Evaluation of Hepatic Function Impairment on the Pharmacokinetics of LEE011

NCT ID: NCT02388620

Last Updated: 2020-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-25

Study Completion Date

2017-01-09

Brief Summary

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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.

Detailed Description

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Conditions

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Normal Hepatic Function Impaired Hepatic Function

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Normal Hepatic Function

Normal hepatic function; matched demography to hepatic impairment cohorts

Group Type EXPERIMENTAL

LEE011

Intervention Type DRUG

400 mg

Mild Hepatic Impairment

Child-Pugh Classification A (score 5-6)

Group Type EXPERIMENTAL

LEE011

Intervention Type DRUG

400 mg

Moderate Hepatic Impairment

Child-Pugh Classification B (score 7-9)

Group Type EXPERIMENTAL

LEE011

Intervention Type DRUG

400 mg

Severe Hepatic Impairment

Child-Pugh Classification C (score 10-15)

Group Type EXPERIMENTAL

LEE011

Intervention Type DRUG

400 mg

Interventions

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LEE011

400 mg

Intervention Type DRUG

Other Intervention Names

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Ribociclib

Eligibility Criteria

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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.



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:


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


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

Bilirubin \> 6 mg/dL
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Anaheim Clinical Trials

Anaheim, California, United States

Site Status

University of Miami

Coral Gables, Florida, United States

Site Status

Orlando Clinical Research Center

Orlando, Florida, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 33555033 (View on PubMed)

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=16928

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

Other Identifiers

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CLEE011A2109

Identifier Type: -

Identifier Source: org_study_id