Study to Collect Samples for MIST Analysis of Zibotentan and Bioavailability of Zibotentan and Dapagliflozin in Heatlhy Participants

Chronic Kidney Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04991571
• Other study ID #: D4325C00003
• Status: Completed
• Phase: Phase 1
• Start date: July 29, 2021
• Est. completion date: October 22, 2021

Study information

• Verified date: November 2021
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: October 22, 2021
• Est. primary completion date: October 22, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

For inclusion in the study participants should fulfil the following criteria:

1. Participants with suitable veins for cannulation or repeated venipuncture.

2. 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

3. Male participant must adhere to the contraception methods.

4. 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.

5. Provision of signed and dated, written informed consent prior to any study specific procedures.

Exclusion Criteria:

Participants will not enter the study if any of the following exclusion criteria are fulfilled:

1. History or presence of gastrointestinal, hepatic or renal disease or any important disease or disorder.

2. Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study intervention.

3. Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis.

4. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and Human immunodeficiency virus antibody.

5. 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.

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Zibotentan (Treatment A)
Zibotentan capsule will be administered orally as multiple doses in Part 1 and as single dose in Part 2.
• Dapagliflozin (Treatment A)
Dapagliflozin tablet will be administered orally as single dose in Part 2.
• Zibotentan/Dapagliflozin - Formulation 1 (Treatment B)
Zibotentan/Dapagliflozin tablet will be administered orally as single dose in Part 2.
• Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)
Zibotentan/Dapagliflozin tablet will be administered orally as single dose in Part 2.

Locations

Country	Name	City	State
United States	Research Site	Brooklyn	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1 through Day 6 (pre-dose, 30 min; 1, 2, 4, 6, 8, 12 and 24 hours post dose)
Primary	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.	Day 1 through Day 3 of each treatment period
Primary	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.	Day 1 through Day 3 of each treatment period
Primary	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.	Day 1 through Day 3 of each treatment period
Primary	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.	Day 1 through Day 3 of each treatment period
Secondary	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.	Day 1 through Day 3 of each treatment period
Secondary	Part 2: Terminal rate constant (?z)	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.	Day 1 through Day 3 of each treatment period
Secondary	Part 2: Half life associated with ?z (t½?z)	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.	Day 1 through Day 3 of each treatment period
Secondary	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.	Day 1 through Day 3 of each treatment period
Secondary	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.	Day 1 through Day 3 of each treatment period
Secondary	Part 1 and Part 2: Number of adverse events and serious adverse events	Safety and tolerability of zibotentan and dapagliflozin will be studied.	From Sceerning to Follow-up Visit approximately 40 days for Part 1 and 49 days for Part 2