Pharmacokinetics of Mitiperstat in Participants With Hepatic Impairment

Hepatic Impairment Clinical Trial

Official title:

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 Mitiperstat

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05751759
• Other study ID #: D6581C00002
• Status: Recruiting
• Phase: Phase 1
• Start date: March 20, 2023
• Est. completion date: August 20, 2024

Study information

• Verified date: May 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

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

Description:

This is a Phase I, single dose, non-randomised, open-label, parallel group study to examine the PK, safety, and tolerability of mitiperstat in participants with hepatic impairment and participants with normal hepatic function.

Participants will be assigned to one of the following cohorts as per Child-Pugh classification:

• Cohort 1: Eight participants with Mild hepatic impairment (Child-Pugh A)

• Cohort 2: Eight participants with Moderate hepatic impairment (Child-Pugh B)

• Cohort 3: Six to eight participants with Severe hepatic impairment (Child-Pugh C)

• Cohort 4: Eight to twelve participants with Normal hepatic function

A final safety follow-up visit on Day 21 will be there after all procedures are completed on Day 15.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: August 20, 2024
• Est. primary completion date: August 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• 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.

1. Criterion not applicable to this CSP version.

2. 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.

Exclusion Criteria:

• 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.

• Oesophageal variceal bleeding in prior 3 months.

• Platelet count < 50 × 109/L and/or neutrophil count < 1.2 × 109/L and/or haemoglobin < 85 g/L.

• Post liver transplantation.

• History of acute or chronic pancreatitis, or pancreatic amylase or lipase greater than twice the ULN at screening.

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Mitiperstat
Participants receive mitiperstat orally.

Locations

Country	Name	City	State
United States	Research Site	Canton	Ohio
United States	Research Site	Hialeah	Florida
United States	Research Site	Orlando	Florida
United States	Research Site	Rialto	California
United States	Research Site	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Apparent terminal elimination half-life (t½?z)	The t½?z 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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Adverse Events (AEs), and Serious Adverse Events (SAEs)	The safety, and tolerability of a single dose of mitiperstat in participants with hepatic impairment and controls with normal hepatic function will be assessed.	From time of dose to the final follow-up visit (Day 21 [± 4 days])