Clinical trial NCT05751759: Pharmacokinetics of Mitiperstat in Participants With Hepatic Impairment
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Hepatic impairment
Liver disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-03-02
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Day 1 to Day 15
measure: Area under the concentration-time curve from time zero to infinity (AUCinf)
timeFrame: Day 1 to Day 15
measure: Area under the concentration-time curve from time zero to last time of quantifiable concentration (AUClast)
timeFrame: Day 1 to Day 15
measure: Apparent terminal elimination half-life (t½λz)
timeFrame: Day 1 to Day 15
measure: Time to Cmax (tmax)
timeFrame: Day 1 to Day 15
measure: Apparent Clearance (CL/F)
timeFrame: Day 1 to Day 15
measure: Volume of distribution (apparent) following extravascular administration [based on terminal phase] (Vz/F)
timeFrame: Day 1 to Day 15
measure: Cumulative amount of unchanged drug excreted into urine (Ae[0-24])
timeFrame: Day 1 to Day 15
measure: Renal clearance of drug from plasma (CLR)
timeFrame: Day 1 to Day 15
measure: Non-renal clearance of drug from plasma (CLNR)
timeFrame: Day 1 to Day 15
measure: Percentage of dose excreted unchanged in urine from time 0 to time 24 (fe[0-24)
timeFrame: Day 1 to Day 15
Secondary outcomes:
measure: Adverse Events (AEs), and Serious Adverse Events (SAEs)
timeFrame: From time of dose to the final follow-up visit (Day 21 [± 4 days])
Other outcomes:
Locations:
city: Rialto
country: United States
facility: Research Site
state: California
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Canton
country: United States
facility: Research Site
state: Ohio
city: San Antonio
country: United States
facility: Research Site
state: Texas
Study officials:
References: