Chronic Kidney DiseasePhase 1NCT04991571
Study to Collect Samples for MIST Analysis of Zibotentan and Bioavailability of Zibotentan and Dapagliflozin in Heatlhy Participants
A Phase 1 study testing Zibotentan (Treatment A), Dapagliflozin (Treatment A) and Zibotentan/Dapagliflozin - Formulation 1 (Treatment B) in people with Chronic Kidney Disease, run by AstraZeneca at 1 site in United States.
Trial summary
The study will have 2 independent parts: Part 1 of the study is intended to collect samples for Metabolites in Safety Testing (MIST) analysis after administration of multiple doses of zibotentan. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Kidney Disease
- What is being tested?
- Zibotentan (Treatment A), Dapagliflozin (Treatment A) and Zibotentan/Dapagliflozin - Formulation 1 (Treatment B)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jul 2021to 22 Oct 2021
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- For inclusion in the study participants should fulfil the following criteria:
- Participants with suitable veins for cannulation or repeated venipuncture.
- Females must have a negative pregnancy test at the Screening Visit and within 24 hours prior to dosing, must not be lactating and must be of non- childbearing potential
- Male participant must adhere to the contraception methods.
- Have a BMI between 18 and 29.9 kg/m^2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- Provision of signed and dated, written informed consent prior to any study specific procedures.
Who cannot join
- Participants will not enter the study if any of the following exclusion criteria are fulfilled:
- History or presence of gastrointestinal, hepatic or renal disease or any important disease or disorder.
- Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study intervention.
- Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis.
- Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and Human immunodeficiency virus antibody.
- Abnormal vital signs. 6 History of drug abuse or alcohol abuse.
- 7. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
- 8. Participants who are vegans or have medical dietary restrictions. 9. Participants tested positive for COVID-19 at the time of randomisation or have been previously hospitalised with COVID-19 infection.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-label Study With Two Independent Parts: Collecting Samples for Metabolites in Safety Testing Analysis of Zibotentan After Repeated Administration (Part 1); and a Randomised, Cross-over, Three Period, Three-treatment, Single Dose Study to Assess the Relative Bioavailability of Different Formulations of Zibotentan and Dapagliflozin (Part 2) in Healthy Adult Participants
The study will have 2 independent parts:
Part 1 of the study is intended to collect samples for Metabolites in Safety Testing (MIST) analysis after administration of multiple doses of zibotentan.
Part 2 of the study is designed to evaluate the relative bioavailability of zibotentan and dapagliflozin after dosing with two different fixed-dose combination (FDC) formulations and dosing with separate formulations of zibotentan and dapagliflozin.
Read the detailed description
Part 1 will be an open-label, non-randomised, single treatment period. A single treatment period during which participants will be resident at the study centre from 2 days before dosing (Day -2) until the morning of Day 6.
Part 2 will be an open-label, randomised, 3-period, 3-treatment, cross-over single dose study. Participants will be randomised to one of 3 treatment sequences and will receive 3 single-dose study interventions. Participants will be resident at the study centre from 2 days before dosing (Day -2) until Day 3 of the last treatment sequence.
Participants who were enrolled in Part 1 may not be enrolled in Part 2.
- Conditions
- Chronic Kidney Disease
- Being tested
- Zibotentan (Treatment A), Dapagliflozin (Treatment A), Zibotentan/Dapagliflozin - Formulation 1 (Treatment B), Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zibotentan (Treatment A)Drug
Zibotentan capsule will be administered orally as multiple doses in Part 1 and as single dose in Part 2.
Dapagliflozin (Treatment A)Drug
Dapagliflozin tablet will be administered orally as single dose in Part 2.
Zibotentan/Dapagliflozin - Formulation 1 (Treatment B)Drug
Zibotentan/Dapagliflozin tablet will be administered orally as single dose in Part 2.
Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)Drug
Zibotentan/Dapagliflozin tablet will be administered orally as single dose in Part 2.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | Participants will be administered with zibotentan once daily for 5 days. Receives: Drug: Zibotentan (Treatment A) |
| Part 2: Treatment Sequence ABC | Experimental | Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment A; Treatment B; Treatment C) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods. Receives: Drug: Zibotentan (Treatment A); Drug: Dapagliflozin (Treatment A); Drug: Zibotentan/Dapagliflozin - Formulation 1 (Treatment B); Drug: Zibotentan/Dapagliflozin - Formulation 2 (Treatment C) |
| Part 2: Treatment Sequence BCA | Experimental | Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment B; Treatment C; Treatment A) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods. Receives: Drug: Zibotentan (Treatment A); Drug: Dapagliflozin (Treatment A); Drug: Zibotentan/Dapagliflozin - Formulation 1 (Treatment B); Drug: Zibotentan/Dapagliflozin - Formulation 2 (Treatment C) |
| Part 2: Treatment Sequence CAB | Experimental | Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment C; Treatment A; Treatment B) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods. Receives: Drug: Zibotentan (Treatment A); Drug: Dapagliflozin (Treatment A); Drug: Zibotentan/Dapagliflozin - Formulation 1 (Treatment B); Drug: Zibotentan/Dapagliflozin - Formulation 2 (Treatment C) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Metabolites in Safety Testing sampling
Plasma sample will be collected to understand the PK profiling of zibotentan metabolites and to meet the regulatory requirements.
Measured: Day 1 through Day 6 (pre-dose, 30 min; 1, 2, 4, 6, 8, 12 and 24 hours post dose)
Part 2: Area under plasma concentration time curve from zero to infinity (AUCinf)
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Measured: Day 1 through Day 3 of each treatment period
Part 2: Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Measured: Day 1 through Day 3 of each treatment period
Part 2: Maximum observed plasma drug concentration (Cmax)
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Measured: Day 1 through Day 3 of each treatment period
Part 2: Observed concentration at 24 hours post-dose (C24)
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Measured: Day 1 through Day 3 of each treatment period
Secondary outcomes (6)
Part 2: Time to reach peak or maximum observed concentration (tmax)
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Measured: Day 1 through Day 3 of each treatment period
Part 2: Terminal rate constant (λz)
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Measured: Day 1 through Day 3 of each treatment period
Part 2: Half life associated with λz (t½λz)
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Measured: Day 1 through Day 3 of each treatment period
Part 2: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Measured: Day 1 through Day 3 of each treatment period
Part 2: Volume of distribution at steady state following extravascular administration (Vz/F)
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Measured: Day 1 through Day 3 of each treatment period
Part 1 and Part 2: Number of adverse events and serious adverse events
Safety and tolerability of zibotentan and dapagliflozin will be studied.
Measured: From Sceerning to Follow-up Visit approximately 40 days for Part 1 and 49 days for Part 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2021
- Study start29 Jul 2021
- Primary completion22 Oct 2021
- Study completion22 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseaseStudies 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
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04991571
- Sponsor's protocol ID
- D4325C00003
- Status last verified
- Nov 2021
- First submitted
- 28 Jul 2021
- Last updated
- 23 Nov 2021
- 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. All request 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 23 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label Study With Two Independent Parts: Collecting Samples for Metabolites in Safety Testing Analysis of Zibotentan After Repeated Administration (Part 1); and a Randomised, Cross-over, Three Period, Three-treatment, Single Dose Study to Assess the Relative Bioavailability of Different Formulations of Zibotentan and Dapagliflozin (Part 2) in Healthy Adult Participants
- ClinicalTrials.gov ID
- NCT04991571
- Acronym / sponsor ID
- D4325C00003
- Conditions
- Chronic Kidney Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 29 Jul 2021 (actual)
- Primary completion
- 22 Oct 2021 (actual)
- Study completion
- 22 Oct 2021 (actual)
- First posted
- 5 Aug 2021 (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.
The study will have 2 independent parts:
Part 1 of the study is intended to collect samples for Metabolites in Safety Testing (MIST) analysis after administration of multiple doses of zibotentan.
Part 2 of the study is designed to evaluate the relative bioavailability of zibotentan and dapagliflozin after dosing with two different fixed-dose combination (FDC) formulations and dosing with separate formulations of zibotentan and dapagliflozin.
Detailed description
Part 1 will be an open-label, non-randomised, single treatment period. A single treatment period during which participants will be resident at the study centre from 2 days before dosing (Day -2) until the morning of Day 6.
Part 2 will be an open-label, randomised, 3-period, 3-treatment, cross-over single dose study. Participants will be randomised to one of 3 treatment sequences and will receive 3 single-dose study interventions. Participants will be resident at the study centre from 2 days before dosing (Day -2) until Day 3 of the last treatment sequence.
