Pharmacokinetic Study of BKM120 in Subjects With Hepatic Impairment

Hepatic Impairment Clinical Trial

Official title:

A Phase I, Multicenter, Open-label, Single-dose, Parallel Group Study to Assess the Pharmacokinetics of BKM120 in Subjects With Mild, Moderate and Severe Hepatic Impairmen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01727128
• Other study ID #: CBKM120C2104
• Secondary ID: 2011-002311-28
• Status: Completed
• Phase: Phase 1
• Start date: October 2011
• Est. completion date: August 2013

Study information

• Verified date: April 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Subjects should be in good health (except for additional/ specific inclusion criteria related to hepatic impaired subjects) as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests of no significance at screening

• 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

---Additional inclusion criteria Group 1 - control healthy subjects

• Subjects should be matched to the hepatic impaired subjects of group 2 in gender, age (± 10 years), weight (± 20%), and BMI (±5%)

---Additional inclusion criteria Group 2 - hepatic impaired subjects

• 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

Exclusion Criteria:

• 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

• Additional exclusion criteria Group 1 (matched healthy control subjects) History or presence of liver disease or liver injury as indicated by an abnormal liver function profile A positive Hepatitis C test or a positive Hepatitis B surface antigen (HBsAg)

• Additional exclusion criteria Group 2- hepatic impaired subjects

• 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

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• BKM120

Locations

Country	Name	City	State
Bulgaria	Novartis Investigative Site	Sofia
Germany	Novartis Investigative Site	Berlin
Russian Federation	Novartis Investigative Site	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Bulgaria,  Germany,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Adverse events severity	Severtiy of adverse events severity based on the CTCAE criteria to assess safety and tolerability of a single dose of BKM120	From baseline day-1 to 30 days post dose
Secondary	Change from baseline in laboratory parameters	Change from baseline in hematological and biochemical laboratory parameters	From baseline day-1 to 30 days post dose
Secondary	Change from baseline in ECG parameters	Change from baseline in ECG parameters	From baseline day-1 to 30 days post dose
Secondary	Change from baseline between PK parameters and total bilirubin, prothrombin time or INR and serum albumin	Relationship between PK parameters and baseline hepatic function parameters	From baseline day-1 to 15 days post dose
Secondary	measurement of plasma binding	Determination of the free fraction of BKM120 in plasmaexpressed weher relevant in terms of unbound drug concentration	From baseline day-1 to 15 days post dose
Secondary	Adverse events frequency	Frequency of adverse events severity based on the CTCAE criteria to assess safety and tolerability of a single dose of BKM120	From baseline day-1 to 30 days post dose

External Links

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