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

Hepatic Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02474537
• Other study ID #: CINC280A2106
• Status: Completed
• Phase: Phase 1
• Start date: June 12, 2015
• Est. completion date: September 12, 2017

Study information

• Verified date: March 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: September 12, 2017
• Est. primary completion date: August 14, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria (all groups):

• Female subjects must be postmenopausal or sterile

• Good health, as determined by absence of clinically significant findings in medical history, physical examination, vital signs, and ECGs, unless it is consistent with known clinical disease for hepatic impairment subjects

• Adequate organ function and normal laboratory tests, unless it is consistent with known clinical disease for hepatic impairment subjects

• Body Mass Index (BMI) of 18- 36 kg/m2, with body weight = 50 kg

Inclusion Criteria (hepatic impairment groups):

• Confirmed liver disease

• Stable comorbidities are allowed as long as generally considered healthy

• Subjects with hepatic impairment must meet the following laboratory values:

• Aspartate transaminase (AST) = 5 x ULN

• Alanine transaminase (ALT) = 5 x ULN

• Total bilirubin = 3 x ULN (= 5 x XULN for subjects with severe hepatic impairment [group 4])

• Calculated creatinine clearance (using Cockcroft-Gault formula) = 45 mL/min

• Platelets > 50 x 10^9/L. Subjects with severe hepatic impairment can be enrolled if platelet count > 40 x 10^9/L

Exclusion Criteria (all groups):

• History or presence of clinically significant ECG abnormalities or clinically significant cardiovascular disease

• Immunocompromised subjects, including HIV

• Use of drugs known to affect CYP3A4

• Use of QT-prolonging drugs

• Use of any other drugs, unless they are required to treat the hepatic impairment subject's disease

• Use of proton pump inhibitors (PPI) medications within 7 days prior to dosing and during the current study until last day of confinement

Exclusion Criteria (normal hepatic function group):

• A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result

Exclusion Criteria (hepatic impairment groups):

• Active Grade 3 or 4 hepatic encephalopathy within 4 weeks of study entry

• Clinical evidence of severe ascites

• Ascites requiring paracentesis within 3 weeks prior to dosing

Other protocol-defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• INC280
Single 200 mg dose INC280

Locations

Country	Name	City	State
United States	Duke University Medical Center Oncology	Durham	North Carolina
United States	Clinical Pharmacology of Miami, LLC.	Miami	Florida
United States	University of Miami Miller School of Medicine Clinical Resea Oncology	Miami	Florida
United States	DaVita Clinical Research	Minneapolis	Minnesota
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUClast of INC280	INC280 pharmacokinetic parameters	Up to 72 hours post-dose
Primary	AUCinf of INC280	INC280 pharmacokinetic parameters	Up to 72 hours post-dose
Primary	Cmax of INC280	INC280 pharmacokinetic parameters	Up to 72 hours post-dose
Primary	Tmax of INC280	INC280 pharmacokinetic parameters	Up to 72 hours post-dose
Primary	T1/2 of INC280	INC280 pharmacokinetic parameters	Up to 72 hours post-dose
Primary	CL/F of INC280	INC280 pharmacokinetic parameters	Up to 72 hours post-dose
Primary	Vz/F of INC280	INC280 pharmacokinetic parameters	Up to 72 hours post-dose
Secondary	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
Secondary	Unbound fraction and AUClast based on unbound concentration in plasma	To assess the plasma protein binding of INC280	3 hours post-dose
Secondary	Unbound fraction and AUCinf based on unbound concentration in plasma	To assess the plasma protein binding of INC280	3 hours post-dose
Secondary	Unbound fraction and Cmax based on unbound concentration in plasma	To assess the plasma protein binding of INC280	3 hours post-dose
Secondary	Unbound fraction and Tmax based on unbound concentration in plasma	To assess the plasma protein binding of INC280	3 hours post-dose
Secondary	Unbound fraction and T1/2 based on unbound concentration in plasma	To assess the plasma protein binding of INC280	3 hours post-dose
Secondary	Unbound fraction and CL/F based on unbound concentration in plasma	To assess the plasma protein binding of INC280	3 hours post-dose
Secondary	Unbound fraction and Vz/F based on unbound concentration in plasma	To assess the plasma protein binding of INC280	3 hours post-dose

External Links

•   Results for CINC280A2106 can be found on the Novartis Clinical Trial Results website