Hepatic ImpairmentPhase 1NCT05751759
Pharmacokinetics of Mitiperstat in Participants With Hepatic Impairment
A Phase 1 study testing Mitiperstat in people with Hepatic Impairment, run by AstraZeneca at 5 sites in United States.
Trial summary
This study will assess the effect of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of mitiperstat. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- Mitiperstat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 5 sitesUnited States
- Study dates
- 20 Mar 2023to 21 Nov 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Research Site
Canton, Ohio, 44718
Research Site
Hialeah, Florida, 33016
Research Site
Orlando, Florida, 32808
Research Site
Rialto, California, 92377
Research Site
San Antonio, Texas, 78215
About this study
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
This study will assess the effect of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of mitiperstat.
Read the 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.
- Conditions
- Hepatic Impairment
- Being tested
- Mitiperstat
- Keywords
- Hepatic impairment, Liver disease
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MitiperstatDrug
Also called AZD4831
Participants receive mitiperstat orally.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 8 participants with mild hepatic impairment (Child-Pugh A) will be given Dose A of mitiperstat. Receives: Drug: Mitiperstat |
| Cohort 2 | Experimental | 8 participants with moderate hepatic impairment (Child-Pugh B) will be given Dose A of mitiperstat. Receives: Drug: Mitiperstat |
| Cohort 3 | Experimental | 6-8 participants with severe hepatic impairment (Child-Pugh C) will be given Dose A of mitiperstat. Receives: Drug: Mitiperstat |
| Cohort 4 | Experimental | 8-12 participants with normal hepatic function will be given Dose A of mitiperstat. Receives: Drug: Mitiperstat |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 to Day 15
Secondary outcomes (1)
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.
Measured: From time of dose to the final follow-up visit (Day 21 [± 4 days])
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2023
- Study start20 Mar 2023
- Primary completion21 Nov 2024
- Study completion21 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05751759
- Sponsor's protocol ID
- D6581C00002
- Status last verified
- Dec 2024
- First submitted
- 21 Feb 2023
- Last updated
- 5 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual participant-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.
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05751759
- Acronym / sponsor ID
- D6581C00002
- Conditions
- Hepatic Impairment
- Keywords
- Hepatic impairment, Liver disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 20 Mar 2023 (actual)
- Primary completion
- 21 Nov 2024 (actual)
- Study completion
- 21 Nov 2024 (actual)
- First posted
- 2 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Mitiperstat8 participants with mild hepatic impairment (Child-Pugh A) will be given Dose A of mitiperstat. |
| Cohort 2 | Experimental | Drug: Mitiperstat8 participants with moderate hepatic impairment (Child-Pugh B) will be given Dose A of mitiperstat. |
| Cohort 3 | Experimental | Drug: Mitiperstat6-8 participants with severe hepatic impairment (Child-Pugh C) will be given Dose A of mitiperstat. |
| Cohort 4 | Experimental | Drug: Mitiperstat8-12 participants with normal hepatic function will be given Dose A of mitiperstat. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
- Capable of giving signed informed consent.
Key exclusion criteria (19 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MitiperstatAlso: AZD4831Participants receive mitiperstat orally. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
Primary outcome
Maximum observed plasma concentration (Cmax)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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])
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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.
1 secondary outcome
Adverse Events (AEs), and Serious Adverse Events (SAEs)
Time frame: From time of dose to the final follow-up visit (Day 21 [± 4 days])
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2024.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual participant-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mitiperstat in people with Hepatic Impairment, run by AstraZeneca at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum observed plasma concentration (Cmax) (time frame: Day 1 to Day 15). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2024.