Evaluation of Hepatic Function Impairment on the Pharmacokinetics of LEE011

Novartis

Status and phase: Completed; Phase 1

Conditions: Impaired Hepatic Function; Normal Hepatic Function

Treatments: Drug: LEE011

Study type: Interventional

Funder types: Industry

Identifiers

NCT02388620

CLEE011A2109

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 4 patient groups

Normal Hepatic Function

Experimental group

Description:

Normal hepatic function; matched demography to hepatic impairment cohorts

Treatment:

Drug: LEE011

Mild Hepatic Impairment

Experimental group

Description:

Child-Pugh Classification A (score 5-6)

Treatment:

Drug: LEE011

Moderate Hepatic Impairment

Experimental group

Description:

Child-Pugh Classification B (score 7-9)

Treatment:

Drug: LEE011

Severe Hepatic Impairment

Experimental group

Description:

Child-Pugh Classification C (score 10-15)

Treatment:

Drug: LEE011