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

NCT02474537 | Completed Phase 1 FDA Drug

• 1 other identifier: CINC280A2106
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (7)

• 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

Secondary Outcomes (8)

• Adverse events based on the CTCAE v4.03 grade (severity) and frequency, and other safety data (e.g., ECG, laboratory results)

  Up to 30 days

• Unbound fraction and AUClast based on unbound concentration in plasma

  3 hours post-dose

• Unbound fraction and AUCinf based on unbound concentration in plasma

  3 hours post-dose

• Unbound fraction and Cmax based on unbound concentration in plasma

  3 hours post-dose

• Unbound fraction and Tmax based on unbound concentration in plasma

  3 hours post-dose

Study Arms (4)

Normal hepatic function

EXPERIMENTAL

Subjects with normal hepatic function

Drug: INC280

Mild hepatic impairment

EXPERIMENTAL

Subjects with mild hepatic impairment

Drug: INC280

Moderate hepatic impairment

EXPERIMENTAL

Subjects with moderate hepatic impairment

Drug: INC280

Severe hepatic impairment

EXPERIMENTAL

Subjects with severe hepatic impairment

Drug: INC280

Interventions

INC280 DRUG

Single 200 mg dose INC280

Mild hepatic impairment; Moderate hepatic impairment; Normal hepatic function; Severe hepatic impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

University of Miami Miller School of Medicine Clinical Resea Oncology

Miami, Florida, 33136, United States

Location

Clinical Pharmacology of Miami, LLC.

Miami, Florida, 33142, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32086, United States

Location

DaVita Clinical Research

Minneapolis, Minnesota, 55404, United States

Location

Duke University Medical Center Oncology

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• 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.

  PMID: 34046915 DERIVED

Related Links

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

MeSH Terms

Interventions

capmatinib

Study Officials

• NovartisPharmaceuticals

  NovartisPharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2015
• First Posted: June 17, 2015
• Study Start: June 12, 2015
• Primary Completion: August 14, 2017
• Study Completion: September 12, 2017
• Last Updated: December 10, 2020

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)