Skip to main content
OpenTrials
Completed

NCT Number: NCT02624557

Pharmacokinetic Study of Alpelisib in Subjects With Hepatic Impairment.

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

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Hepatic Impairment

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

DaVita Clinical Research-Denver, Lakewood, Colorado, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Alpelisib

Drug

Subjects will receive a single dose of 300 mg alpelisib.

Primary outcomes

  1. Plasma pharmacokinetic (PK) parameter Cmax

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

    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.

  2. PK parameter AUClast

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

    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.

  3. PK parameter AUCinf

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

    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.

Secondary outcomes

  1. PK parameter AUC0-t

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

    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.

  2. PK parameter tmax

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

    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.

  3. PK parameter Cl/F

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

    Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter Cl/F (apparent oral total drug total plasma clearance calculated from steady-state exposure data ). Cl/F determined from the plasma concentration-time profile using non-compartmental analysis.

  4. PK parameter Vz/F

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

    Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter Vz/F (the apparent volume of distribution during terminal phase). Vz/F determined from the plasma concentration-time profile using non-compartmental analysis.

  5. PK parameter T1/2

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

    Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter T1/2 (elimination half-life associated with the terminal slope (lambda-z) of a semi logarithmic concentration-time curve). T1/2 determined from the plasma concentration-time profile using non-compartmental analysis.

  6. Relationship between PK parameters Cmax, AUClast, AUCinf and hepatic function parameters

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

    Determination of the relationship between the primary PK parameters Cmax, AUClast, AUCinf and baseline hepatic function parameters total bilirubin, INR and serum albumin.

  7. Adverse events severity and frequency

    Time frame: Baseline Day 1 to 30 days post-dose

    Assessment of safety and tolerability of a single dose alpelisib in hepatic impaired subjects compared with healthy matching control subjects by assessing the frequency and severity of adverse events based on the CTCAE criteria.

  8. Change from baseline in laboratory parameters

    Time frame: Baseline Day 1 to 30 days post-dose

    Assessment of safety and tolerability of a single dose alpelisib in hepatic impaired subjects compared with healthy matching control subjects by assessing the change from baseline in hematological and biochemical laboratory parameters.

  9. Change from baseline in ECG parameters

    Time frame: Baseline Day 1 to 30 days post-dose

    Assessment of safety and tolerability of a single dose alpelisib in hepatic impaired subjects compared with healthy matching control subjects by assessing the change from baseline in ECG parameters.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Phase 1, Open-label, Single-dose, Multicenter, Parallel Group Study to Assess the Pharmacokinetics and Safety of Alpelisib (BYL719) in Subjects With Hepatic Impairment Compared to Matched Healthy Control Subjects.

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Dec 8, 2015
Registry last updated
Dec 9, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.