Pharmacokinetics of Mitiperstat in Participants With Hepatic Impairment

NCT05751759 | Completed Phase 1 FDA Drug

• 1 other identifier: D6581C00002
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 5

Brief Summary

This study will assess the effect of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of mitiperstat.

Conditions

Hepatic Impairment

Keywords

Hepatic impairment; Liver disease

Outcome Measures

Primary Outcomes (11)

• Maximum observed plasma concentration (Cmax)

  The Cmax of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated and compared.

  Day 1 to Day 15

• Area under the concentration-time curve from time zero to infinity (AUCinf)

  The AUCinf of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated and compared.

  Day 1 to Day 15

• Area under the concentration-time curve from time zero to last time of quantifiable concentration (AUClast)

  The AUClast of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated and compared.

  Day 1 to Day 15

• Apparent terminal elimination half-life (t½λz)

  The t½λz of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.

  Day 1 to Day 15

• Time to Cmax (tmax)

  The tmax of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.

  Day 1 to Day 15

• Apparent Clearance (CL/F)

  The CL/F of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.

  Day 1 to Day 15

• Volume of distribution (apparent) following extravascular administration [based on terminal phase] (Vz/F)

  The Vz/F of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.

  Day 1 to Day 15

• Cumulative amount of unchanged drug excreted into urine (Ae[0-24])

  The Ae(0-24) of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.

  Day 1 to Day 15

• Renal clearance of drug from plasma (CLR)

  The CLR of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.

  Day 1 to Day 15

• Non-renal clearance of drug from plasma (CLNR)

  The CLNR of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.

  Day 1 to Day 15

• Percentage of dose excreted unchanged in urine from time 0 to time 24 (fe[0-24)

  The fe(0-24) of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.

  Day 1 to Day 15

Secondary Outcomes (1)

• Adverse Events (AEs), and Serious Adverse Events (SAEs)

  From time of dose to the final follow-up visit (Day 21 [± 4 days])

Study Arms (4)

Cohort 1

EXPERIMENTAL

8 participants with mild hepatic impairment (Child-Pugh A) will be given Dose A of mitiperstat.

Drug: Mitiperstat

Cohort 2

EXPERIMENTAL

8 participants with moderate hepatic impairment (Child-Pugh B) will be given Dose A of mitiperstat.

Drug: Mitiperstat

Cohort 3

EXPERIMENTAL

6-8 participants with severe hepatic impairment (Child-Pugh C) will be given Dose A of mitiperstat.

Drug: Mitiperstat

Cohort 4

EXPERIMENTAL

8-12 participants with normal hepatic function will be given Dose A of mitiperstat.

Drug: Mitiperstat

Interventions

Mitiperstat DRUG

Participants receive mitiperstat orally.

Also known as: AZD4831

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be ≥ 18 to ≤ 85 years (inclusive), at the time of signing the informed consent.
• Weight ≥ 50kg and BMI ≥ 18 kg/m2 up to \< 42 kg/m2.
• Male and/or females.
• Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Criterion not applicable to this CSP version.
• Female participants:
• Female participants must not be lactating.
• Female participants of childbearing potential who are sexually active with a non-sterilised male partner must agree to use an acceptable method of birth control, from enrolment throughout the study and until at least 4 weeks after the last dose of study intervention.
• Capable of giving signed informed consent.
• Participants with hepatic impairment only:
• Supporting documents confirming that the participant has liver cirrhosis with hepatic impairment must be available.
• Diagnosis of chronic and stable hepatic impairment.

You may not qualify if:

• Any positive result on screening for serum or plasma hepatitis B surface antigen, hepatitis C antibody, and HIV.
• History of substance dependence or a positive screen for drugs of abuse, likely to impact participant safety or compliance with study procedures.
• History of alcohol abuse or excessive intake of alcohol in the last 12 months.
• Abnormal vital signs, after 10 minutes supine rest at screening or Day -1.
• Any clinically important abnormalities in rhythm, conduction or morphology of the resting 12-lead ECG at screening or Day -1:
• Vulnerable participants.
• For female participants only: currently pregnant or breast-feeding.
• Participants with hepatic impairment only
• Participants with previous transjugular intrahepatic portosystemic shunt (TIPS).
• Severe ascites defined as ascites requiring paracentesis and albumin at 4-week intervals or less.
• 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.
• Any evidence of additional severe or uncontrolled systemic disease or laboratory finding that makes it unsafe for the participant to participate in the study.
• Change in dose regimen of medically-required medication within the last 2 weeks before pre-study examination.
• Biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
• Clinically relevant hepatic encephalopathy.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (5)

Research Site

Rialto, California, 92377, United States

Location

Research Site

Hialeah, Florida, 33016, United States

Location

Research Site

Orlando, Florida, 32808, United States

Location

Research Site

Canton, Ohio, 44718, United States

Location

Research Site

San Antonio, Texas, 78215, United States

Location

MeSH Terms

Conditions

Liver Diseases

Interventions

AZD4831

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Design

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

Study Record Dates

• First Submitted: February 21, 2023
• First Posted: March 2, 2023
• Study Start: March 20, 2023
• Primary Completion: November 21, 2024
• Study Completion: November 21, 2024
• Last Updated: December 5, 2024

Record last verified: 2024-12

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 (5)