Hepatic Impairment
Conditions
Keywords
Mild, Moderate, Severe, Matched Healthy Controls, Liver Fibrosis, Liver Cirrhosis
Brief summary
The purpose of this study is to examine the safety and tolerability of AZD2389 in participants with hepatic impairment and participants with normal hepatic function.
Detailed description
This is a single-dose, non-randomised, open-label, parallel-group study to examine the PK, fibroblast activation protein activity, safety, and tolerability of AZD2389 in participants with hepatic impairment and participants with normal hepatic function. The study is planned to consist of: * Cohort 1: Participants with normal hepatic function (sex-, age-, and body mass index \[BMI\]-matched) * Cohort 2: Participants with mild hepatic impairment (CP A classification) * Cohort 3: Participants with moderate hepatic impairment (CP B classification) * Cohort 4 (Optional): Participants with severe hepatic impairment (CP C classification) Safety, tolerability, and available plasma PK data up to 48 hours post-dose from at least 4 participants in each of the mild hepatic impairment (CP Class A) and moderate hepatic impairment (CP Class B) cohorts must have been assessed by the investigator(s), medical monitor, and sponsor prior to the decision to proceed with evaluation/recruitment of participants with severe hepatic impairment (CP Class C). Cohort 1 (normal hepatic function) will be initiated in parallel with Cohorts 2 and 3.
Interventions
DRUGAZD2389
Single oral dose of AZD2389 in participants from all cohorts
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Participants will be enrolled within the following groups based on their CP classification score as determined at screening: Cohort 1: Participants with normal hepatic function (sex-, age-, and body mass index \[BMI\]-matched) * Cohort 2: Participants with mild hepatic impairment (CP A classification) * Cohort 3: Participants with moderate hepatic impairment (CP B classification) * Cohort 4 (Optional): Participants with severe hepatic impairment (CP C classification)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
For Hepatic: * Participant with a diagnosis of stable hepatic impairment For Healthy: * Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests. All participants: \- Body weight ≥ 50 kg; BMI within the range of 18.0 to 42.0 kg/m2 (inclusive).
Exclusion criteria
* Participant has eGFR \< 60 mL/minute/1.73 m2 * Positive test for HIV at screening * History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity * History of severe dermatological disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma PK parameter Cmax | pre-dose to 48 hours post-dose | maximum observed plasma concentration |
| Plasma PK parameter AUCinf | pre-dose to 48 hours post-dose | area under the concentration-time curve from zero to infinity |
| Plasma PK parameter AUClast | pre-dose to 48 hours post-dose | area under the concentration-time curve from zero to the last measurable concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma PK parameter Vz/F | pre-dose to 48 hours post-dose | apparent volume of distribution during the terminal phase after extravascular administration. |
| Urine PK parameter Ae(t1-t2) | pre-dose to 48 hours post-dose | cumulative amount of unchanged drug excreted into the urine for the interval between time 1 and time 2 |
| Plasma PK parameter t1/2λz | pre-dose to 48 hours post-dose | half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve |
| Urine PK parameters fe(t1-t2) | pre-dose to 48 hours post-dose | fraction of the drug excreted into the urine for the interval between time 1 and time 2 |
| Urine PK parameter CLr | pre-dose to 48 hours post-dose | renal clearance of the drug from plasma |
| Plasma PK parameter Tmax | pre-dose to 48 hours post-dose | time to reach maximum observed plasma concentration |
| Plasma PK parameter CL/F | pre-dose to 48 hours post-dose | apparent total body clearance of drug from plasma after extravascular administration |
Countries
United States
Outcome results
None listed