A Phase 1, Open-label, Single Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Tivozanib in Subjects With Hepatic Impairment and Normal Hepatic Function
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- AVEO Pharmaceuticals, Inc.
- Enrollment
- 44
- Locations
- 2
- Primary Endpoint
- Apparent terminal elimination half-life (t1/2)
Study Overview
Brief Summary
This Phase 1, open-label, single dose study is designed to evaluate the pharmacokinetics, safety and tolerability of a single 1.5 mg tivozanib dose in subjects with varying degrees of hepatic impairment and normal hepatic function.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •BMI between 18 to 38 kg/m2
- •diagnosis of chronic or stable hepatic insufficiency, with a Child-Pugh classification scores of mild, moderate or severe.
Exclusion Criteria
- •Current or previous history of hepatic carcinoma, hepatorenal syndrome, portacaval shunt surgery, significant hepatic encephalopathy, severe ascites, or pleural effusion
- •Currently undergoing dialysis
- •Poor peripheral venous access
- •Pregnancy or lactation
Outcomes
Primary Outcomes
Apparent terminal elimination half-life (t1/2)
Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
Apparent total clearance (CL/F)
Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
Apparent volume of distribution (Vz/F)
Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
Maximum Observed Concentration (Cmax)
Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
Time to maximum concentration (Tmax)
Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
Area under the concentration-time curve from Hour 0 to the last measurable concentration (AUC0 t)
Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
Area under the concentration-time curve extrapolated to infinity (AUC0-∞)
Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
Apparent terminal elimination rate constant (λz)
Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
Secondary Outcomes
- Change from baseline in hematology including coagulation assessments(Baseline and End of Study Visit (Day 30))
- Change from baseline in physical examinations(Baseline and End of Study Visit (Day 30))
- Change from baseline in thyroid function tests(Baseline and End of Study Visit (Day 30))
- Change from baseline in electrocardiograms(Baseline and End of Study Visit (Day 30))
- Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)(up to 16 weeks)
- Change from baseline in vital signs(Baseline and End of Study Visit (Day 30))
- Change from baseline in chemistry assessments(Baseline and End of Study Visit (Day 30))
- Change from baseline in urinalysis assessments(Baseline and End of Study Visit (Day 30))