A Single-Dose Study of Tivozanib in Subjects With Hepatic Impairment and Normal Hepatic Function

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: Tivozanib hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tivozanib hydrochloride|Single oral capsule 1.5 mg tivozanib hydrochloride|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) |  | pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose | 
| Time to maximum concentration (Tmax) |  | 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) |  | 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-∞) |  | 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) |  | pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose | 
| Apparent terminal elimination half-life (t1/2) |  | pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose | 
| Apparent total clearance (CL/F) |  | 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) |  | pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 physical examinations |  | Baseline and End of Study Visit (Day 30) | 
| Change from baseline in hematology including coagulation assessments |  | 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) | 
| 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) |