Pharmacokinetic Study of Alpelisib in Subjects With Hepatic Impairment.

Hepatic Impairment Clinical Trial

Official 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02624557
• Other study ID #: CBYL719A2105
• Status: Completed
• Phase: Phase 1
• Start date: December 21, 2015
• Est. completion date: October 1, 2017

Study information

• Verified date: May 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: October 1, 2017
• Est. primary completion date: October 1, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Alpelisib
Subjects will receive a single dose of 300 mg alpelisib.

Locations

Country	Name	City	State
United States	DaVita Clinical Research-Denver	Lakewood	Colorado
United States	University of Miami / Clinical Research Services, Inc.	Miami	Florida
United States	DaVita Clinical Research	Minneapolis	Minnesota
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
Primary	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.	predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
Primary	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.	predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
Secondary	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.	predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
Secondary	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.	predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
Secondary	PK parameter Cl/F	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.	predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
Secondary	PK parameter Vz/F	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.	predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
Secondary	PK parameter T1/2	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.	predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
Secondary	Relationship between PK parameters Cmax, AUClast, AUCinf and hepatic function parameters	Determination of the relationship between the primary PK parameters Cmax, AUClast, AUCinf and baseline hepatic function parameters total bilirubin, INR and serum albumin.	predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
Secondary	Adverse events severity and frequency	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.	Baseline Day 1 to 30 days post-dose
Secondary	Change from baseline in laboratory parameters	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.	Baseline Day 1 to 30 days post-dose
Secondary	Change from baseline in ECG parameters	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.	Baseline Day 1 to 30 days post-dose

External Links

•   Results for CBYL719A2105 can be found on the Novartis Clinical Trial Results Website