Liver CirrhosisPhase 1NCT06715670
A Study to Investigate the Blood Concentrations of 4 Different Oral Doses of Zibotentan in Healthy Non-Asian and Japanese Participants
A Phase 1 study testing Zibotentan in people with Liver Cirrhosis, run by AstraZeneca at 1 site in United States.
Trial summary
This study aim to assess the Pharmacokinetics of Zibotentan in Healthy Non-Asian and Japanese Participants. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Liver Cirrhosis
- What is being tested?
- Zibotentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Dec 2024to 28 Feb 2025
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and female (non-childbearing potential) with suitable veins for cannulation or repeated venipuncture.
- All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
- Females of non-childbearing potential must be confirmed at the Screening Visit.
- Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods.
- Body mass index (BMI) between 18 and 32 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive at Screening.
- Japanese participant must have Japanese parents and grandparents, were born in Japan, and not have lived outside Japan for over 10 years.
- Participant is considered non-Asian if their parents and all grandparents are ethnically non-Asian.
Who cannot join
- History of any clinically important disease or disorder which may either put the participant at risk because of participation in the study or influence the results or the participant's ability to participate in the study.
- History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
- Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis, laboratory values and vital signs at the Screening Visit.
- Any positive result on Screening for serum HBsAg (Hepatitis B surface antigen), HBcAb (Hepatitis B core antibody) or HIV (Human immunodeficiency virus).
- Clinically significant abnormal findings in vital signs after 10 minutes of supine rest.
Show all 21Show fewer
- Clinically important abnormalities in rhythm, conduction, or morphology of the resting electrocardiography (ECG) and prolonged QTcF > 450 ms, family history of long QT syndrome, or early cardiac death.
- Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
- Positive screen for drugs of abuse or alcohol at Screening or first admission.
- History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
- Excessive intake of caffeine-containing drinks or food.
- Use of any prescribed or nonprescribed medication, including antacids, analgesics, herbal remedies, mega dose vitamins, and minerals within 2 weeks before the first administration of the study intervention.
- Plasma donation within one month of the Screening Visit or any blood donation/blood loss > 500 mL during the 3 months before the Screening Visit.
- Receipt of another new chemical entity within 30 days or 5 half-lives (whichever is longest) of the first administration of the study intervention.
- Previous receipt of zibotentan within 28 days before Day 1 dosing in the Clinical Unit.
- Treatment with strong or moderate Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 28 days or 5 half-lives (whichever is longest) or weak CYP3A4 inhibitors or inducers within 3 days or 3 half-lives (whichever is longest) before dosing.
- Involvement in the planning and/or conduct of the study.
- Ongoing or recent minor medical complaints that may interfere with the interpretation of study data or compliance with study procedures.
- Being vegan or having medical dietary restrictions.
- Inability to communicate reliably with the Principal Investigator or designee.
- Being a vulnerable participant, such as those kept in detention, under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Randomized, Open-label, Single-dose, Four-period, Four-treatment, Cross-over Study to Assess the Pharmacokinetics of Zibotentan in Healthy Non-Asian and Japanese Participants
This study aim to assess the Pharmacokinetics of Zibotentan in Healthy Non-Asian and Japanese Participants.
Read the detailed description
This study will be Phase I, randomized, open-label, single-dose, 4-period, 4-treatment, cross-over study, performed at a single study center.
The study will comprise: Screening Period of maximum 28 days; Four Treatment Periods, separated by 3 washout periods; Final Follow-up Visit within 5 to 7 days after the last study intervention administration. The washout periods will last at least 3 days, resulting in a total dosing-free time of at least 6 full days between each of the 4 treatments. Participant will receive the first dose is on Day 1, then the next dose will be on Day 8 at the earliest.
Each participant will receive 4 different single doses (Dose 1, 2, 3 and 4) of zibotentan, at all 4 studied dose levels in one of the following treatment sequences: ABCD, BDAC, CADB, DCBA.
Each participant will be involved in the study for approximately 9 weeks, depending upon the duration of the washout periods.
