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

NCT ID: NCT02474537

Last Updated: 2020-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-12
• Study Completion Date: 2017-09-12

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.

Conditions

Hepatic Impairment

Keywords

hepatic impairment,; INC280,; Oral cMET Inhibitor,; Non-Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Normal hepatic function

Subjects with normal hepatic function

Group Type: EXPERIMENTAL

INC280

Intervention Type: DRUG

Single 200 mg dose INC280

Mild hepatic impairment

Subjects with mild hepatic impairment

Group Type: EXPERIMENTAL

INC280

Intervention Type: DRUG

Single 200 mg dose INC280

Moderate hepatic impairment

Subjects with moderate hepatic impairment

Group Type: EXPERIMENTAL

INC280

Intervention Type: DRUG

Single 200 mg dose INC280

Severe hepatic impairment

Subjects with severe hepatic impairment

Group Type: EXPERIMENTAL

INC280

Intervention Type: DRUG

Single 200 mg dose INC280

Interventions

INC280

Single 200 mg dose INC280

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• 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

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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

NovartisPharmaceuticals

Role: STUDY_DIRECTOR

NovartisPharmaceuticals

Locations

University of Miami Miller School of Medicine Clinical Resea Oncology

Miami, Florida, United States

Clinical Pharmacology of Miami, LLC.

Miami, Florida, United States

Orlando Clinical Research Center

Orlando, Florida, United States

DaVita Clinical Research

Minneapolis, Minnesota, United States

Duke University Medical Center Oncology

Durham, North Carolina, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34046915 (View on PubMed)

Related Links

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17140

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

Other Identifiers

CINC280A2106

Identifier Type: -

Identifier Source: org_study_id