A Phase I Study to Investigate the Effect of Hepatic Impairment on the PK, Safety, and Tolerability of AZD2693
- Registration Number
- NCT05919069
- Lead Sponsor
- AstraZeneca
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 4 AZD2693 Participants with normal hepatic function matched on a group level regarding age, body weight, and sex to the impaired groups Group 3 AZD2693 Participants with severe hepatic impairment (CP Class C, score of 10 to 15) Group 2 AZD2693 Participants with moderate hepatic impairment (CP Class B, score of 7 to 9) Group 1 AZD2693 Participants with mild hepatic impairment (CP Class A, score of 5 or 6)
- Primary Outcome Measures
Name Time Method PK parameters AUCinf 85 days area under the concentration-time curve (AUC) from zero to infinity (AUCinf)
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
- Secondary Outcome Measures
Name Time Method PK parameters fe 85 days fe: Percentage of dose excreted unchanged in urine
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 Vz/F 85 days Vz/F: apparent volume of distribution based on terminal phase
PK parameters Ae 85 days Amount of unchanged drug excreted into urine
PK parameters tmax 85 days tmax: time to maximum observed plasma concentration
PK parameters CL/F 85 days CL/F: apparent clearance
PK parameters CLR 85 days CLR: Renal clearance of drug from plasma
Trial Locations
- Locations (1)
Research Site
🇺🇸Orlando, Florida, United States