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

Hepatic Impairment Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05919069
• Other study ID #: D7830C00008
• Status: Recruiting
• Phase: Phase 1
• Start date: June 16, 2023
• Est. completion date: September 9, 2024

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment

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 information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: September 9, 2024
• Est. primary completion date: September 9, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• AZD2693
Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment

Locations

Country	Name	City	State
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Orlando	Florida
United States	Research Site	Rialto	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK parameters AUCinf	area under the concentration-time curve (AUC) from zero to infinity (AUCinf)	85 days
Primary	PK parameters AUClast	area under the concentration-time curve from time zero to last time of quantifiable concentration	85 days
Primary	PK parameters Cmax	maximum observed plasma concentration	85 days
Secondary	PK parameters tmax	tmax: time to maximum observed plasma concentration	85 days
Secondary	PK parameters tlast	tlast: time of the last measurable concentration	85 days
Secondary	PK parameters t1/2?z	apparent terminal elimination half-life	85 days
Secondary	PK parameters CL/F	CL/F: apparent clearance	85 days
Secondary	PK Parameters Vz/F	Vz/F: apparent volume of distribution based on terminal phase	85 days
Secondary	PK parameters CLR	CLR: Renal clearance of drug from plasma	85 days
Secondary	PK parameters fe	fe: Percentage of dose excreted unchanged in urine	85 days
Secondary	PK parameters Ae	Amount of unchanged drug excreted into urine	85 days