Evaluation of Hepatic Function Impairment on the Pharmacokinetics of LEE011

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.

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.

Study Overview

• Status: Completed
• Conditions: Normal Hepatic Function; Impaired Hepatic Function
• Intervention / Treatment: Drug: LEE011

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
  • Florida
    • Coral Gables, Florida, United States, 33124
      • University of Miami
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	PK profile includes the following parameters Tmax, Cmax, AUClast, AUCinf, T1/2, CL/F, Vz/F.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse events (AEs)	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.	From consent to 28 days post-dose

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Samant TS, Yang S, Miller M, Ji Y. Pharmacokinetics of Ribociclib in Subjects With Hepatic Impairment. J Clin Pharmacol. 2021 Aug;61(8):1001-1009. doi: 10.1002/jcph.1825. Epub 2021 Mar 12.

Helpful Links

• Results for CLEE011A2109 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2015
• Primary Completion (Actual): January 9, 2017
• Study Completion (Actual): January 9, 2017

Study Registration Dates

• First Submitted: March 2, 2015
• First Submitted That Met QC Criteria: March 9, 2015
• First Posted (Estimate): March 17, 2015

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: CLEE011A2109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No