Clinical trial NCT05919069: A Phase I Study to Investigate the Effect of Hepatic Impairment on the PK, Safety, and Tolerability of AZD2693
Official title: A Single Dose, Non-Randomised, Open-Label, Parallel Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of AZD2693
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Mild
Moderate
Severe
Healthy Matches
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-06-26
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: PK parameters AUCinf
timeFrame: 85 days
measure: PK parameters AUClast
timeFrame: 85 days
measure: PK parameters Cmax
timeFrame: 85 days
Secondary outcomes:
measure: PK parameters tmax
timeFrame: 85 days
measure: PK parameters tlast
timeFrame: 85 days
measure: PK parameters t1/2λz
timeFrame: 85 days
measure: PK parameters CL/F
timeFrame: 85 days
measure: PK Parameters Vz/F
timeFrame: 85 days
measure: PK parameters CLR
timeFrame: 85 days
measure: PK parameters fe
timeFrame: 85 days
measure: PK parameters Ae
timeFrame: 85 days
Other outcomes:
Locations:
city: Rialto
country: United States
facility: Research Site
state: California
city: Miami Lakes
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
Study officials:
References: