Pharmacokinetic Study of Alpelisib in Subjects With Hepatic Impairment.

Novartis Pharmaceuticals23 enrolled

Overview

To characterize the pharmacokinetics and safety of alpelisib in subjects with hepatic impairment compared to matched healthy control subjects.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Hepatic Impairment

Interventions

AlpelisibDRUG

Subjects will receive a single dose of 300 mg alpelisib.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: -Other then hepatic impairment, subjects should be in good health as determined by past medical history, physical examination, vital signs, electrocardiogram (except for additional inclusion criteria for hepatic impaired subjects). -Subjects must weigh at least 50 kg and no more than 120 kg and have a body mass index in the range 18.0-36.0 kg/m2. Additional criteria for hepatic impaired subjects: -Subjects must have a score clinically determined and calculated as per the Child-Pugh classification and consistent with the degree of hepatic impairment in which study is currently enrolling. -Stable Child-Pugh status within 28 days prior to dosing. Exclusion Criteria: All subjects: * Subject has received a liver transplant at any time in the past and is on immunosuppressant therapy. * Smokers not willing to limit the use of tobacco to 10 cigarettes per day. -Surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject's safety in case of participation in the study. -Use of any herbal medications/supplements. History of acute pancreatitis within 1 year of study entry. Additional criteria for subjects with normal liver function: -Use of any prescription or non-prescription medication. -Positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. Additional criteria for hepatic impaired subjects: -Use of any prescription or non-prescription medication, that has the potential to interact with alpelisb. Concomitant medications without potential to interact with alpelisib must be stable in dose. -Encephalopathy grade 3 or worse. -Total bilirubin \> 6 mg/dl. Screening or baseline ECG: QTcF\>480msec for both genders Other protocol-defined inclusion/exclusion criteria may apply.

Locations (4)

DaVita Clinical Research-Denver

Lakewood, Colorado, United States

University of Miami / Clinical Research Services, Inc.

Miami, Florida, United States

Orlando Clinical Research Center

Orlando, Florida, United States

DaVita Clinical Research

Minneapolis, Minnesota, United States

Outcomes

Primary Outcomes

Plasma pharmacokinetic (PK) parameter Cmax

Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the maximum plasma concentration (PK parameter Cmax). Cmax directly determined from the plasma concentration-time profile.

Time frame: predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose

PK parameter AUClast

Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter AUClast (area under the concentration-time curve from time zero to the last measurable concentration sampling time). AUC determined from the plasma concentration-time profile using non-compartmental analysis.

Time frame: predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose

PK parameter AUCinf

Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter AUCinf (area under the concentration-time curve from time zero to infinity ). AUC determined from the plasma concentration-time profile using non-compartmental analysis.

Time frame: predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose

Secondary Outcomes

PK parameter AUC0-t

Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter AUC0-t (the partial area under the concentration-time curve from time zero to t hours post dose). AUC determined from the plasma concentration-time profile using non-compartmental analysis.

Time frame: predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose

PK parameter tmax

Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter tmax (time to reach maximum plasma concentration), directly determined from the plasma concentration-time profile.

Data from ClinicalTrials.gov

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