Healthy Participants
Conditions
Keywords
Chronic kidney disease, Pharmacokinetics, Food effect, Fixed-dose combination
Brief summary
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.
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).
Interventions
DRUGZibotentan/Dapagliflozin FDC
Zibotentan/Dapagliflozin FDC will be administered as an oral tablet.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed