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

Study Timeline

• Study Start: 2012-05
• Study First Submitted: 2012-06-01
• Study First Submitted QC: 2012-06-27
• Study First Posted: 2012-06-28
• Status Verified: 2014-01
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Last Update Submitted: 2014-01-23
• Last Update Posted: 2014-01-27

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

Name	Time	Method
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

Name	Time	Method
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)
Change from baseline in hematology including coagulation assessments	Baseline and End of Study Visit (Day 30)