<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01727128</url>
  </required_header>
  <id_info>
    <org_study_id>CBKM120C2104</org_study_id>
    <secondary_id>2011-002311-28</secondary_id>
    <nct_id>NCT01727128</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Study of BKM120 in Subjects With Hepatic Impairment</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To assess pharamcokinetics, safety and tolerability of a single oral dose of BKM120 in&#xD;
      subjects with mild, moderate and severe hepatic impairment&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2011</start_date>
  <completion_date type="Actual">August 2013</completion_date>
  <primary_completion_date type="Actual">August 2013</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma concentration of pharmacokinctis (PK) parameter Tmax</measure>
    <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</time_frame>
    <description>Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter TMax (time to maximum concentration)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma concentration of PK parameter Cmax</measure>
    <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</time_frame>
    <description>Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CMax (maximum concentration)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma concentration of PK parameter AUC-t</measure>
    <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</time_frame>
    <description>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</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma concentration of PK parameter AUC-last</measure>
    <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</time_frame>
    <description>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</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma concentration of PK parameter AUC-inf</measure>
    <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</time_frame>
    <description>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)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma concentration of PK parameter CL/F</measure>
    <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</time_frame>
    <description>infMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CL/F (clearance)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma concentration of PK parameter Vz/F</measure>
    <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</time_frame>
    <description>FMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter Vz/F (Volume distribution)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma concentration of PK parameter terminal T 1/2</measure>
    <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</time_frame>
    <description>Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter terminal T 1/2 (terminal half-life)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events severity</measure>
    <time_frame>From baseline day-1 to 30 days post dose</time_frame>
    <description>Severtiy of adverse events severity based on the CTCAE criteria to assess safety and tolerability of a single dose of BKM120</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in laboratory parameters</measure>
    <time_frame>From baseline day-1 to 30 days post dose</time_frame>
    <description>Change from baseline in hematological and biochemical laboratory parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in ECG parameters</measure>
    <time_frame>From baseline day-1 to 30 days post dose</time_frame>
    <description>Change from baseline in ECG parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline between PK parameters and total bilirubin, prothrombin time or INR and serum albumin</measure>
    <time_frame>From baseline day-1 to 15 days post dose</time_frame>
    <description>Relationship between PK parameters and baseline hepatic function parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>measurement of plasma binding</measure>
    <time_frame>From baseline day-1 to 15 days post dose</time_frame>
    <description>Determination of the free fraction of BKM120 in plasmaexpressed weher relevant in terms of unbound drug concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events frequency</measure>
    <time_frame>From baseline day-1 to 30 days post dose</time_frame>
    <description>Frequency of adverse events severity based on the CTCAE criteria to assess safety and tolerability of a single dose of BKM120</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Hepatic Impairment</condition>
  <arm_group>
    <arm_group_label>Mild Hepatic Impaired Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - mildly hepatically impaired</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moderate Hepatic Impaired group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - moderately hepatically impaired</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Severe Hepatic Impaired Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - Severely hepatically impaired</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Matching healthy control subjects who do not have hepatic impairment and are matched to the hepatic impaired subjects by sex, age, gender and BMI</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BKM120</intervention_name>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Mild Hepatic Impaired Group</arm_group_label>
