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

A Phase I, Single-Dose, Non-Randomised, Open-label, Parallel Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD0780

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: AZD0780

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 AZD0780 dose 1 administered orally to male and female participants (females of non-childbearing potential) with moderate hepatic impairment and mild hepatic impairment (optional) compared with male and female participants (females of non-childbearing potential) with normal hepatic function.

Participants will be enrolled within the following groups based on their Child Pugh classification score as determined at screening:

• Group 1: Participants with moderate hepatic impairment (Child Pugh Class B, score of 7 to 9).
• Group 2: Participants with normal hepatic function demographically matched by sex, age, and body mass index (BMI) to the impaired participants.
• Group 3 (optional): Participants with mild hepatic impairment (Child Pugh Class A, score of 5 or 6).

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Hialeah, Florida, United States, 33014
      • Research Site
    • Orlando, Florida, United States, 32809
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78215
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

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.
• Current or previous treatment with drugs for reduction or inhibition of PCSK9 (eg, evolocumab, alirocumab, or inclisiran).
• Use of moderate/strong inhibitors or inducers of CYP3A4/5.
• Unable to refrain from potassium binders, phosphate binders (eg, aluminium hydroxide and calcium carbonate), cholestyramine/colestipol, and ranitidine/nizatidine within 10 hours before and 10 hours after study intervention.
• Receiving or has received within 14 days of screening, medication that contains a black box warning for significant QT prolongation. A list of prohibited medications can be found in the protocol.
• Unable to refrain from lactulose within 10 hours before and 10 hours after study intervention.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Subjects with Moderate Impairment will receive a single oral dose of AZD0780 under fasted conditions.	Drug: AZD0780; Dose 1; Other Names: Dose 1
Experimental: Group 2; Healthy participants will receive a single oral dose of AZD0780 under fasted conditions.	Drug: AZD0780; Dose 1; Other Names: Dose 1
Experimental: Group 3 (optional); Subjects with Mild Impairment will receive a single oral dose of AZD0780 under fasted conditions.	Drug: AZD0780; Dose 1; Other Names: Dose 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	To assess the safety and tolerability of a single oral dose of AZD0780 in participants with moderate and mild (optional) hepatic impairment and those with normal hepatic function	Day 1 to Day 11
Number of participants with abnormal Vital signs, abnormal ECGs, and abnormal physical examination findings	To assess the safety and tolerability of a single oral dose of AZD0780 in participants with moderate and mild (optional) hepatic impairment and those with normal hepatic function	Day 1 to Day 11
Number of participants with abnormal laboratory tests results	To assess the safety and tolerability of a single oral dose of AZD0780 in participants with moderate and mild (optional) hepatic impairment and those with normal hepatic function	Day 1 to Day 11
Tmax	Time to reach maximum observed plasma concentration	Day 1 to Day 11
PK parameters (t1/2λz)	Terminal elimination half-life	Day 1 to Day 11
PK parameters (CL/F)	Apparent plasma clearance	Day 1 to Day 11
PK parameters (Vz/F)	Apparent volume of distribution during the terminal phase	Day 1 to Day 11
PK parameters (AUC0-96)	Area under the plasma concentration-time curve from time zero to 96 hours	Day 1 to Day 5
PK parameters (CLR)	Renal clearance of drug from plasma	Day 1 to Day 11
PK parameters (Ae)	Amount excreted in urine	Day 1 to Day 11
PK parameters (fe)	Fraction of dose excreted in urine	Day 1 to Day 11

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multi-omics Analysis	To explore how multi-omics variations, including genetics, may affect clinical parameters, risk, and prognosis of diseases and the response to medications. Exploratory endpoints are related to the data generated from multi-omics analysis, including genetics, which may be part or all of the participant's genetic information.	Day 1

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2024
• Primary Completion (Actual): November 8, 2024
• Study Completion (Actual): November 8, 2024

Study Registration Dates

• First Submitted: August 7, 2024
• First Submitted That Met QC Criteria: August 27, 2024
• First Posted (Actual): August 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 7, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Healthy participants; Hepatic Impairment; AZD0780
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: D7960C00010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing 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
• IPD Sharing 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

Drug and device information, study documents

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