Evaluation of Hepatic Function Impairment on the Pharmacokinetics of LEE011
- Registration Number
- NCT02388620
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
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).
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Severe Hepatic Impairment LEE011 Child-Pugh Classification C (score 10-15) Mild Hepatic Impairment LEE011 Child-Pugh Classification A (score 5-6) Moderate Hepatic Impairment LEE011 Child-Pugh Classification B (score 7-9) Normal Hepatic Function LEE011 Normal hepatic function; matched demography to hepatic impairment cohorts
- Primary Outcome Measures
Name Time Method 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. 14 days PK profile includes the following parameters Tmax, Cmax, AUClast, AUCinf, T1/2, CL/F, Vz/F.
- Secondary Outcome Measures
Name Time Method Frequency of adverse events (AEs) From consent to 28 days post-dose 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.
Trial Locations
- Locations (3)
Anaheim Clinical Trials
🇺🇸Anaheim, California, United States
Orlando Clinical Research Center
🇺🇸Orlando, Florida, United States
University of Miami
🇺🇸Coral Gables, Florida, United States