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Evaluation of Hepatic Function Impairment on the Pharmacokinetics of LEE011

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02388620
Collaborator
(none)
30
Enrollment
3
Locations
4
Arms
21.6
Actual Duration (Months)
10
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics (PK), safety and tolerability of a single oral dose of LEE011 in subjects with varying degrees of impaired hepatic function (based on Child-Pugh classification) as compared to demographically-matched control subjects with normal hepatic function.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
30 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I, Open Label, Multi-center, Parallel Cohort, Single Dose Study to Evaluate the Pharmacokinetics of LEE011 in Healthy Subjects With Normal Hepatic Function and Subjects With Impaired Hepatic Function.
Actual Study Start Date :
Mar 25, 2015
Actual Primary Completion Date :
Jan 9, 2017
Actual Study Completion Date :
Jan 9, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Normal Hepatic Function

Normal hepatic function; matched demography to hepatic impairment cohorts

Drug: LEE011
400 mg
Other Names:
  • Ribociclib

    		•
    Experimental: Mild Hepatic Impairment

    Child-Pugh Classification A (score 5-6)

    Drug: LEE011
    400 mg
    Other Names:
  • Ribociclib

    		•
    Experimental: Moderate Hepatic Impairment

    Child-Pugh Classification B (score 7-9)

    Drug: LEE011
    400 mg
    Other Names:
  • Ribociclib

    		•
    Experimental: Severe Hepatic Impairment

    Child-Pugh Classification C (score 10-15)

    Drug: LEE011
    400 mg
    Other Names:
  • Ribociclib

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Composite Pharmacokinetic (PK) profile of a single oral dose of LEE011 in subjects with impaired hepatic function as compared to healthy subjects with normal hepatic function. [14 days]

      PK profile includes the following parameters Tmax, Cmax, AUClast, AUCinf, T1/2, CL/F, Vz/F.

    Secondary Outcome Measures

    1. Frequency of adverse events (AEs) [From consent to 28 days post-dose]

      Safety profile of a single dose of LEE011 in healthy subjects and subjects with varying degrees of hepatic function includes changes observed in physical examination, changes in vital signs, changes in electrocardiograms (ECGs), abnormal laboratory results.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    All Subjects:

    Male or female (sterile or postmenopausal) subjects between 18-75 (both inclusive) years of age and healthy as determined by absence of clinically significant deviation from normal in medical history, physical examination, vital signs, electrocardiograms, and clinical laboratory determinations.

    Subjects must have a BMI between 18 kg/m2 and 36 kg/m2 and weight at least 50 kg and no more than 120 kg.

    Other than hepatic impairment, subjects must be in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, (except for additional inclusion criteria described below).

    Subjects in Child-Pugh A, B and C cohorts: Additional inclusion criteria

    Child-Pugh Clinical Assessment Score consistent with degree of hepatic impairment

    No change in hepatic status at least one month prior to dosing (i.e. worsening of Child-Pugh score).

    Exclusion Criteria:
    All Subjects:

    Subject has received a liver transplant at any time in the past and is on immunosuppressant therapy.

    History or presence of impaired cardiac function

    Any surgical or medical condition that may significantly alter the absorption, distribution, metabolism or excretion of drugs

    Administration of CYP3A4/5 inhibitors or inducers or CYP3A4 substrates with narrow therapeutic windows

    Administration of medications that prolong the QT interval

    History of immunodeficiency diseases, including HIV, as confirmed by (HIV-1, HIV-2) test.

    Participation in another clinical trial within 4 weeks prior to the study drug administration.

    Subjects with normal hepatic function:

    Additional exclusion criteria A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.

    Subjects in Child-Pugh A, B and C cohorts:

    Additional exclusion criteria

    Clinical evidence of severe ascites (e.g. requiring regular tapping).

    Bilirubin > 6 mg/dL

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Anaheim Clinical Trials Anaheim California United States 92801
    2 University of Miami Coral Gables Florida United States 33124
    3 Orlando Clinical Research Center Orlando Florida United States 32809

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02388620
    Other Study ID Numbers:
    • CLEE011A2109
    First Posted:
    Mar 17, 2015
    Last Update Posted:
    Dec 19, 2020
    Last Verified:
    Dec 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No

    Study Results

    No Results Posted as of Dec 19, 2020