Back to results

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

Primary Purpose

Chronic Kidney Disease

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Zibotentan (Treatment A)

Dapagliflozin (Treatment A)

Zibotentan/Dapagliflozin - Formulation 1 (Treatment B)

Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)

About this trial

This is an interventional treatment trial for Chronic Kidney Disease

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Part 1

Part 2: Treatment Sequence ABC

Part 2: Treatment Sequence BCA

Part 2: Treatment Sequence CAB

Arm Description

Participants will be administered with zibotentan once daily for 5 days.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

Part 1 and Part 2: Number of adverse events and serious adverse events

Safety and tolerability of zibotentan and dapagliflozin will be studied.

Full Information

NCT ID

NCT04991571

First Posted

July 28, 2021

Last Updated

November 22, 2021

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT04991571

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Completed

Study Start Date

July 29, 2021 (Actual)

Primary Completion Date

October 22, 2021 (Actual)

Study Completion Date

October 22, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Kidney Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1

Arm Type

Experimental

Arm Description

Participants will be administered with zibotentan once daily for 5 days.

Arm Title

Part 2: Treatment Sequence ABC

Arm Type

Experimental

Arm Description

Arm Title

Part 2: Treatment Sequence BCA

Arm Type

Experimental

Arm Description

Arm Title

Part 2: Treatment Sequence CAB

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Zibotentan (Treatment A)

Intervention Description

Zibotentan capsule will be administered orally as multiple doses in Part 1 and as single dose in Part 2.

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin (Treatment A)

Intervention Description

Dapagliflozin tablet will be administered orally as single dose in Part 2.

Intervention Type

Drug

Intervention Name(s)

Zibotentan/Dapagliflozin - Formulation 1 (Treatment B)

Intervention Description

Zibotentan/Dapagliflozin tablet will be administered orally as single dose in Part 2.

Intervention Type

Drug

Intervention Name(s)

Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)

Intervention Description

Zibotentan/Dapagliflozin tablet will be administered orally as single dose in Part 2.

Primary Outcome Measure Information:

Title

Part 1: Metabolites in Safety Testing sampling

Description

Plasma sample will be collected to understand the PK profiling of zibotentan metabolites and to meet the regulatory requirements.

Time Frame

Day 1 through Day 6 (pre-dose, 30 min; 1, 2, 4, 6, 8, 12 and 24 hours post dose)

Title

Part 2: Area under plasma concentration time curve from zero to infinity (AUCinf)

Description

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.

Time Frame

Day 1 through Day 3 of each treatment period

Title

Part 2: Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)

Description

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.

Time Frame

Day 1 through Day 3 of each treatment period

Title

Part 2: Maximum observed plasma drug concentration (Cmax)

Description

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.

Time Frame

Day 1 through Day 3 of each treatment period

Title

Part 2: Observed concentration at 24 hours post-dose (C24)

Description

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.

Time Frame

Day 1 through Day 3 of each treatment period

Secondary Outcome Measure Information:

Title

Part 2: Time to reach peak or maximum observed concentration (tmax)

Description

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.

Time Frame

Day 1 through Day 3 of each treatment period

Title

Part 2: Terminal rate constant (λz)

Description

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.

Time Frame

Day 1 through Day 3 of each treatment period

Title

Part 2: Half life associated with λz (t½λz)

Description

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.

Time Frame

Day 1 through Day 3 of each treatment period

Title

Part 2: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)

Description

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.

Time Frame

Day 1 through Day 3 of each treatment period

Title

Part 2: Volume of distribution at steady state following extravascular administration (Vz/F)

Description

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.

Time Frame

Day 1 through Day 3 of each treatment period

Title

Part 1 and Part 2: Number of adverse events and serious adverse events

Description

Safety and tolerability of zibotentan and dapagliflozin will be studied.

Time Frame

From Sceerning to Follow-up Visit approximately 40 days for Part 1 and 49 days for Part 2

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Facility Information:

Facility Name

Research Site

City

Brooklyn

State/Province

Maryland

ZIP/Postal Code

21225

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing URL

https://astrazenecagroup-dt.pharmacm.com/DT/Home

Learn more about this trial

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

We'll reach out to this number within 24 hrs