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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01631097
First received: June 1, 2012
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Hepatic Impairment
Drug: Tivozanib hydrochloride
Phase 1

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

Further study details as provided by AVEO Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Maximum Observed Concentration (Cmax) [ Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose ] [ Designated as safety issue: No ]
  • Time to maximum concentration (Tmax) [ Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve from Hour 0 to the last measurable concentration (AUC0 t) [ Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve extrapolated to infinity (AUC0-∞) [ Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose ] [ Designated as safety issue: No ]
  • Apparent terminal elimination rate constant (λz) [ Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose ] [ Designated as safety issue: No ]
  • Apparent terminal elimination half-life (t1/2) [ Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose ] [ Designated as safety issue: No ]
  • Apparent total clearance (CL/F) [ Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose ] [ Designated as safety issue: No ]
  • Apparent volume of distribution (Vz/F) [ Time Frame: pre-dose, 1, 3, 5, 7, 10, 12, 18, 24, 36, 48, 96, 168, 336, and 504 hours postdose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: up to 16 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in vital signs [ Time Frame: Baseline and End of Study Visit (Day 30) ] [ Designated as safety issue: Yes ]
  • Change from baseline in physical examinations [ Time Frame: Baseline and End of Study Visit (Day 30) ] [ Designated as safety issue: Yes ]
  • Change from baseline in hematology including coagulation assessments [ Time Frame: Baseline and End of Study Visit (Day 30) ] [ Designated as safety issue: Yes ]
  • Change from baseline in chemistry assessments [ Time Frame: Baseline and End of Study Visit (Day 30) ] [ Designated as safety issue: Yes ]
  • Change from baseline in urinalysis assessments [ Time Frame: Baseline and End of Study Visit (Day 30) ] [ Designated as safety issue: Yes ]
  • Change from baseline in thyroid function tests [ Time Frame: Baseline and End of Study Visit (Day 30) ] [ Designated as safety issue: Yes ]
  • Change from baseline in electrocardiograms [ Time Frame: Baseline and End of Study Visit (Day 30) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 44
Study Start Date: May 2012
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Tivozanib hydrochloride
    Single oral capsule 1.5 mg tivozanib hydrochloride
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01631097

Locations
United States, Florida
Miami, Florida, United States
Orlando, Florida, United States
Sponsors and Collaborators
AVEO Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01631097     History of Changes
Other Study ID Numbers: AV-951-12-118
Study First Received: June 1, 2012
Last Updated: January 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on July 22, 2014