    <arm_group_label>Moderate Hepatic Impaired group</arm_group_label>
    <arm_group_label>Severe Hepatic Impaired Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects should be in good health (except for additional/ specific inclusion criteria&#xD;
             related to hepatic impaired subjects) as determined by past medical history, physical&#xD;
             examination, vital signs, electrocardiogram, and laboratory tests of no significance&#xD;
             at screening&#xD;
&#xD;
          -  Subjects must weigh at least 45 kg to participate in this study, and must have a body&#xD;
             mass index (BMI) from (18.5-35.0 kg/m2)&#xD;
&#xD;
          -  Subjects must be able to communicate well with the investigator, to understand the&#xD;
             requirements of the study and agree to use strict contraception for 16 weeks after the&#xD;
             last BKM120 dose&#xD;
&#xD;
             ---Additional inclusion criteria Group 1 - control healthy subjects&#xD;
&#xD;
          -  Subjects should be matched to the hepatic impaired subjects of group 2 in gender, age&#xD;
             (± 10 years), weight (± 20%), and BMI (±5%)&#xD;
&#xD;
             ---Additional inclusion criteria Group 2 - hepatic impaired subjects&#xD;
&#xD;
          -  Subjects with physical signs consistent with stable hepatic impairment&#xD;
&#xD;
          -  Child-Pugh Clinical Assessment Score consistent with degree of hepatic impairment&#xD;
             (mild , moderate or severe)&#xD;
&#xD;
          -  Subjects must be free of significant medical disorders unrelated to the subject's&#xD;
             hepatic disorder as judged by the investigator.&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L&#xD;
&#xD;
          -  Platelet count ≥ 50 x 109 /L&#xD;
&#xD;
          -  serum creatinine ≤ 1.5 x ULN&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant illness, including infections, or hospitalization within the 2 weeks prior&#xD;
             to dosing, except for the hepatic impaired subjects who due to their liver disease may&#xD;
             be affected by significant medical problems which require frequent hospitalizations.&#xD;
             Invasive systemic fungal infections need to be fully resolved prior to study entry&#xD;
&#xD;
          -  Use of tobacco products within 2 weeks prior to dosing or during the study.&#xD;
&#xD;
          -  Consumption of alcohol within 2 days prior to dosing or during the study&#xD;
&#xD;
          -  Subjects with known ongoing alcohol and or/drug abuse within 1 month prior to dosing,&#xD;
             or evidence of such abuse as indicated by the laboratory assays conducted during&#xD;
             screening and/or at baseline&#xD;
&#xD;
          -  Subjects not willing to avoid certain study prohibited food, drink, over the counter&#xD;
             medicines and supplements&#xD;
&#xD;
          -  Any surgical or medical condition which might significantly alter the absorption,&#xD;
             distribution, metabolism, or excretion of drugs, or which may jeopardize the subject&#xD;
             in case of participation in the study.&#xD;
&#xD;
          -  Medical history of cardiac disease and/or clinically significant ECG abnormalities.&#xD;
&#xD;
          -  History of clinically significant hematologic, renal, endocrinologic, pulmonary&#xD;
             cardiovascular, hepatic, or allergic disease medically documented&#xD;
&#xD;
          -  Medical history of relevant psychiatric disorders&#xD;
&#xD;
          -  Subjects with Diabetes Mellitus or subjects with glucose levels out of normal range as&#xD;
             judge by the investigator&#xD;
&#xD;
          -  History of immunodeficiency diseases, including Human Immunodeficiency Virus (HIV), as&#xD;
             confirmed by (HIV-1, HIV-2) test&#xD;
&#xD;
               -  Additional exclusion criteria Group 1 (matched healthy control subjects) History&#xD;
                  or presence of liver disease or liver injury as indicated by an abnormal liver&#xD;
                  function profile A positive Hepatitis C test or a positive Hepatitis B surface&#xD;
                  antigen (HBsAg)&#xD;
&#xD;
               -  Additional exclusion criteria Group 2- hepatic impaired subjects&#xD;
&#xD;
          -  Subjects with clinically significant abnormal findings, not consistent with clinical&#xD;
             disease, upon physical examination, ECG or laboratory evaluation&#xD;
&#xD;
          -  Any evidence of progressive liver disease (within the last 4 weeks prior to the&#xD;
             screening visit) as indicated by liver transaminases, alkaline phosphatase and GGT or&#xD;
             a ≥ 50% worsening of serum bilirubin or prothrombin time&#xD;
&#xD;
          -  Total bilirubin &gt; 6mg/dl&#xD;
&#xD;
          -  Subject has ascites requiring intervention&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sofia</city>
        <zip>1618</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>14050</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Moscow</city>
        <zip>117198</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Germany</country>
    <country>Russian Federation</country>