- Conditions
- Liver Cirrhosis
- Being tested
- Zibotentan
- Keywords
- Chronic kidney disease, Treatment sequence, Pharmacokinetics, Washout periods
- Medical subject headings
- Liver Cirrhosis, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZibotentanDrug
Participant will receive 4 different single doses of zibotentan on Day 1 of each treatment period orally.
| Study group | Role | What they receive |
|---|---|---|
| Treatment sequence ABCD: Zibotentan | Experimental | Participants will receive single dose of Zibotentan in 4 occassions with first Treatment A, followed by Treatment B, Treatment C and then Treatment D with each dose separated by 3 washout periods. Receives: Drug: Zibotentan |
| Treatment sequence BDAC: Zibotentan | Experimental | Participants will receive single dose of Zibotentan in 4 occassions with first Treatment B, followed by Treatment D, Treatment A and then Treatment C with each dose separated by 3 washout periods Receives: Drug: Zibotentan |
| Treatment sequence CADB: Zibotentan | Experimental | Participants will receive single dose of Zibotentan in 4 occassions with first Treatment C, followed by Treatment A, Treatment D and then Treatment B with each dose separated by 3 washout periods. Receives: Drug: Zibotentan |
| Treatment sequence DCBA: Zibotentan | Experimental | Participants will receive single dose of Zibotentan in 4 occassions with first Treatment D, followed by Treatment C, Treatment B and then Treatment A with each dose separated by 3 washout periods. Receives: Drug: Zibotentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under concentration-time curve from time 0 to infinity (AUCinf)
To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants.
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants.
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Maximum observed drug concentration (Cmax)
To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Secondary outcomes (12)
Number of participants with adverse events (AEs) receiving single dose
To assess the safety and tolerability of receiving single dose of orally administered zibotentan.
Measured: From Screening (28 days) to follow-up Visit 5 to 7 days post-final dose (approximately 9 weeks)
Concentration at 24 hours post dose (C24)
To further characterize zibotentan PK in plasma.
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Partial area under the concentration time curve from time 0 to 24 hours post-dose (AUC(0-24))
To further characterize zibotentan PK in plasma.
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Time to reach maximum observed concentration (tmax)
To further characterize zibotentan PK in plasma.
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Terminal elimination half-life (t1/2 λz)
To further characterize zibotentan PK in plasma.
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Mean residence time (MRTinf)
To further characterize zibotentan PK in plasma.
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Terminal rate constant (λz)
To further characterize zibotentan PK in plasma.
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Apparent total body clearance (CL/F)
To further characterize zibotentan PK in plasma.
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Apparent volume of distribution based on the terminal phase (Vz/F)
To further characterize zibotentan PK in plasma.
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Individual and cumulative amount of unchanged drug excreted into urine (Ae) (by time point and cumulative)
To further characterize zibotentan PK in urine.
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 (fe) (by time point and cumulative)
To further characterize zibotentan PK in urine.
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Renal clearance (CLR)
To further characterize zibotentan PK in urine.
Measured: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2024
- Study start5 Dec 2024
- Primary completion28 Feb 2025
- Study completion28 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CirrhosisStudies 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
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06715670
- Sponsor's protocol ID
- D4326C00010
- Status last verified
- Dec 2025
- First submitted
- 29 Nov 2024
- Last updated
- 4 Dec 2025
- 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 patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. 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 approved.
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomized, Open-label, Single-dose, Four-period, Four-treatment, Cross-over Study to Assess the Pharmacokinetics of Zibotentan in Healthy Non-Asian and Japanese Participants
- ClinicalTrials.gov ID
- NCT06715670
- Acronym / sponsor ID
- D4326C00010
- Conditions
- Liver Cirrhosis
- Keywords
- Chronic kidney disease, Treatment sequence, Pharmacokinetics, Washout periods
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 5 Dec 2024 (actual)
- Primary completion
- 28 Feb 2025 (actual)
- Study completion
- 28 Feb 2025 (actual)
- First posted
- 4 Dec 2024 (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 aim to assess the Pharmacokinetics of Zibotentan in Healthy Non-Asian and Japanese Participants.
