Clinical trial NCT02388620: Evaluation of Hepatic Function Impairment on the Pharmacokinetics of LEE011
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Normal Hepatic Function
Impaired Hepatic Function
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-03-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 14 days
Secondary outcomes:
measure: Frequency of adverse events (AEs)
timeFrame: From consent to 28 days post-dose
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials
state: California
city: Coral Gables
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Samant TS, Yang S, Miller M, Ji Y. Pharmacokinetics of Ribociclib in Subjects With Hepatic Impairment. J Clin Pharmacol. 2021 Aug;61(8):1001-1009. doi: 10.1002/jcph.1825. Epub 2021 Mar 12.