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

Phase 1
Completed
Conditions
Hepatic Impairment
Registration Number
NCT01631097
Lead Sponsor
AVEO Pharmaceuticals, Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
44
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
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
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
Secondary Outcome Measures
NameTimeMethod
Change from baseline in physical examinationsBaseline and End of Study Visit (Day 30)
Change from baseline in thyroid function testsBaseline and End of Study Visit (Day 30)
Change from baseline in electrocardiogramsBaseline 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 signsBaseline and End of Study Visit (Day 30)
Change from baseline in chemistry assessmentsBaseline and End of Study Visit (Day 30)
Change from baseline in urinalysis assessmentsBaseline and End of Study Visit (Day 30)
Change from baseline in hematology including coagulation assessmentsBaseline and End of Study Visit (Day 30)
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