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

Hepatic Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01631097
• Other study ID #: AV-951-12-118
• Status: Completed
• Phase: Phase 1
• First received: June 1, 2012
• Last updated: January 23, 2014
• Start date: May 2012
• Est. completion date: January 2014

Study information

• Verified date: January 2014
• Source: AVEO Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Tivozanib hydrochloride
Single oral capsule 1.5 mg tivozanib hydrochloride

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
AVEO Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Concentration (Cmax)		pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose	No
Primary	Time to maximum concentration (Tmax)		pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose	No
Primary	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	No
Primary	Area under the concentration-time curve extrapolated to infinity (AUC0-8)		pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose	No
Primary	Apparent terminal elimination rate constant (?z)		pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose	No
Primary	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	No
Primary	Apparent total clearance (CL/F)		pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose	No
Primary	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	No
Secondary	Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)		up to 16 weeks	Yes
Secondary	Change from baseline in vital signs		Baseline and End of Study Visit (Day 30)	Yes
Secondary	Change from baseline in physical examinations		Baseline and End of Study Visit (Day 30)	Yes
Secondary	Change from baseline in hematology including coagulation assessments		Baseline and End of Study Visit (Day 30)	Yes
Secondary	Change from baseline in chemistry assessments		Baseline and End of Study Visit (Day 30)	Yes
Secondary	Change from baseline in urinalysis assessments		Baseline and End of Study Visit (Day 30)	Yes
Secondary	Change from baseline in thyroid function tests		Baseline and End of Study Visit (Day 30)	Yes
Secondary	Change from baseline in electrocardiograms		Baseline and End of Study Visit (Day 30)	Yes