This study will evaluate the pharmacokinetics (PK), safety, and tolerability of a single oral dose of zibotentan in patients with moderate hepatic and moderate renal impairment in comparison to a matched healthy control group.
This is a single-dose, non-randomised, open-label, parallel-group study. All participants will receive a single oral dose of 5 mg zibotentan under fasted conditions and will be involved in the study for approximately 5 weeks. Approximately 12 participants will be enrolled into each one of the 2 cohorts and receive the study intervention: * Cohort 1: 12 participants with moderate hepatic impairment and moderate renal impairment as assessed at Screening * Cohort 2: 12 healthy participants matched for age (± 10 years), gender, and BMI (± 20%) on a group level to participants in Cohort 1 The study will comprise of the following study periods: * A Screening Period of maximum 28 days (before dosing): participants will be screened for eligibility. * A Residential Period of 8 days: participants will be admitted to the study centre in the evening on Day * 2, two days before administration of a single oral dose of zibotentan (Day 1). Participants will have final study assessments on Day 6 (120 hours post-dose) and will be discharged that day.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
All participants will receive a single oral dose of zibotentan capsule under fasted conditions.
Research Site
Sofia, Bulgaria
Area under plasma concentration-time curve from time zero to infinity (AUCinf)
To assess the PK of a single oral dose of zibotentan in participants with moderate hepatic impairment and moderate renal impairment compared to a group of healthy matched controls
Time frame: Day 1 to Day 6
Area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUClast)
To assess the PK of a single oral dose of zibotentan in participants with moderate hepatic impairment and moderate renal impairment compared to a group of healthy matched controls
Time frame: Day 1 to Day 6
Maximum observed plasma concentration (Cmax)
To assess the PK of a single oral dose of zibotentan in participants with moderate hepatic impairment and moderate renal impairment compared to a group of healthy matched controls
Time frame: Day 1 to Day 6
Number of participants with adverse events
To evaluate the safety and tolerability of a single oral dose of zibotentan in participants with moderate hepatic impairment and moderate renal impairment compared to a group of healthy matched controls
Time frame: Screening (Day -28 to Day -2) to Day 6
Time to reach maximum observed plasma concentration (tmax)
To further characterise zibotentan plasma PK in all treatment groups
Time frame: Day 1 to Day 6
Area under the plasma concentration-time curve from time zero to 24 hours post-dose (AUC[0-24])
To further characterise zibotentan plasma PK in all treatment groups
Time frame: Day 1 to Day 6
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Area under plasma concentration-time curve from time zero to 72 hours post-dose (AUC [0-72])
To further characterise zibotentan plasma PK in all treatment groups
Time frame: Day 1 to Day 6
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)
To further characterise zibotentan plasma PK in all treatment groups
Time frame: Day 1 to Day 6
Terminal elimination rate constant (λz)
To further characterise zibotentan plasma PK in all treatment groups
Time frame: Day 1 to Day 6
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
To further characterise zibotentan plasma PK in all treatment groups
Time frame: Day 1 to Day 6
Apparent total non-renal body clearance of drug from plasma after extravascular administration (CLNR/F)
To further characterise zibotentan plasma PK in all treatment groups
Time frame: Day 1 to Day 6
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
To further characterise zibotentan plasma PK in all treatment groups
Time frame: Day 1 to Day 6
Amount of unchanged drug excreted into urine from time t1 to time t2 [Ae (t1-t2)]
To further characterise zibotentan urine PK in all treatment groups
Time frame: Day 1 to Day 3
Cumulative amount of unchanged drug excreted into urine from time of dosing (time 0) through time t [Ae (0-t)]
To further characterise zibotentan urine PK in all treatment groups
Time frame: Day 1 to Day 3
Percentage of dose excreted unchanged in urine from time t1 to time t2 [fe (t1-t2)]
To further characterise zibotentan urine PK in all treatment groups
Time frame: Day 1 to Day 3
Percentage of dose excreted unchanged in urine from time of dosing (time 0) through time t [fe (0-t)]
To further characterise zibotentan urine PK in all treatment groups
Time frame: Day 1 to Day 3
Renal clearance of drug from plasma, calculated as Ae0-t/AUC0-t where t is matched for urine and plasma (CLR)
To further characterise zibotentan urine PK in all treatment groups
Time frame: Day 1 to Day 3