Pharmacokinetics of Mitiperstat in Participants With Hepatic Impairment
Study Details
Study Description
Brief Summary
This study will assess the effect of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of mitiperstat.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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:
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Cohort 1: Eight participants with Mild hepatic impairment (Child-Pugh A)
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Cohort 2: Eight participants with Moderate hepatic impairment (Child-Pugh B)
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Cohort 3: Eight participants with Severe hepatic impairment (Child-Pugh C)
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 8 participants with mild hepatic impairment (Child-Pugh A) will be given Dose A of mitiperstat. |
Drug: Mitiperstat
Participants receive mitiperstat orally.
Other Names:
|
| Experimental: Cohort 2 8 participants with moderate hepatic impairment (Child-Pugh B) will be given Dose A of mitiperstat. |
Drug: Mitiperstat
Participants receive mitiperstat orally.
Other Names:
|
| Experimental: Cohort 3 8 participants with severe hepatic impairment (Child-Pugh C) will be given Dose A of mitiperstat. |
Drug: Mitiperstat
Participants receive mitiperstat orally.
Other Names:
|
| Experimental: Cohort 4 8-12 participants with normal hepatic function will be given Dose A of mitiperstat. |
Drug: Mitiperstat
Participants receive mitiperstat orally.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum observed plasma concentration (Cmax) [Day 1 to Day 15]
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.
- Area under the concentration-time curve from time zero to infinity (AUCinf) [Day 1 to Day 15]
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.
- Area under the concentration-time curve from time zero to last time of quantifiable concentration (AUClast) [Day 1 to Day 15]
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.
- Apparent terminal elimination half-life (t½λz) [Day 1 to Day 15]
The t½λz of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
- Time to Cmax (tmax) [Day 1 to Day 15]
The tmax of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
- Apparent Clearance (CL/F) [Day 1 to Day 15]
The CL/F of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
- Volume of distribution (apparent) following extravascular administration [based on terminal phase] (Vz/F) [Day 1 to Day 15]
The Vz/F of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
- Cumulative amount of unchanged drug excreted into urine (Ae[0-24]) [Day 1 to Day 15]
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.
- Renal clearance of drug from plasma (CLR) [Day 1 to Day 15]
The CLR of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
- Non-renal clearance of drug from plasma (CLNR) [Day 1 to Day 15]
The CLNR of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
- Percentage of dose excreted unchanged in urine from time 0 to time 24 (fe[0-24) [Day 1 to Day 15]
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.
Secondary Outcome Measures
- Adverse Events (AEs), and Serious Adverse Events (SAEs) [From time of dose to the final follow-up visit (Day 21 [± 4 days])]
The safety, and tolerability of a single dose of mitiperstat in participants with hepatic impairment and controls with normal hepatic function will be assessed.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participant must be ≥ 18 to ≤ 85 years (inclusive), at the time of signing the informed consent.
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Weight ≥ 50kg and BMI ≥ 18 kg/m2 up to < 40 kg/m2.
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Male or females of non-childbearing potential.
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Contraceptive use by males should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Male participants:
Use of a condom plus an additional contraceptive method until the end of relevant systemic exposure in the exposed male plus 90 days.
- Female participants:
Females not of child-bearing potential are defined as females who are either permanently sterilised, or who are postmenopausal.
- Capable of giving signed informed consent.
Participants with hepatic impairment only:
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Supporting documents confirming that the participant has liver cirrhosis with hepatic impairment must be available.
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Diagnosis of chronic and stable hepatic impairment.
Exclusion Criteria:
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Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and HIV.
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History of substance dependence or a positive screen for drugs of abuse, likely to impact participant safety or compliance with study procedures.
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History of alcohol abuse or excessive intake of alcohol in the last 12 months.
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Abnormal vital signs, after 10 minutes supine rest at screening or Day -1.
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Any clinically important abnormalities in rhythm, conduction or morphology of the resting 12-lead ECG at screening or Day -1:
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Vulnerable participants.
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For female participants only: currently pregnant or breast-feeding.
Participants with hepatic impairment only
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Participants with previous transjugular intrahepatic portosystemic shunt (TIPS).
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Severe ascites defined as ascites requiring paracentesis and albumin at 4-week intervals or less.
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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.
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Any evidence of additional severe or uncontrolled systemic disease or laboratory finding that makes it unsafe for the participant to participate in the study.
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Change in dose regimen of medically-required medication within the last 2 weeks before pre-study examination.
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Biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
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Clinically relevant hepatic encephalopathy.
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Oesophageal variceal bleeding in prior 3 months.
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Platelet count < 50 × 109/L and/or neutrophil count < 1.2 × 109/L and/or haemoglobin < 85 g/L.
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Post liver transplantation.
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History of acute or chronic pancreatitis, or pancreatic amylase or lipase greater than twice the ULN at screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | San Antonio | Texas | United States | 78215 |
Sponsors and Collaborators
- AstraZeneca
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D6581C00002