  </location_countries>
  <removed_countries>
    <country>South Africa</country>
  </removed_countries>
  <link>
    <url>https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=12183</url>
    <description>Results for CBKM120C2104 can be found on the Novartis Clinical Trial Results Website</description>
  </link>
  <verification_date>April 2014</verification_date>
  <study_first_submitted>November 12, 2012</study_first_submitted>
  <study_first_submitted_qc>November 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <last_update_submitted>December 6, 2020</last_update_submitted>
  <last_update_submitted_qc>December 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatic impairment</keyword>
  <keyword>Clinical pharmacology study</keyword>
  <keyword>Volunteer study</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01727128
org study id: CBKM120C2104
secondary id: 2011-002311-28
nct id: NCT01727128
lead sponsor: 
has dmc: No
To assess pharamcokinetics, safety and tolerability of a single oral dose of BKM120 in
      subjects with mild, moderate and severe hepatic impairment
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Plasma concentration of pharmacokinctis (PK) parameter Tmax
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
description: Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter TMax (time to maximum concentration)
measure: Plasma concentration of PK parameter Cmax
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
description: Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CMax (maximum concentration)
measure: Plasma concentration of PK parameter AUC-t
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
description: 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
measure: Plasma concentration of PK parameter AUC-last
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
description: 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
measure: Plasma concentration of PK parameter AUC-inf
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
description: 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)
measure: Plasma concentration of PK parameter CL/F
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
description: infMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CL/F (clearance)
measure: Plasma concentration of PK parameter Vz/F
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
description: FMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter Vz/F (Volume distribution)
measure: Plasma concentration of PK parameter terminal T 1/2
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
description: Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter terminal T 1/2 (terminal half-life)
measure: Adverse events severity
time frame: From baseline day-1 to 30 days post dose
description: Severtiy of adverse events severity based on the CTCAE criteria to assess safety and tolerability of a single dose of BKM120
measure: Change from baseline in laboratory parameters
time frame: From baseline day-1 to 30 days post dose
description: Change from baseline in hematological and biochemical laboratory parameters
measure: Change from baseline in ECG parameters
time frame: From baseline day-1 to 30 days post dose
description: Change from baseline in ECG parameters
measure: Change from baseline between PK parameters and total bilirubin, prothrombin time or INR and serum albumin
time frame: From baseline day-1 to 15 days post dose
description: Relationship between PK parameters and baseline hepatic function parameters
measure: measurement of plasma binding
time frame: From baseline day-1 to 15 days post dose
description: Determination of the free fraction of BKM120 in plasmaexpressed weher relevant in terms of unbound drug concentration
measure: Adverse events frequency
time frame: From baseline day-1 to 30 days post dose
description: Frequency of adverse events severity based on the CTCAE criteria to assess safety and tolerability of a single dose of BKM120
arm group label: Mild Hepatic Impaired Group
arm group type: Experimental
description: Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - mildly hepatically impaired
arm group label: Moderate Hepatic Impaired group
arm group type: Experimental
description: Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - moderately hepatically impaired
arm group label: Severe Hepatic Impaired Group
arm group type: Experimental
description: Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - Severely hepatically impaired
arm group label: Control Group
arm group type: Experimental
description: Matching healthy control subjects who do not have hepatic impairment and are matched to the hepatic impaired subjects by sex, age, gender and BMI
intervention type: Drug
intervention name: BKM120
arm group label: Control Group
arm group label: Mild Hepatic Impaired Group
arm group label: Moderate Hepatic Impaired group
arm group label: Severe Hepatic Impaired Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
facility: 
country: Bulgaria
country: Germany
country: Russian Federation
country: South Africa
url: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=12183
description: Results for CBKM120C2104 can be found on the Novartis Clinical Trial Results Website
responsible party type: Sponsor
mesh term: Liver Diseases