Detailed description
This study will be Phase I, randomized, open-label, single-dose, 4-period, 4-treatment, cross-over study, performed at a single study center.
The study will comprise: Screening Period of maximum 28 days; Four Treatment Periods, separated by 3 washout periods; Final Follow-up Visit within 5 to 7 days after the last study intervention administration. The washout periods will last at least 3 days, resulting in a total dosing-free time of at least 6 full days between each of the 4 treatments. Participant will receive the first dose is on Day 1, then the next dose will be on Day 8 at the earliest.
Each participant will receive 4 different single doses (Dose 1, 2, 3 and 4) of zibotentan, at all 4 studied dose levels in one of the following treatment sequences: ABCD, BDAC, CADB, DCBA.
Each participant will be involved in the study for approximately 9 weeks, depending upon the duration of the washout periods.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment sequence ABCD: Zibotentan | Experimental | Drug: ZibotentanParticipants will receive single dose of Zibotentan in 4 occassions with first Treatment A, followed by Treatment B, Treatment C and then Treatment D with each dose separated by 3 washout periods. |
| Treatment sequence BDAC: Zibotentan | Experimental | Drug: ZibotentanParticipants will receive single dose of Zibotentan in 4 occassions with first Treatment B, followed by Treatment D, Treatment A and then Treatment C with each dose separated by 3 washout periods |
| Treatment sequence CADB: Zibotentan | Experimental | Drug: ZibotentanParticipants will receive single dose of Zibotentan in 4 occassions with first Treatment C, followed by Treatment A, Treatment D and then Treatment B with each dose separated by 3 washout periods. |
| Treatment sequence DCBA: Zibotentan | Experimental | Drug: ZibotentanParticipants will receive single dose of Zibotentan in 4 occassions with first Treatment D, followed by Treatment C, Treatment B and then Treatment A with each dose separated by 3 washout periods. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and female (non-childbearing potential) with suitable veins for cannulation or repeated venipuncture.
- All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
- Females of non-childbearing potential must be confirmed at the Screening Visit.
- Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods.
Key exclusion criteria (21 listed)
- History of any clinically important disease or disorder which may either put the participant at risk because of participation in the study or influence the results or the participant's ability to participate in the study.
- History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
- Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis, laboratory values and vital signs at the Screening Visit.
- Any positive result on Screening for serum HBsAg (Hepatitis B surface antigen), HBcAb (Hepatitis B core antibody) or HIV (Human immunodeficiency virus).
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 |
|---|---|---|
| ZibotentanParticipant will receive 4 different single doses of zibotentan on Day 1 of each treatment period orally. | Drug | Treatment sequence ABCD: Zibotentan, Treatment sequence BDAC: Zibotentan, Treatment sequence CADB: Zibotentan, Treatment sequence DCBA: Zibotentan |
Primary outcome
Area under concentration-time curve from time 0 to infinity (AUCinf)
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants.
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants.
Maximum observed drug concentration (Cmax)
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants
12 secondary outcomes
Number of participants with adverse events (AEs) receiving single dose
Time frame: From Screening (28 days) to follow-up Visit 5 to 7 days post-final dose (approximately 9 weeks)
Concentration at 24 hours post dose (C24)
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Partial area under the concentration time curve from time 0 to 24 hours post-dose (AUC(0-24))
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Time to reach maximum observed concentration (tmax)
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Terminal elimination half-life (t1/2 λz)
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Mean residence time (MRTinf)
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Terminal rate constant (λz)
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Apparent total body clearance (CL/F)
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Apparent volume of distribution based on the terminal phase (Vz/F)
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Individual and cumulative amount of unchanged drug excreted into urine (Ae) (by time point and cumulative)
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 (fe) (by time point and cumulative)
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Renal clearance (CLR)
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 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 4 Dec 2025.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. 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 approved.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Zibotentan in people with Liver Cirrhosis, run by AstraZeneca at 1 site 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 8 inclusion and 21 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 4 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Area under concentration-time curve from time 0 to infinity (AUCinf) (time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)). The study lists 3 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 4 Dec 2025.