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

Status:	Completed
Conditions:	Gastrointestinal
Therapuetic Areas:	Gastroenterology
Healthy:	No
Age Range:	18 - 75
Updated:	3/29/2019
Start Date:	June 12, 2015
End Date:	September 12, 2017

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

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.

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.

We found this trial at

sites

Clinical Pharmacology of Miami

Miami, Florida 33014

Principal Investigator: Kenneth Lasseter

Phone: 305-817-2900

from

Miami, FL