Impaired Hepatic Function, Normal Hepatic Function
Conditions
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.
Interventions
DRUGLEE011
400 mg
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed