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

NCT ID: NCT04991571

Last Updated: 2021-11-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-29

Study Completion Date

2021-10-22

Brief Summary

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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

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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

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Chronic Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1

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

Group Type EXPERIMENTAL

Zibotentan (Treatment A)

Intervention Type DRUG

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

Part 2: Treatment Sequence ABC

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.

Group Type EXPERIMENTAL

Zibotentan (Treatment A)

Intervention Type DRUG

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

Dapagliflozin (Treatment A)

Intervention Type DRUG

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

Zibotentan/Dapagliflozin - Formulation 1 (Treatment B)

Intervention Type DRUG

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

Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)

Intervention Type DRUG

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

Part 2: Treatment Sequence BCA

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.

Group Type EXPERIMENTAL

Zibotentan (Treatment A)

Intervention Type DRUG

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

Dapagliflozin (Treatment A)

Intervention Type DRUG

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

Zibotentan/Dapagliflozin - Formulation 1 (Treatment B)

Intervention Type DRUG

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

Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)

Intervention Type DRUG

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

Part 2: Treatment Sequence CAB

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.

Group Type EXPERIMENTAL

Zibotentan (Treatment A)

Intervention Type DRUG

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

Dapagliflozin (Treatment A)

Intervention Type DRUG

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

Zibotentan/Dapagliflozin - Formulation 1 (Treatment B)

Intervention Type DRUG

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

Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)

Intervention Type DRUG

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

Interventions

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Zibotentan (Treatment A)

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

Intervention Type DRUG

Dapagliflozin (Treatment A)

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

Intervention Type DRUG

Zibotentan/Dapagliflozin - Formulation 1 (Treatment B)

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

Intervention Type DRUG

Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)

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

Intervention Type DRUG

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Brooklyn, Maryland, United States

Site Status

Countries

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United States

Other Identifiers

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D4325C00003

Identifier Type: -

Identifier Source: org_study_id