Clinical trial NCT02624557: Pharmacokinetic Study of Alpelisib in Subjects With Hepatic Impairment.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Hepatic impairment
Healthy volunteers
Clinical pharmacology study
BYL719
alpelisib
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-12-08
Enrollment: 23
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: BASIC_SCIENCE

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


Eligibility criteria: 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.

Primary outcomes:
measure: Plasma pharmacokinetic (PK) parameter Cmax
timeFrame: predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
measure: PK parameter AUClast
timeFrame: predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
measure: PK parameter AUCinf
timeFrame: predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
Secondary outcomes:
measure: PK parameter AUC0-t
timeFrame: predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
measure: PK parameter tmax
timeFrame: predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
measure: PK parameter Cl/F
timeFrame: predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
measure: PK parameter Vz/F
timeFrame: predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
measure: PK parameter T1/2
timeFrame: predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
measure: Relationship between PK parameters Cmax, AUClast, AUCinf and hepatic function parameters
timeFrame: predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
measure: Adverse events severity and frequency
timeFrame: Baseline Day 1 to 30 days post-dose
measure: Change from baseline in laboratory parameters
timeFrame: Baseline Day 1 to 30 days post-dose
measure: Change from baseline in ECG parameters
timeFrame: Baseline Day 1 to 30 days post-dose
Other outcomes:
Locations:
city: Lakewood
country: United States
facility: DaVita Clinical Research-Denver
state: Colorado
city: Miami
country: United States
facility: University of Miami / Clinical Research Services, Inc.
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Minneapolis
country: United States
facility: DaVita Clinical Research
state: Minnesota
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: