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

8. december 2020 opdateret af: Novartis Pharmaceuticals

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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

31

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Florida
      • Miami, Florida, Forenede Stater, 33136
        • University of Miami Miller School of Medicine Clinical Resea Oncology
      • Miami, Florida, Forenede Stater, 33142
        • Clinical Pharmacology of Miami, LLC.
      • Orlando, Florida, Forenede Stater, 32086
        • Orlando Clinical Research Center
    • Minnesota
      • Minneapolis, Minnesota, Forenede Stater, 55404
        • DaVita Clinical Research
    • North Carolina
      • Durham, North Carolina, Forenede Stater, 27710
        • Duke University Medical Center Oncology

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 75 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ja

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Normal leverfunktion
Personer med normal leverfunktion
Medicin: INC280
Single 200 mg dose INC280
Eksperimentel: Let nedsat leverfunktion
Personer med let nedsat leverfunktion
Medicin: INC280
Single 200 mg dose INC280
Eksperimentel: Moderat nedsat leverfunktion
Personer med moderat nedsat leverfunktion
Medicin: INC280
Single 200 mg dose INC280
Eksperimentel: Severe hepatic impairment
Subjects with severe hepatic impairment
Medicin: INC280
Single 200 mg dose INC280

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
AUClast of INC280
Tidsramme: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose
AUCinf of INC280
Tidsramme: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose
Cmax of INC280
Tidsramme: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose
Tmax of INC280
Tidsramme: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose
T1/2 of INC280
Tidsramme: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose
CL/F of INC280
Tidsramme: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose
Vz/F of INC280
Tidsramme: Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Adverse events based on the CTCAE v4.03 grade (severity) and frequency, and other safety data (e.g., ECG, laboratory results)
Tidsramme: Up to 30 days
Safety
Up to 30 days
Unbound fraction and AUClast based on unbound concentration in plasma
Tidsramme: 3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose
Unbound fraction and AUCinf based on unbound concentration in plasma
Tidsramme: 3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose
Unbound fraction and Cmax based on unbound concentration in plasma
Tidsramme: 3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose
Unbound fraction and Tmax based on unbound concentration in plasma
Tidsramme: 3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose
Unbound fraction and T1/2 based on unbound concentration in plasma
Tidsramme: 3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose
Unbound fraction and CL/F based on unbound concentration in plasma
Tidsramme: 3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose
Unbound fraction and Vz/F based on unbound concentration in plasma
Tidsramme: 3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Novartis Pharmaceuticals

Efterforskere

  • Studieleder: NovartisPharmaceuticals, NovartisPharmaceuticals

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

12. juni 2015

Primær færdiggørelse (Faktiske)

14. august 2017

Studieafslutning (Faktiske)

12. september 2017

Datoer for studieregistrering

Først indsendt

9. juni 2015

Først indsendt, der opfyldte QC-kriterier

16. juni 2015

Først opslået (Skøn)

17. juni 2015

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

10. december 2020

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

8. december 2020

Sidst verificeret

1. marts 2019

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CINC280A2106

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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Kliniske forsøg med Nedsat leverfunktion

Kliniske forsøg med INC280

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Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Pakistan

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner