This study aim to assess the Pharmacokinetics of Zibotentan in Healthy Non-Asian and Japanese Participants.
This study will be Phase I, randomized, open-label, single-dose, 4-period, 4-treatment, cross-over study, performed at a single study center. The study will comprise: Screening Period of maximum 28 days; Four Treatment Periods, separated by 3 washout periods; Final Follow-up Visit within 5 to 7 days after the last study intervention administration. The washout periods will last at least 3 days, resulting in a total dosing-free time of at least 6 full days between each of the 4 treatments. Participant will receive the first dose is on Day 1, then the next dose will be on Day 8 at the earliest. Each participant will receive 4 different single doses (Dose 1, 2, 3 and 4) of zibotentan, at all 4 studied dose levels in one of the following treatment sequences: ABCD, BDAC, CADB, DCBA. Each participant will be involved in the study for approximately 9 weeks, depending upon the duration of the washout periods.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Participant will receive 4 different single doses of zibotentan on Day 1 of each treatment period orally.
Research Site
Glendale, California, United States
Area under concentration-time curve from time 0 to infinity (AUCinf)
To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants.
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants.
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Maximum observed drug concentration (Cmax)
To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Number of participants with adverse events (AEs) receiving single dose
To assess the safety and tolerability of receiving single dose of orally administered zibotentan.
Time frame: From Screening (28 days) to follow-up Visit 5 to 7 days post-final dose (approximately 9 weeks)
Concentration at 24 hours post dose (C24)
To further characterize zibotentan PK in plasma.
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Partial area under the concentration time curve from time 0 to 24 hours post-dose (AUC(0-24))
To further characterize zibotentan PK in plasma.
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
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Time to reach maximum observed concentration (tmax)
To further characterize zibotentan PK in plasma.
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Terminal elimination half-life (t1/2 λz)
To further characterize zibotentan PK in plasma.
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Mean residence time (MRTinf)
To further characterize zibotentan PK in plasma.
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Terminal rate constant (λz)
To further characterize zibotentan PK in plasma.
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Apparent total body clearance (CL/F)
To further characterize zibotentan PK in plasma.
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Apparent volume of distribution based on the terminal phase (Vz/F)
To further characterize zibotentan PK in plasma.
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Individual and cumulative amount of unchanged drug excreted into urine (Ae) (by time point and cumulative)
To further characterize zibotentan PK in urine.
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 (fe) (by time point and cumulative)
To further characterize zibotentan PK in urine.
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)
Renal clearance (CLR)
To further characterize zibotentan PK in urine.
Time frame: Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)