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

NCT01631097 | Completed Phase 1

• 1 other identifier: AV-951-12-118
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

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.

Conditions

Hepatic Impairment

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (8)

• 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)

Interventions

Tivozanib hydrochloride DRUG

Single oral capsule 1.5 mg tivozanib hydrochloride

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (2)

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

Orlando, Florida, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2012
• First Posted: June 28, 2012
• Study Start: May 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: January 27, 2014

Record last verified: 2014-01

Locations

US (2)