Clinical trial NCT01631097: A Single-Dose Study of Tivozanib in Subjects With Hepatic Impairment and Normal Hepatic Function
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Lead sponsor: AVEO Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-06-28
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Observed Concentration (Cmax)
timeFrame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
measure: Time to maximum concentration (Tmax)
timeFrame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
measure: Area under the concentration-time curve from Hour 0 to the last measurable concentration (AUC0 t)
timeFrame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
measure: Area under the concentration-time curve extrapolated to infinity (AUC0-∞)
timeFrame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
measure: Apparent terminal elimination rate constant (λz)
timeFrame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
measure: Apparent terminal elimination half-life (t1/2)
timeFrame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
measure: Apparent total clearance (CL/F)
timeFrame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
measure: Apparent volume of distribution (Vz/F)
timeFrame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose
Secondary outcomes:
measure: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: up to 16 weeks
measure: Change from baseline in vital signs
timeFrame: Baseline and End of Study Visit (Day 30)
measure: Change from baseline in physical examinations
timeFrame: Baseline and End of Study Visit (Day 30)
measure: Change from baseline in hematology including coagulation assessments
timeFrame: Baseline and End of Study Visit (Day 30)
measure: Change from baseline in chemistry assessments
timeFrame: Baseline and End of Study Visit (Day 30)
measure: Change from baseline in urinalysis assessments
timeFrame: Baseline and End of Study Visit (Day 30)
measure: Change from baseline in thyroid function tests
timeFrame: Baseline and End of Study Visit (Day 30)
measure: Change from baseline in electrocardiograms
timeFrame: Baseline and End of Study Visit (Day 30)
Other outcomes:
Locations:
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
Study officials:
References: