Clinical trial NCT04991571: Study to Collect Samples for MIST Analysis of Zibotentan and Bioavailability of Zibotentan and Dapagliflozin in Heatlhy Participants
Official title: A Phase 1, Open-label Study With Two Independent Parts: Collecting Samples for Metabolites in Safety Testing Analysis of Zibotentan After Repeated Administration (Part 1); and a Randomised, Cross-over, Three Period, Three-treatment, Single Dose Study to Assess the Relative Bioavailability of Different Formulations of Zibotentan and Dapagliflozin (Part 2) in Healthy Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Kidney Disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-08-05
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

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

8. 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.

Primary outcomes:
measure: Part 1: Metabolites in Safety Testing sampling
timeFrame: Day 1 through Day 6 (pre-dose, 30 min; 1, 2, 4, 6, 8, 12 and 24 hours post dose)
measure: Part 2: Area under plasma concentration time curve from zero to infinity (AUCinf)
timeFrame: Day 1 through Day 3 of each treatment period
measure: Part 2: Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)
timeFrame: Day 1 through Day 3 of each treatment period
measure: Part 2: Maximum observed plasma drug concentration (Cmax)
timeFrame: Day 1 through Day 3 of each treatment period
measure: Part 2: Observed concentration at 24 hours post-dose (C24)
timeFrame: Day 1 through Day 3 of each treatment period
Secondary outcomes:
measure: Part 2: Time to reach peak or maximum observed concentration (tmax)
timeFrame: Day 1 through Day 3 of each treatment period
measure: Part 2: Terminal rate constant (λz)
timeFrame: Day 1 through Day 3 of each treatment period
measure: Part 2: Half life associated with λz (t½λz)
timeFrame: Day 1 through Day 3 of each treatment period
measure: Part 2: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
timeFrame: Day 1 through Day 3 of each treatment period
measure: Part 2: Volume of distribution at steady state following extravascular administration (Vz/F)
timeFrame: Day 1 through Day 3 of each treatment period
measure: Part 1 and Part 2: Number of adverse events and serious adverse events
timeFrame: From Sceerning to Follow-up Visit approximately 40 days for Part 1 and 49 days for Part 2
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: Research Site
state: Maryland
Study officials:
References: