Evaluation of Hepatic Function Impairment on the Pharmacokinetics of LEE011

Impaired Hepatic Function Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02388620
• Other study ID #: CLEE011A2109
• Status: Completed
• Phase: Phase 1
• Start date: March 25, 2015
• Est. completion date: January 9, 2017

Study information

• Verified date: December 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 9, 2017
• Est. primary completion date: January 9, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Impaired Hepatic Function
• Normal Hepatic Function

Intervention

Drug:
• LEE011
400 mg

Locations

Country	Name	City	State
United States	Anaheim Clinical Trials	Anaheim	California
United States	University of Miami	Coral Gables	Florida
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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

External Links

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