A study to assess the Pharmacokinetics (PK) of combined oral ethinyl estradiol (EE) and levonorgestrel (LNG) in healthy female participants of non-child-bearing potential, when administered alone and in combination with multiple oral doses of zibotentan.
This is an open-label, single-sequence study conducted at a single study center. The study will comprise of the following: * A Screening Period (Visit 1) of maximum 28 days (Day -28 to Day -2). * Treatment Period 1/Day 1 to Day 5 (in-house stay): Participants will check in at the clinical unit on Day -1 and will be resident at the clinical unit until Day 6. * Treatment Period 2/Day 6 to Day 14 (home): Outpatient period. * Treatment Period 3/Day 15 to Day 20 (in-house stay): On the evening of Day 14, the participants will check in at the clinical unit and will be resident at the clinical unit until Day 20. * A follow-up visit (Day 27) will be conducted 7 days (±2 days) after the last PK sample collection (120 hours post-dose \[Day 20\]). Participants will receive two tablets of EE/LNG on days 1 and 15 and 2 capsules of zibotentan on days 6-19.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Participants will receive two capsules of Zibotentan orally QD from day 6-19.
Participants will receive two tablets of EE and LNG once on Day 1 and Day 15 as a combined oral dose.
Research Site
Brooklyn, Maryland, United States
Area under plasma concentration time curve from zero to infinity (AUCinf)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Time frame: Day 1 and Day 15
Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Time frame: Day 1 and Day 15
Maximum observed plasma (peak) drug concentration (Cmax)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Time frame: Day 1 and Day 15
Terminal elimination half-life (t1/2λz)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Time frame: Day 1 and Day 15
Time to reach maximum observed concentration (tmax)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Time frame: Day 1 and Day 15
Apparent total body clearance of drug from plasma (CL/F)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Time frame: Day 1 and Day 15
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Apparent volume of distribution based on terminal phase (Vz/F)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Time frame: Day 1 and Day 15
Area under plasma concentration-time curve in the dose interval (AUCtau)
The PK of zibotentan in healthy female volunteers of non-child-bearing potential will be assessed.
Time frame: Day 15
Maximum observed plasma (peak) drug concentration (Cmax)
The PK of zibotentan in healthy female volunteers of non-child-bearing potential will be assessed.
Time frame: Day 15
Time to reach maximum observed concentration (tmax)
The PK of zibotentan in healthy female volunteers of non-child-bearing potential will be assessed.
Time frame: Day 15
Number of participants with adverse events
The safety and tolerability of zibotentan alone and in combination with combined oral EE and LNG will be examined.
Time frame: Until Follow up visit (7 days +/-2 days after last PK sample)