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.
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.
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.
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