Participants who were enrolled in Part 1 may not be enrolled in Part 2.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: Zibotentan (Treatment A)Participants will be administered with zibotentan once daily for 5 days. |
| Part 2: Treatment Sequence ABC | Experimental | Drug: Zibotentan (Treatment A), Drug: Dapagliflozin (Treatment A), Drug: Zibotentan/Dapagliflozin - Formulation 1 (Treatment B), Drug: Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment A; Treatment B; Treatment C) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods. |
| Part 2: Treatment Sequence BCA | Experimental | Drug: Zibotentan (Treatment A), Drug: Dapagliflozin (Treatment A), Drug: Zibotentan/Dapagliflozin - Formulation 1 (Treatment B), Drug: Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment B; Treatment C; Treatment A) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods. |
| Part 2: Treatment Sequence CAB | Experimental | Drug: Zibotentan (Treatment A), Drug: Dapagliflozin (Treatment A), Drug: Zibotentan/Dapagliflozin - Formulation 1 (Treatment B), Drug: Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment C; Treatment A; Treatment B) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Participants with suitable veins for cannulation or repeated venipuncture.
- Females must have a negative pregnancy test at the Screening Visit and within 24 hours prior to dosing, must not be lactating and must be of non- childbearing potential
- Male participant must adhere to the contraception methods.
- Have a BMI between 18 and 29.9 kg/m^2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- Provision of signed and dated, written informed consent prior to any study specific procedures.
Key exclusion criteria (8 listed)
- Participants will not enter the study if any of the following exclusion criteria are fulfilled:
- History or presence of gastrointestinal, hepatic or renal disease or any important disease or disorder.
- Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study intervention.
- Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis.
- Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and Human immunodeficiency virus antibody.
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 |
|---|---|---|
| Zibotentan (Treatment A)Zibotentan capsule will be administered orally as multiple doses in Part 1 and as single dose in Part 2. | Drug | Part 1, Part 2: Treatment Sequence ABC, Part 2: Treatment Sequence BCA, Part 2: Treatment Sequence CAB |
| Dapagliflozin (Treatment A)Dapagliflozin tablet will be administered orally as single dose in Part 2. | Drug | Part 2: Treatment Sequence ABC, Part 2: Treatment Sequence BCA, Part 2: Treatment Sequence CAB |
| Zibotentan/Dapagliflozin - Formulation 1 (Treatment B)Zibotentan/Dapagliflozin tablet will be administered orally as single dose in Part 2. | Drug | Part 2: Treatment Sequence ABC, Part 2: Treatment Sequence BCA, Part 2: Treatment Sequence CAB |
| Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)Zibotentan/Dapagliflozin tablet will be administered orally as single dose in Part 2. | Drug | Part 2: Treatment Sequence ABC, Part 2: Treatment Sequence BCA, Part 2: Treatment Sequence CAB |
Primary outcome
Part 1: Metabolites in Safety Testing sampling
Time frame: Day 1 through Day 6 (pre-dose, 30 min; 1, 2, 4, 6, 8, 12 and 24 hours post dose)
Plasma sample will be collected to understand the PK profiling of zibotentan metabolites and to meet the regulatory requirements.
Part 2: Area under plasma concentration time curve from zero to infinity (AUCinf)
Time frame: Day 1 through Day 3 of each treatment period
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Part 2: Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)
Time frame: Day 1 through Day 3 of each treatment period
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Part 2: Maximum observed plasma drug concentration (Cmax)
Time frame: Day 1 through Day 3 of each treatment period
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Part 2: Observed concentration at 24 hours post-dose (C24)
Time frame: Day 1 through Day 3 of each treatment period
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
6 secondary outcomes
Part 2: Time to reach peak or maximum observed concentration (tmax)
Time frame: Day 1 through Day 3 of each treatment period
Part 2: Terminal rate constant (λz)
Time frame: Day 1 through Day 3 of each treatment period
Part 2: Half life associated with λz (t½λz)
Time frame: Day 1 through Day 3 of each treatment period
Part 2: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
Time frame: Day 1 through Day 3 of each treatment period
Part 2: Volume of distribution at steady state following extravascular administration (Vz/F)
Time frame: Day 1 through Day 3 of each treatment period
Part 1 and Part 2: Number of adverse events and serious adverse events
Time frame: From Sceerning to Follow-up Visit approximately 40 days for Part 1 and 49 days for Part 2
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 23 Nov 2021.
- 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. All request 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.
Related trials for Chronic Kidney Disease
Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruiting
An Individuation Intervention to Reduce Socioeconomic Disparities in Chronic Kidney Disease Care
Chronic Kidney Diseases
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 (Treatment A), Dapagliflozin (Treatment A) and Zibotentan/Dapagliflozin - Formulation 1 (Treatment B) in people with Chronic Kidney Disease, 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 6 inclusion and 8 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 23 Nov 2021. 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?
Part 1: Metabolites in Safety Testing sampling (time frame: Day 1 through Day 6 (pre-dose, 30 min; 1, 2, 4, 6, 8, 12 and 24 hours post dose)). The study lists 5 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 23 Nov 2021.