A Phase I Study to Investigate the Effect of Hepatic Impairment on the PK, Safety, and Tolerability of AZD2693

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment

Treatments: Drug: AZD2693

Study type: Interventional

Funder types: Industry

Identifiers

NCT05919069

D7830C00008

Details and patient eligibility

About

Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment

Full 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.

Enrollment: 35 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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35 participants in 4 patient groups

Group 1

Experimental group

Description:

Participants with mild hepatic impairment (CP Class A, score of 5 or 6)

Treatment:

Drug: AZD2693

Group 2

Experimental group

Description:

Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)

Treatment:

Drug: AZD2693

Group 3

Experimental group

Description:

Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Treatment:

Drug: AZD2693

Group 4

Experimental group

Description:

Participants with normal hepatic function matched on a group level regarding age, body weight, and sex to the impaired groups

Treatment:

Drug: AZD2693