Hepatic Impairment
Conditions
Keywords
Mild, Moderate, Severe, Healthy Matches
Brief summary
Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment
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 AZD2693 administered as an subcutaneous injection in male and female participants with mild, moderate, or severe hepatic impairment compared with male and female participants with normal hepatic function (as control). Eight participants with mild impairment (CP Class A); 8 participants with moderate impairment (CP Class B); 8 participants with severe impairment (CP Class C); and 8 to12 participants with normal hepatic function matched on a group level regarding age, body weight, and sex to the impaired participants are planned for study intervention with the goal of having at least 6 evaluable participants within each group. Study participants who self-withdraw after study intervention may be replaced to ensure that at least 6 participants per group are evaluable and complete the study per protocol. An evaluable participant is defined as having adequate plasma PK profile to meet the primary study objective. Child-Pugh scoring, detailed in Table 2, will be used to determine the level of hepatic impairment. Participants will be enrolled into the following groups based on their CP classification score as determined at screening: Group 1: Participants with mild hepatic impairment (CP Class A, score of 5 or 6). Group 2: Participants with moderate hepatic impairment (CP Class B, score of 7 to 9). Group 3: Participants with severe hepatic impairment (CP Class C, score of 10 to 15). Group 4: Participants with normal hepatic function. Study Arms and Duration: * Planned screening duration per participant: up to 4 weeks. * Planned study duration (screening to follow-up) per participant: up to 16 weeks.
Interventions
DRUGAZD2693
Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment
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: Group 1: Participants with mild hepatic impairment (CP Class A, score of 5 or 6). Group 2: Participants with moderate hepatic impairment (CP Class B, score of 7 to 9). Group 3: Participants with severe hepatic impairment (CP Class C, score of 10 to 15). Group 4: Participants with normal hepatic function matched on a group level regarding age, body weight, and sex to the impaired groups
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
For Hepatic: * Participant with a diagnosis of chronic and stable hepatic impairment For Healthy: * Participant with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or 12-lead ECGs, All participants: \- Body weight ≥ 50 kg; BMI within the range of 18.0 to 40.0 kg/m2 (inclusive) as measured at screening
Exclusion criteria
* Participant with impaired hepatic function has eGFR \< 60 mL/minute/1.73 m2 and participant with normal hepatic function has eGFR \< 90 mL/minute/1.73 m2 * Positive test for HIV at screening * History or presence of clinically significant thyroid disease * History or presence of clinically significant or unstable medical or psychiatric condition * History of any major surgical procedure within 30 days prior to study intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters AUClast | 85 days | area under the concentration-time curve from time zero to last time of quantifiable concentration |
| PK parameters Cmax | 85 days | maximum observed plasma concentration |
| PK parameters AUCinf | 85 days | area under the concentration-time curve (AUC) from zero to infinity (AUCinf) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters tlast | 85 days | tlast: time of the last measurable concentration |
| PK parameters t1/2λz | 85 days | apparent terminal elimination half-life |
| PK parameters CL/F | 85 days | CL/F: apparent clearance |
| PK Parameters Vz/F | 85 days | Vz/F: apparent volume of distribution based on terminal phase |
| PK parameters CLR | 85 days | CLR: Renal clearance of drug from plasma |
| PK parameters fe | 85 days | fe: Percentage of dose excreted unchanged in urine |
| PK parameters Ae | 85 days | Amount of unchanged drug excreted into urine |
| PK parameters tmax | 85 days | tmax: time to maximum observed plasma concentration |
Countries
United States
Outcome results
None listed