An Open Label, Single-dose, Multi-center, Parallel-group, Two-staged Study to Evaluate Pharmacokinetics of Oral cMET Inhibitor INC280 in Non-Cancer Subjects With Impaired Hepatic Function and Non-Cancer Subjects With Normal Hepatic Function
Overview
- Phase
- Phase 1
- Intervention
- INC280
- Conditions
- Hepatic Impairment
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 31
- Locations
- 5
- Primary Endpoint
- AUClast of INC280
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Normal hepatic function
Subjects with normal hepatic function
Intervention: INC280
Mild hepatic impairment
Subjects with mild hepatic impairment
Intervention: INC280
Moderate hepatic impairment
Subjects with moderate hepatic impairment
Intervention: INC280
Severe hepatic impairment
Subjects with severe hepatic impairment
Intervention: INC280
Outcomes
Primary Outcomes
AUClast of INC280
Time Frame: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
AUCinf of INC280
Time Frame: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
CL/F of INC280
Time Frame: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Vz/F of INC280
Time Frame: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Cmax of INC280
Time Frame: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Tmax of INC280
Time Frame: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
T1/2 of INC280
Time Frame: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Secondary Outcomes
- Unbound fraction and T1/2 based on unbound concentration in plasma(3 hours post-dose)
- Unbound fraction and CL/F based on unbound concentration in plasma(3 hours post-dose)
- Unbound fraction and Vz/F based on unbound concentration in plasma(3 hours post-dose)
- 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)
- Unbound fraction and AUClast based on unbound concentration in plasma(3 hours post-dose)
- Unbound fraction and AUCinf based on unbound concentration in plasma(3 hours post-dose)
- Unbound fraction and Cmax based on unbound concentration in plasma(3 hours post-dose)
- Unbound fraction and Tmax based on unbound concentration in plasma(3 hours post-dose)