Pharmacokinetic Study of Alpelisib in Subjects With Hepatic Impairment.

NCT02624557 | Completed Phase 1 FDA Drug

• 1 other identifier: CBYL719A2105
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Hepatic Impairment

Keywords

Hepatic impairment; Healthy volunteers; Clinical pharmacology study; BYL719; alpelisib

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (9)

• PK parameter AUC0-t

  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

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

• PK parameter Cl/F

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

• PK parameter Vz/F

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

• PK parameter T1/2

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

Study Arms (3)

Moderate hepatic impairment group

EXPERIMENTAL

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

Drug: Alpelisib

Severe hepatic impairment group

EXPERIMENTAL

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

Drug: Alpelisib

Matching healthy control group

EXPERIMENTAL

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

Drug: Alpelisib

Interventions

Alpelisib DRUG

Subjects will receive a single dose of 300 mg alpelisib.

Matching healthy control group; Moderate hepatic impairment group; Severe hepatic impairment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (4)

DaVita Clinical Research-Denver

Lakewood, Colorado, 80228, United States

Location

University of Miami / Clinical Research Services, Inc.

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

DaVita Clinical Research

Minneapolis, Minnesota, 55404, United States

Location

Related Links

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

MeSH Terms

Interventions

Alpelisib

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2015
• First Posted: December 8, 2015
• Study Start: December 21, 2015
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: December 9, 2020

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)