP Class B (Group 2), or CP Class C (Group 3) at screening. * Participant must be stable on a concomitant medication and/or treatment regimen (defined as not starting a new treatment/medication\[s\] or a change in the dosage or frequency of the concomitant medication\[s\] within at least 2 weeks prior to screening). All Groups: * Body weight ≥ 50 kg and body mass index (BMI) within the range 18 to 45 kg/m2, inclusive. * All Females of Childbearing Potential (FOCBP) must have a negative pregnancy test at screening and Day -1.
Exclusion criteria
* History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study. * Have Type 1 diabetes mellitus or T2DM (Group 4) * Known history of primary immunodeficiency (congenital or acquired) or an underlying condition that predisposes to infection. * History of long QT syndrome or prolonged QTcF. * Presence of unstable medical or psychological conditions, or any evidence of additional severe or uncontrolled systemic disease (e.g., currently unstable or uncompensated renal, cardiovascular, or respiratory disease). * Evidence of renal impairment at screening * Current liver transplant or anticipated to receive liver transplant within 2 months of screening or Day -1 (Group 1, 2 and 3). * Use of any of the prescription and non-prescription prohibited medications. * Concomitant immunosuppressive, steroid treatment. * Live or attenuated vaccines within 3 months prior to study intervention or live vaccinations planned during the trial. * History of severe allergy/hypersensitivity of AZD4144 or any of the excipients of the product. * Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days prior to study intervention in this study or, if known, 5 half-lives from last dose in the previous study to study intervention in this study, whichever is longest.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters AUCinf | Day 0 through Day 7 or 9 | area under the concentration-time curve from zero to infinity |
| PK parameter AUClast | Day 0 through Day 7 or 9 | area under the concentration-time curve from zero to the last measurable concentration |
| PK parameters AUC(0-144) | Day 0 through Day 7 | area under the curve from time zero to time 144hours post dose |
| PK parameter Cmax | Day 0 through Day 7 or 9 | maximum observed plasma concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters tmax | Day 0 through Day 7 or 9 | time to reach maximum observed plasma concentration |
| PK Parameters t1/2λz | Day 0 through Day 7 or 9 | half-life associated with terminal slope (λz) |
| PK Parameters CL/F | Day 0 through Day 7 or 9 | apparent total body clearance of drug from plasma after extravascular administration |
| PK Parameters Vz/F | Day 0 through Day 7 or 9 | apparent volume of distribution during the terminal phase after extravascular administration. |
| PK Parameters CLNR/F | Day 0 through Day 7 or 9 | non-renal clearance of drug from plasma |
| PK parameters CLR from urine concentrations | Day 0 through Day 3 | renal clearance from urine concentration |
| PK parameters Ae determined from urine concentration | Day 0 through Day 3 | amount of unchanged drug excreted into the urine |
| PK parameters fe determined from urine concentration | Day 0 through Day 3 | Percentage of unchanged drug excreted into the urine |
| PK Parameters tlast | Day 0 through Day 7 or 9 | time of last quantifiable concentration |
| PK Parameters λz | Day 0 through Day 7 or 9 | terminal elimination rate constant |
| PK Parameters AUC(0-24) | Day 0 through Day 1 | area under the plasma concentration-time curve from time 0 to 24 hours postdose |
| PK Parameters AUC(0-72) | Day 0 through Day 3 | area under the plasma concentration-time curve from time 0 to 72 hours postdose |
Countries
United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed