Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD0780

NCT06576765 | Completed Phase 1 FDA Drug

• 1 other identifier: D7960C00010
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

Brief Summary

This study will evaluate the pharmacokinetics (PK), safety, and tolerability of a single oral dose of AZD0780 with moderate and possibly mild hepatic impairment in comparison to a matched healthy control group.

Conditions

Hepatic Impairment

Keywords

Hepatic Impairment; Healthy participants; AZD0780; Pharmacokinetics; Safety

Outcome Measures

Primary Outcomes (3)

• AUClast

  Area under plasma concentration-time curve from time zero to the last measurable concentration

  Day 1 to Day 11

• AUCinf

  Area under plasma concentration-time curve from zero to infinity

  Day 1 to Day 11

• Cmax

  Maximum observed plasma concentration

  Day 1 to Day 11

Secondary Outcomes (11)

• Number of participants with adverse events (AEs)

  Day 1 to Day 11

• Number of participants with abnormal Vital signs, abnormal ECGs, and abnormal physical examination findings

  Day 1 to Day 11

• Number of participants with abnormal laboratory tests results

  Day 1 to Day 11

• Tmax

  Day 1 to Day 11

• PK parameters (t1/2λz)

  Day 1 to Day 11

Other Outcomes (1)

• Multi-omics Analysis

  Day 1

Study Arms (3)

Group 1

EXPERIMENTAL

Subjects with Moderate Impairment will receive a single oral dose of AZD0780 under fasted conditions.

Drug: AZD0780

Group 2

EXPERIMENTAL

Healthy participants will receive a single oral dose of AZD0780 under fasted conditions.

Drug: AZD0780

Group 3 (optional)

EXPERIMENTAL

Subjects with Mild Impairment will receive a single oral dose of AZD0780 under fasted conditions.

Drug: AZD0780

Interventions

AZD0780 DRUG

Dose 1

Also known as: Dose 1

Group 1; Group 2; Group 3 (optional)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 18 to 85 years of age, inclusive at screening
• For participants with normal hepatic function:
• Participant must be medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1.
• For participants with hepatic impairment:
• Participant must have a diagnosis of chronic (≥ 6 months) and stable hepatic impairment at screening and Day -1.
• Supporting documents confirming the participant's hepatic impairment must be available
• Participants must be stable on a concomitant medication and/or treatment regimen. Minor changes in dosage can be accepted at the discretion of the investigator.
• Male participants:
• Males must be surgically sterile or using, in conjunction with their female partner, a highly effective method of contraception for the duration of the study (from the time of study intervention administration) until 3 months after discharge to prevent pregnancy in a partner.
• Female participants of non-childbearing potential:
• Female participants must not be pregnant and must have a negative pregnancy test at screening and check-in, must not be lactating, and must not be of childbearing potential.

You may not qualify if:

• For participants with normal hepatic function:
• Any clinically significant disease or disorder (eg, cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal including bone fractures, endocrine including adrenal insufficiency, metabolic, malignant, psychiatric, major physical impairment)
• Use of any prescription or non-prescription drugs within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before study intervention, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study.
• For participants with hepatic impairment:
• Presence of unstable medical (eg, diabetes) or psychological conditions, or any evidence of additional severe or uncontrolled systemic disease (eg, currently unstable or uncompensated renal, cardiovascular, or respiratory disease) or laboratory finding which, in the opinion of the investigator, would compromise the participant's safety or successful participation in this study.
• Participant has evidence of hepatorenal syndrome or creatinine clearance \< 60 mL/minute as calculated using the Cockcroft-Gault equation.
• Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding (frequent bleeding gums or nose bleeds) at screening or Day -1.
• Fluctuating or rapidly deteriorating hepatic function, as indicated by strongly varying or worsening of clinical and/or laboratory signs of hepatic impairment within the screening period.
• Presence of a hepatocellular carcinoma or acute liver disease caused by an infection or drug toxicity.
• Hepatic impairment due to non-liver disease (eg, right HF).
• Biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
• Clinically relevant hepatic encephalopathy (Grade 2 or more) at screening or Day -1.
• Current functioning organ transplant or anticipated to receive organ transplant within 2 months of screening or Day -1.
• Has required new medication for hepatic encephalopathy within the 3 months prior to Day -1.
• Use of concurrent medication which affects creatinine clearance (eg, cephalosporin antibiotics, ascorbic acid, trimethoprim, cimetidine, or quinine) within 7 days of Day -1.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (3)

Research Site

Hialeah, Florida, 33014, United States

Location

Research Site

Orlando, Florida, 32809, United States

Location

Research Site

San Antonio, Texas, 78215, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Up to three cohorts (two hepatic impairment cohorts and controls with normal hepatic function) will be enrolled into this study. All subjects will receive the study intervention: * Cohort 1 will enroll 8 participants with moderate hepatic impairment * Cohort 2 will enroll 8-16 healthy participants matched by sex, age, and BMI * Cohort 3 (optional) will enroll 8 participants with mild hepatic impairment

Study Record Dates

• First Submitted: August 7, 2024
• First Posted: August 29, 2024
• Study Start: August 8, 2024
• Primary Completion: November 8, 2024
• Study Completion: November 8, 2024
• Last Updated: February 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

US (3)