Evaluation of Hepatic Function Impairment on the Pharmacokinetics of LEE011

NCT02388620 | Completed Phase 1 FDA Drug

• 1 other identifier: CLEE011A2109
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

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.

Conditions

Normal Hepatic Function; Impaired Hepatic Function

Outcome Measures

Primary Outcomes (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.

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

  14 days

Secondary Outcomes (1)

• Frequency of adverse events (AEs)

  From consent to 28 days post-dose

Study Arms (4)

Normal Hepatic Function

EXPERIMENTAL

Normal hepatic function; matched demography to hepatic impairment cohorts

Drug: LEE011

Mild Hepatic Impairment

EXPERIMENTAL

Child-Pugh Classification A (score 5-6)

Drug: LEE011

Moderate Hepatic Impairment

EXPERIMENTAL

Child-Pugh Classification B (score 7-9)

Drug: LEE011

Severe Hepatic Impairment

EXPERIMENTAL

Child-Pugh Classification C (score 10-15)

Drug: LEE011

Interventions

LEE011 DRUG

400 mg

Also known as: Ribociclib

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:

• 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.
• 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).

You may not qualify if:

• 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:
• Subjects in Child-Pugh A, B and C cohorts:
• Clinical evidence of severe ascites (e.g. requiring regular tapping).
• Bilirubin \> 6 mg/dL

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Anaheim Clinical Trials

Anaheim, California, 92801, United States

Location

University of Miami

Coral Gables, Florida, 33124, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Related Publications (1)

• 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.

  PMID: 33555033 DERIVED

Related Links

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

MeSH Terms

Interventions

ribociclib

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  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: March 2, 2015
• First Posted: March 17, 2015
• Study Start: March 25, 2015
• Primary Completion: January 9, 2017
• Study Completion: January 9, 2017
• Last Updated: December 19, 2020

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)