Pharmacokinetic Study of BKM120 in Subjects With Hepatic Impairment

NCT01727128 | Completed Phase 1

• 2 other identifiers: CBKM120C21042011-002311-28
• Study Type: interventional
• Target: 31
• Locations: 3 countries
• Sites: 3

Brief Summary

To assess pharamcokinetics, safety and tolerability of a single oral dose of BKM120 in subjects with mild, moderate and severe hepatic impairment

Conditions

Hepatic Impairment

Keywords

Hepatic impairment; Clinical pharmacology study; Volunteer study

Outcome Measures

Primary Outcomes (8)

• Plasma concentration of pharmacokinctis (PK) parameter Tmax

  Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter TMax (time to maximum concentration)

  predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose

• Plasma concentration of PK parameter Cmax

  Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CMax (maximum concentration)

  predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose

• Plasma concentration of PK parameter AUC-t

  Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-t (Area under the curve at specified timepoint) The specific key measure(s) or observation(s) that will be used to determine the effect of the intervention(s). Example: Change in left ventricular end systolic volume (LVESD) as measured by echocardiography Time to tumor progression Overall tumor response

  predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose

• Plasma concentration of PK parameter AUC-last

  Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-last (Area under the curve at last timepoint) The specific key measure(s) or observation(s) that will be used to determine the effect of the intervention(s). Example: Change in left ventricular end systolic volume (LVESD) as measured by echocardiography Time to tumor progression Overall tumor response

  predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose

• Plasma concentration of PK parameter AUC-inf

  Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-inf (Area under the curve to time infinity)

  predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose

• Plasma concentration of PK parameter CL/F

  infMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CL/F (clearance)

  predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose

• Plasma concentration of PK parameter Vz/F

  FMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter Vz/F (Volume distribution)

  predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose

• Plasma concentration of PK parameter terminal T 1/2

  Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter terminal T 1/2 (terminal half-life)

  predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose

Secondary Outcomes (6)

• Adverse events severity

  From baseline day-1 to 30 days post dose

• Change from baseline in laboratory parameters

  From baseline day-1 to 30 days post dose

• Change from baseline in ECG parameters

  From baseline day-1 to 30 days post dose

• Change from baseline between PK parameters and total bilirubin, prothrombin time or INR and serum albumin

  From baseline day-1 to 15 days post dose

• measurement of plasma binding

  From baseline day-1 to 15 days post dose

Study Arms (4)

Mild Hepatic Impaired Group

EXPERIMENTAL

Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - mildly hepatically impaired

Drug: BKM120

Moderate Hepatic Impaired group

EXPERIMENTAL

Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - moderately hepatically impaired

Drug: BKM120

Severe Hepatic Impaired Group

EXPERIMENTAL

Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - Severely hepatically impaired

Drug: BKM120

Control Group

EXPERIMENTAL

Matching healthy control subjects who do not have hepatic impairment and are matched to the hepatic impaired subjects by sex, age, gender and BMI

Drug: BKM120

Interventions

BKM120 DRUG

Control Group; Mild Hepatic Impaired Group; Moderate Hepatic Impaired group; Severe Hepatic Impaired 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:

• Subjects must weigh at least 45 kg to participate in this study, and must have a body mass index (BMI) from (18.5-35.0 kg/m2)
• Subjects must be able to communicate well with the investigator, to understand the requirements of the study and agree to use strict contraception for 16 weeks after the last BKM120 dose
• Subjects should be matched to the hepatic impaired subjects of group 2 in gender, age (± 10 years), weight (± 20%), and BMI (±5%)
• Subjects with physical signs consistent with stable hepatic impairment
• Child-Pugh Clinical Assessment Score consistent with degree of hepatic impairment (mild , moderate or severe)
• Subjects must be free of significant medical disorders unrelated to the subject's hepatic disorder as judged by the investigator.
• Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L
• Platelet count ≥ 50 x 109 /L
• serum creatinine ≤ 1.5 x ULN

You may not qualify if:

• Significant illness, including infections, or hospitalization within the 2 weeks prior to dosing, except for the hepatic impaired subjects who due to their liver disease may be affected by significant medical problems which require frequent hospitalizations. Invasive systemic fungal infections need to be fully resolved prior to study entry
• Use of tobacco products within 2 weeks prior to dosing or during the study.
• Consumption of alcohol within 2 days prior to dosing or during the study
• Subjects with known ongoing alcohol and or/drug abuse within 1 month prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and/or at baseline
• Subjects not willing to avoid certain study prohibited food, drink, over the counter medicines and supplements
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
• Medical history of cardiac disease and/or clinically significant ECG abnormalities.
• History of clinically significant hematologic, renal, endocrinologic, pulmonary cardiovascular, hepatic, or allergic disease medically documented
• Medical history of relevant psychiatric disorders
• Subjects with Diabetes Mellitus or subjects with glucose levels out of normal range as judge by the investigator
• History of immunodeficiency diseases, including Human Immunodeficiency Virus (HIV), as confirmed by (HIV-1, HIV-2) test
• Subjects with clinically significant abnormal findings, not consistent with clinical disease, upon physical examination, ECG or laboratory evaluation
• Any evidence of progressive liver disease (within the last 4 weeks prior to the screening visit) as indicated by liver transaminases, alkaline phosphatase and GGT or a ≥ 50% worsening of serum bilirubin or prothrombin time
• Total bilirubin \> 6mg/dl
• Subject has ascites requiring intervention

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Novartis Investigative Site

Sofia, 1618, Bulgaria

Location

Novartis Investigative Site

Berlin, 14050, Germany

Location

Novartis Investigative Site

Moscow, 117198, Russia

Location

Related Links

• Results for CBKM120C2104 can be found on the Novartis Clinical Trial Results Website

MeSH Terms

Interventions

NVP-BKM120

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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2012
• First Posted: November 15, 2012
• Study Start: October 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: December 9, 2020

Record last verified: 2014-04

Locations

BU (1); DE (1); RU (1)