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

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Chronic Kidney Disease

Treatments: Drug: Zibotentan (Treatment A); Drug: Dapagliflozin (Treatment A); Drug: Zibotentan/Dapagliflozin - Formulation 1 (Treatment B); Drug: Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04991571

D4325C00003

Details and patient eligibility

About

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.

Full 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.

Enrollment: 27 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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.

6. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.

7. 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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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27 participants in 4 patient groups

Part 1

Experimental group

Description:

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

Treatment:

Drug: Zibotentan (Treatment A)

Part 2: Treatment Sequence ABC

Experimental group

Description:

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.

Treatment:

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 group

Description:

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.

Treatment:

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 group

Description:

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.

Treatment:

Drug: Zibotentan (Treatment A)

Drug: Dapagliflozin (Treatment A)

Drug: Zibotentan/Dapagliflozin - Formulation 1 (Treatment B)

Drug: Zibotentan/Dapagliflozin - Formulation 2 (Treatment C)