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

Novartis

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment

Treatments: Drug: INC280

Study type: Interventional

Funder types: Industry

Identifiers

NCT02474537

CINC280A2106

Details and patient eligibility

About

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.

Enrollment: 31 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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31 participants in 4 patient groups

Normal hepatic function

Experimental group

Description:

Subjects with normal hepatic function

Treatment:

Drug: INC280

Mild hepatic impairment

Experimental group

Description:

Subjects with mild hepatic impairment

Treatment:

Drug: INC280

Moderate hepatic impairment

Experimental group

Description:

Subjects with moderate hepatic impairment

Treatment:

Drug: INC280

Severe hepatic impairment

Experimental group

Description:

Subjects with severe hepatic impairment

Treatment:

Drug: INC280