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

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.

Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: AZD2693

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Rialto, California, United States, 92377
      • Research Site
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Research Site
    • Orlando, Florida, United States, 32808
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Participants with mild hepatic impairment (CP Class A, score of 5 or 6)	Drug: AZD2693; Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment
Experimental: Group 2; Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)	Drug: AZD2693; Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment
Experimental: Group 3; Participants with severe hepatic impairment (CP Class C, score of 10 to 15)	Drug: AZD2693; Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment
Experimental: Group 4; Participants with normal hepatic function matched on a group level regarding age, body weight, and sex to the impaired groups	Drug: AZD2693; Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters AUCinf	area under the concentration-time curve (AUC) from zero to infinity (AUCinf)	85 days
PK parameters AUClast	area under the concentration-time curve from time zero to last time of quantifiable concentration	85 days
PK parameters Cmax	maximum observed plasma concentration	85 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters tmax	tmax: time to maximum observed plasma concentration	85 days
PK parameters tlast	tlast: time of the last measurable concentration	85 days
PK parameters t1/2λz	apparent terminal elimination half-life	85 days
PK parameters CL/F	CL/F: apparent clearance	85 days
PK Parameters Vz/F	Vz/F: apparent volume of distribution based on terminal phase	85 days
PK parameters CLR	CLR: Renal clearance of drug from plasma	85 days
PK parameters fe	fe: Percentage of dose excreted unchanged in urine	85 days
PK parameters Ae	Amount of unchanged drug excreted into urine	85 days

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• Redacted CSR Synopsis
• AZCT

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2023
• Primary Completion (Actual): September 16, 2024
• Study Completion (Actual): September 16, 2024

Study Registration Dates

• First Submitted: June 16, 2023
• First Submitted That Met QC Criteria: June 16, 2023
• First Posted (Actual): June 26, 2023

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Severe; Moderate; Mild; Healthy Matches
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Follicular
• Other Study ID Numbers: D7830C00008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No