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

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).

• Zibotentan/Dapagliflozin FDC (Drug): Zibotentan/Dapagliflozin FDC will be administered as an oral tablet.

Primary outcomes

• Area under concentration-time curve from time 0 to infinity (AUCinf) [At predefined intervals from Day 1 to Day 4 for both treatment periods]: 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.
• Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) [At predefined intervals from Day 1 to Day 4 for both treatment periods]: 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.
• Maximum observed drug concentration (Cmax) [At predefined intervals from Day 1 to Day 4 for both treatment periods]: 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.

Secondary outcomes

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

Sex: All, ages: 18 Years to 60 Years, accepts healthy volunteers

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.