A Study to Investigate the Concentrations of Zibotentan and Dapagliflozin in Blood When Given With and Without Food

A Randomized, Single Dose, Crossover Study to Assess the Effect of Food on the Pharmacokinetics of Single Dose, Orally Administered, Combined Zibotentan/Dapagliflozin in Healthy Participants

The purpose of this study is to investigate the concentrations of zibotentan and dapagliflozin in blood when given with and without food in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Zibotentan/Dapagliflozin FDC

Detailed Description

This is a Phase I, open-label, randomized, 2-period, 2-treatment, crossover study in healthy participants.

This study will measure the impact of food on the pharmacokinetics (PK) of combined zibotentan/dapagliflozin for the to be marketed fixed-dose combination (FDC) formulation (study intervention).

The study will comprise of, (i) A screening period (ii) 2 treatment periods (iii) A final follow-up visit.

All participants will receive a single dose of the study intervention once under fasted condition (Treatment A) and once under fed condition (Treatment B).

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy male and/or female of non-childbearing potential. Participants with suitable veins for cannulation or repeated venipuncture.
• Have a body mass index (BMI) between 18 and 32 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg (inclusive) at Screening.

Exclusion Criteria:

• History of any clinically important disease or disorder.
• History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically important illness, medical/surgical procedure, or trauma.
• Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results or other laboratory values or vital signs.
• Any positive result on screening for serum Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis C virus (HCV) antibody, or Human immunodeficiency virus (HIV) (Type 1 and 2) antibodies.
• Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
• History or ongoing allergy/hypersensitivity, to Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i- eg, dapagliflozin, empagliflozin), or zibotentan or other Endothelin Receptor Antagonist (ERAs- eg, ambrisentan, atrasentan,bosentan), or any of the excipients in the zibotentan/dapagliflozin tablets.
• Participants who have previously received zibotentan.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment AB; Participants will receive single dose of Zibotentan/Dapagliflozin FDC after an overnight fast of at least 10 hours (Treatment A). After a washout period, participants will receive another single dose of Zibotentan/Dapagliflozin FDC 30 minutes after having a high-fat, high-calorie standardized meal (Treatment B).	Drug: Zibotentan/Dapagliflozin FDC; Zibotentan/Dapagliflozin FDC will be administered as an oral tablet.
Experimental: Treatment BA; Participants will receive single dose of Zibotentan/Dapagliflozin FDC 30 minutes after having a high-fat high-calorie standardized meal (Treatment B). After a washout period, participants will receive another single dose of Zibotentan/Dapagliflozin FDC after an overnight fast of at least 10 hours (Treatment A).	Drug: Zibotentan/Dapagliflozin FDC; Zibotentan/Dapagliflozin FDC will be administered as an oral tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under concentration-time curve from time 0 to infinity (AUCinf)	To investigate the effect of a high fat, high calorie meal, in comparison to fasting conditions, on the PK of zibotentan/dapagliflozin FDC after a single oral dose in healthy participants.	At predefined intervals from Day 1 to Day 4 for both treatment periods
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)	To investigate the effect of a high fat, high calorie meal, in comparison to fasting conditions, on the PK of zibotentan/dapagliflozin FDC after a single oral dose in healthy participants.	At predefined intervals from Day 1 to Day 4 for both treatment periods
Maximum observed drug concentration (Cmax)	To investigate the effect of a high fat, high calorie meal, in comparison to fasting conditions, on the PK of zibotentan/dapagliflozin FDC after a single oral dose in healthy participants.	At predefined intervals from Day 1 to Day 4 for both treatment periods

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs) and serious adverse events (SAEs)	To further assess the safety and tolerability of single doses of zibotentan/dapagliflozin FDC in healthy participants.	Up to end of study visit, for a total of approximately 5 weeks
Apparent total body clearance (CL/F)	To further evaluate the PK of zibotentan/dapagliflozin FDC after a single oral dose in healthy participants.	At predefined intervals from Day 1 to Day 4 for both treatment periods
Apparent volume of distribution based on the terminal phase (Vz/F)	To further evaluate the PK of zibotentan/dapagliflozin FDC after a single oral dose in healthy participants.	At predefined intervals from Day 1 to Day 4 for both treatment periods
Time to reach maximum observed concentration (tmax)	To further evaluate the PK of zibotentan/dapagliflozin FDC after a single oral dose in healthy participants.	At predefined intervals from Day 1 to Day 4 for both treatment periods
Terminal elimination half-life (t½λz)	To further evaluate the PK of zibotentan/dapagliflozin FDC after a single oral dose in healthy participants.	At predefined intervals from Day 1 to Day 4 for both treatment periods

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2026
• Primary Completion (Actual): April 2, 2026
• Study Completion (Actual): April 2, 2026

Study Registration Dates

• First Submitted: February 5, 2026
• First Submitted That Met QC Criteria: February 5, 2026
• First Posted (Actual): February 11, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Food effect; Chronic kidney disease; Fixed-dose combination
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Renal Insufficiency, Chronic; ZD4054
• Other Study ID Numbers: D4327C00003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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 Vivli.org. All requests 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 PhRMA 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 anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No