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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normal hepatic function | Experimental | Subjects with normal hepatic function |
|
| Mild hepatic impairment | Experimental | Subjects with mild hepatic impairment |
|
| Moderate hepatic impairment | Experimental | Subjects with moderate hepatic impairment |
|
| Severe hepatic impairment | Experimental | Subjects with severe hepatic impairment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| INC280 | Drug | Single 200 mg dose INC280 |
|
| Measure | Description | Time Frame |
|---|---|---|
| AUClast of INC280 | INC280 pharmacokinetic parameters | Up to 72 hours post-dose |
| AUCinf of INC280 | INC280 pharmacokinetic parameters | Up to 72 hours post-dose |
| Cmax of INC280 | INC280 pharmacokinetic parameters | Up to 72 hours post-dose |
| Tmax of INC280 | INC280 pharmacokinetic parameters | Up to 72 hours post-dose |
| T1/2 of INC280 | INC280 pharmacokinetic parameters | Up to 72 hours post-dose |
| CL/F of INC280 | INC280 pharmacokinetic parameters | Up to 72 hours post-dose |
| Vz/F of INC280 | INC280 pharmacokinetic parameters | Up to 72 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events based on the CTCAE v4.03 grade (severity) and frequency, and other safety data (e.g., ECG, laboratory results) | Safety | Up to 30 days |
| Unbound fraction and AUClast based on unbound concentration in plasma |
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Inclusion Criteria (all groups):
Inclusion Criteria (hepatic impairment groups):
Exclusion Criteria (all groups):
Exclusion Criteria (normal hepatic function group):
Exclusion Criteria (hepatic impairment groups):
Other protocol-defined inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| NovartisPharmaceuticals | NovartisPharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Miami Miller School of Medicine Clinical Resea Oncology | Miami | Florida | 33136 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34046915 | Derived | Chen X, Cui X, Pognan N, Quinlan M, Kapoor S, Rahmanzadeh G, Giovannini M, Marbury TC. Pharmacokinetics of capmatinib in participants with hepatic impairment: A phase 1, open-label, single-dose, parallel-group study. Br J Clin Pharmacol. 2022 Jan;88(1):91-102. doi: 10.1111/bcp.14929. Epub 2021 Jun 18. |
| Label | URL |
|---|---|
| Results for CINC280A2106 can be found on the Novartis Clinical Trial Results website | View source |
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| ID | Term |
|---|---|
| C000613976 | capmatinib |
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To assess the plasma protein binding of INC280
| 3 hours post-dose |
| Unbound fraction and AUCinf based on unbound concentration in plasma | To assess the plasma protein binding of INC280 | 3 hours post-dose |
| Unbound fraction and Cmax based on unbound concentration in plasma | To assess the plasma protein binding of INC280 | 3 hours post-dose |
| Unbound fraction and Tmax based on unbound concentration in plasma | To assess the plasma protein binding of INC280 | 3 hours post-dose |
| Unbound fraction and T1/2 based on unbound concentration in plasma | To assess the plasma protein binding of INC280 | 3 hours post-dose |
| Unbound fraction and CL/F based on unbound concentration in plasma | To assess the plasma protein binding of INC280 | 3 hours post-dose |
| Unbound fraction and Vz/F based on unbound concentration in plasma | To assess the plasma protein binding of INC280 | 3 hours post-dose |
| Clinical Pharmacology of Miami, LLC. |
| Miami |
| Florida |
| 33142 |
| United States |
| Orlando Clinical Research Center | Orlando | Florida | 32086 | United States |
| DaVita Clinical Research | Minneapolis | Minnesota | 55404 | United States |
| Duke University Medical Center Oncology | Durham | North Carolina | 27710 | United States |