Pharmacokinetic Study of Alpelisib in Subjects With Hepatic Impairment.

Novartis

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment

Treatments: Drug: Alpelisib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02624557

CBYL719A2105

Details and patient eligibility

About

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

Enrollment: 23 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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23 participants in 3 patient groups

Moderate hepatic impairment group

Experimental group

Description:

Subjects with moderate hepatic impairment with Child-Pugh score 7 - 9

Treatment:

Drug: Alpelisib

Severe hepatic impairment group

Experimental group

Description:

Subjects with severe hepatic impairment with Child-Pugh score 10 - 15

Treatment:

Drug: Alpelisib

Matching healthy control group

Experimental group

Description:

Subjects with apparent normal liver function matched to the hepatic impairment subjects by sex, race, age, and weight.

Treatment:

Drug: Alpelisib