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INC280 in Healthy Subjects With Impaired Hepatic Function and Subjects With Normal Hepatic Function

Phase 1
Completed
Conditions
Hepatic Impairment
Interventions
Drug: INC280
Registration Number
NCT02474537
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

This is a phase I, multi-center, open-label, single oral dose, parallel group study to evaluate the pharmacokinetics and safety of INC280 in non-cancer subjects with impaired hepatic function and non-cancer subjects with normal hepatic function.The study population will be healthy male and postmenopausal or sterile female subjects who meet all of the inclusion and none of the exclusion criteria. Subjects will be assigned to groups according to their hepatic function: normal (Group 1), mild (Group 2), moderate (Group 3), and severe (Group 4) impairment. This study consists of a two-staged design with interim analysis. In Stage 1, subjects in Groups 1, 2 and 3 will be enrolled. Upon completion of Stage 1, an interim analysis will be conducted. Depending on the results of the analysis, either the study will conclude with no further enrollment or Stage 2 will commence with enrollment of Group 4.

A minimum of 6 evaluable subjects per group will be enrolled.Once enrolled in the study, participants will be confined to the facility for 4 days, given a single dose of INC280 and monitored for pharmacokinetic and safety assessments.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
31
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Mild hepatic impairmentINC280Subjects with mild hepatic impairment
Moderate hepatic impairmentINC280Subjects with moderate hepatic impairment
Normal hepatic functionINC280Subjects with normal hepatic function
Severe hepatic impairmentINC280Subjects with severe hepatic impairment
Primary Outcome Measures
NameTimeMethod
AUClast of INC280Up to 72 hours post-dose

INC280 pharmacokinetic parameters

AUCinf of INC280Up to 72 hours post-dose

INC280 pharmacokinetic parameters

Cmax of INC280Up to 72 hours post-dose

INC280 pharmacokinetic parameters

Tmax of INC280Up to 72 hours post-dose

INC280 pharmacokinetic parameters

T1/2 of INC280Up to 72 hours post-dose

INC280 pharmacokinetic parameters

CL/F of INC280Up to 72 hours post-dose

INC280 pharmacokinetic parameters

Vz/F of INC280Up to 72 hours post-dose

INC280 pharmacokinetic parameters

Secondary Outcome Measures
NameTimeMethod
Unbound fraction and T1/2 based on unbound concentration in plasma3 hours post-dose

To assess the plasma protein binding of INC280

Unbound fraction and CL/F based on unbound concentration in plasma3 hours post-dose

To assess the plasma protein binding of INC280

Unbound fraction and Vz/F based on unbound concentration in plasma3 hours post-dose

To assess the plasma protein binding of INC280

Adverse events based on the CTCAE v4.03 grade (severity) and frequency, and other safety data (e.g., ECG, laboratory results)Up to 30 days

Safety

Unbound fraction and AUClast based on unbound concentration in plasma3 hours post-dose

To assess the plasma protein binding of INC280

Unbound fraction and AUCinf based on unbound concentration in plasma3 hours post-dose

To assess the plasma protein binding of INC280

Unbound fraction and Cmax based on unbound concentration in plasma3 hours post-dose

To assess the plasma protein binding of INC280

Unbound fraction and Tmax based on unbound concentration in plasma3 hours post-dose

To assess the plasma protein binding of INC280

Trial Locations

Locations (5)

Orlando Clinical Research Center

🇺🇸

Orlando, Florida, United States

Clinical Pharmacology of Miami, LLC.

🇺🇸

Miami, Florida, United States

DaVita Clinical Research

🇺🇸

Minneapolis, Minnesota, United States

Duke University Medical Center Oncology

🇺🇸

Durham, North Carolina, United States

University of Miami Miller School of Medicine Clinical Resea Oncology

🇺🇸

Miami, Florida, United States

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