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

NCT04991571 | Completed Phase 1 FDA Drug

• 1 other identifier: D4325C00003
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Kidney Disease

Outcome Measures

Primary Outcomes (5)

• 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)

• 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

• 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

• 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

• 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 Outcomes (6)

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

  Day 1 through Day 3 of each treatment period

• Part 2: Terminal rate constant (λz)

  Day 1 through Day 3 of each treatment period

• Part 2: Half life associated with λz (t½λz)

  Day 1 through Day 3 of each treatment period

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

  Day 1 through Day 3 of each treatment period

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

  Day 1 through Day 3 of each treatment period

Study Arms (4)

Part 1

EXPERIMENTAL

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

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.

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.

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.

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

Interventions

Zibotentan (Treatment A) DRUG

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

Part 1; Part 2: Treatment Sequence ABC; Part 2: Treatment Sequence BCA; Part 2: Treatment Sequence CAB

Dapagliflozin (Treatment A) DRUG

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

Part 2: Treatment Sequence ABC; Part 2: Treatment Sequence BCA; Part 2: Treatment Sequence CAB

Zibotentan/Dapagliflozin - Formulation 1 (Treatment B) DRUG

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

Part 2: Treatment Sequence ABC; Part 2: Treatment Sequence BCA; Part 2: Treatment Sequence CAB

Zibotentan/Dapagliflozin - Formulation 2 (Treatment C) DRUG

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

Part 2: Treatment Sequence ABC; Part 2: Treatment Sequence BCA; Part 2: Treatment Sequence CAB

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• \. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
• \. 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Brooklyn, Maryland, 21225, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

ZD4054; dapagliflozin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2021
• First Posted: August 5, 2021
• Study Start: July 29, 2021
• Primary Completion: October 22, 2021
• Study Completion: October 22, 2021
• Last Updated: November 23, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

US (1)