To assess pharamcokinetics, safety and tolerability of a single oral dose of BKM120 in subjects with mild, moderate and severe hepatic impairment
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
31
Novartis Investigative Site
Sofia, Bulgaria
Novartis Investigative Site
Berlin, Germany
Novartis Investigative Site
Moscow, Russia
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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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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)
Time frame: 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)
Time frame: 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)
Time frame: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Adverse events severity
Severtiy of adverse events severity based on the CTCAE criteria to assess safety and tolerability of a single dose of BKM120
Time frame: From baseline day-1 to 30 days post dose
Change from baseline in laboratory parameters
Change from baseline in hematological and biochemical laboratory parameters
Time frame: From baseline day-1 to 30 days post dose
Change from baseline in ECG parameters
Change from baseline in ECG parameters
Time frame: 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
Relationship between PK parameters and baseline hepatic function parameters
Time frame: From baseline day-1 to 15 days post dose
measurement of plasma binding
Determination of the free fraction of BKM120 in plasmaexpressed weher relevant in terms of unbound drug concentration
Time frame: From baseline day-1 to 15 days post dose
Adverse events frequency
Frequency of adverse events severity based on the CTCAE criteria to assess safety and tolerability of a single dose of BKM120
Time frame: From baseline day-1 to 30 days post dose