<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/NCT01686555</url>
  </required_header>
  <id_info>
    <org_study_id>M13-093</org_study_id>
    <secondary_id>2013-000328-33</secondary_id>
    <nct_id>NCT01686555</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ABT-199 in Female Patients With Systemic Lupus Erythematosus (SLE)</brief_title>
  <official_title>Assessment of the Safety, Tolerability, and Pharmacokinetics of ABT-199 After Single and Multiple Ascending Doses in Female Subjects With Systemic Lupus Erythematosus (SLE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AbbVie (prior sponsor, Abbott)</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AbbVie</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To assess the safety, tolerability and pharmacokinetics of ABT-199 in female subjects with&#xD;
      Systemic Lupus Erythematosus.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 1, randomized, double-blind, placebo-controlled, single-and multiple&#xD;
      ascending dose study. Up to eighty-eight subjects with Systemic Lupus Erythematosus will be&#xD;
      selected to participate. Subjects will be randomized to receive either ABT-199 or placebo.&#xD;
      Subjects will be administered ABT-199/placebo as a single dose or up to 14 days as multiple&#xD;
      doses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with Adverse Events</measure>
    <time_frame>From first dose of ABT-199 until 28 days after single dose of ABT-199 and until 21 days after the last multiple dose of ABT-199</time_frame>
    <description>Collect all adverse events at each visit</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physical Exam including vital signs</measure>
    <time_frame>Prior to the first dose of ABT-199 until 28 days after single dose of ABT-199 and until 21 days after the last multiple dose of ABT-199</time_frame>
    <description>Blood pressure, heart rate and body temperature</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical Lab Testing</measure>
    <time_frame>Prior to the first dose of ABT-199 until 28 days after single dose of ABT-199 and until 21 days after the last multiple dose of ABT-199</time_frame>
    <description>Hematology, Chemistry, and Urinalysis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Electrocardiogram (ECG) Measurements</measure>
    <time_frame>For 24 hours after a single dose of ABT-199 and up to 24 hours after the seventh dose of multiple doses of ABT-199</time_frame>
    <description>ECGs done in triplicate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum observed serum concentration (Cmax) of ABT-199</measure>
    <time_frame>For 72 hours after a single dose of ABT-199 and for 24 hours after the seventh dose of multiple doses of ABT-199</time_frame>
    <description>Cmax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Cmax (Tmax) of ABT-199</measure>
    <time_frame>For 72 hours after a single dose of ABT-199 and for 24 hours after the seventh dose of multiple doses of ABT-199</time_frame>
    <description>Time to Cmax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The area under the time curve (AUC) of ABT-199</measure>
    <time_frame>For 72 hours after a single dose of ABT-199 and for 24 hours after the seventh dose of multiple doses of ABT-199</time_frame>
    <description>the area under the exposure-time curve of ABT-199 extrapolated to infinite time for single doses and up to 24 hrs for multiple doses of ABT-199</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The terminal phase elimination rate constant and the terminal elimination half-life (t1/2) of ABT-199</measure>
    <time_frame>For 72 hours after a single dose of ABT-199</time_frame>
    <description>The terminal phase elimination rate constant and the terminal elimination half-life (t1/2) of ABT-199</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measurement of lymphocyte depletion and recovery</measure>
    <time_frame>Prior to the first dose of ABT-199 until 28 days after single dose of ABT-199 and until 21 days after the last multiple dose of ABT-199</time_frame>
    <description>explore pharmacokinetic/pharmacodynamic relationship</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">97</enrollment>
  <condition>Lupus Erythematosus</condition>
  <arm_group>
    <arm_group_label>Single Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects enrolled in the Single Ascending Dose (SAD) part of the study will receive a single dose of study drug or placebo. (Groups 1, 2, 3, 4, 5 and 6).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects enrolled in the Multiple Ascending Dose (MAD) part of the study will receive multiple doses of study drug or placebo. (Groups 7, 8, 9, 10 and 11)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ABT-199</intervention_name>
    <description>Tablet</description>
    <arm_group_label>Multiple Dose</arm_group_label>
    <arm_group_label>Single Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Tablet</description>
    <arm_group_label>Multiple Dose</arm_group_label>
    <arm_group_label>Single Dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of systemic lupus erythematosus for at least 6 months.&#xD;
&#xD;
          -  Documentation of at least one of the following: ANA titer &gt;= 1:160 or positive&#xD;
             anti-dsDNA antibodies.&#xD;
&#xD;
          -  Stable systemic lupus erythematosus medication regimen.&#xD;
&#xD;
          -  Other than systemic lupus erythematosus, subject should be in general good health.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Male.&#xD;
&#xD;
          -  Drug-induced or highly active systemic lupus erythematosus.&#xD;
&#xD;
          -  Significant autoimmune disease other than lupus.&#xD;
&#xD;
          -  Significant, uncontrolled or unstable disease in any organ.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peng Lu, MD</last_name>
    <role>Study Director</role>
    <affiliation>AbbVie</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 89694</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33765</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 131720</name>
      <address>
        <city>DeBary</city>
        <state>Florida</state>
        <zip>32713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 124116</name>
      <address>
        <city>Miami Lakes</city>
        <state>Florida</state>
        <zip>33016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 118637</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 89693</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 78256</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 129826</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 89773</name>
      <address>
        <city>Manhasset</city>
        <state>New York</state>
        <zip>11030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 78254</name>
      <address>
        <city>Duncansville</city>
        <state>Pennsylvania</state>
        <zip>16635</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 123335</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 78253</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 107896</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 116395</name>
      <address>
        <city>Distrito Federal</city>
        <zip>CP 14050</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 112555</name>
      <address>
        <city>Monterrey</city>
        <zip>C.P. 64000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 132009</name>
      <address>
        <city>San Juan</city>
        <zip>00909-3004</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Mexico</country>
    <country>Puerto Rico</country>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Lu P, Fleischmann R, Curtis C, Ignatenko S, Clarke SH, Desai M, Wong SL, Grebe KM, Black K, Zeng J, Stolzenbach J, Medema JK. Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and multiple ascending dose study in women with systemic lupus erythematosus. Lupus. 2018 Feb;27(2):290-302. doi: 10.1177/0961203317719334. Epub 2017 Jul 10.</citation>
    <PMID>28691866</PMID>
  </results_reference>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>September 13, 2012</study_first_submitted>
  <study_first_submitted_qc>September 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2012</study_first_posted>
  <last_update_submitted>November 16, 2017</last_update_submitted>
  <last_update_submitted_qc>November 16, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lupus Erythematosus, Systemic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Venetoclax</mesh_term>
  </intervention_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/NCT01686555
org study id: M13-093
secondary id: 2013-000328-33
nct id: NCT01686555
lead sponsor: 
has dmc: No
To assess the safety, tolerability and pharmacokinetics of ABT-199 in female subjects with
      Systemic Lupus Erythematosus.
This is a phase 1, randomized, double-blind, placebo-controlled, single-and multiple
      ascending dose study. Up to eighty-eight subjects with Systemic Lupus Erythematosus will be
      selected to participate. Subjects will be randomized to receive either ABT-199 or placebo.
      Subjects will be administered ABT-199/placebo as a single dose or up to 14 days as multiple
      doses.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Number of participants with Adverse Events
time frame: From first dose of ABT-199 until 28 days after single dose of ABT-199 and until 21 days after the last multiple dose of ABT-199
description: Collect all adverse events at each visit
measure: Physical Exam including vital signs
time frame: Prior to the first dose of ABT-199 until 28 days after single dose of ABT-199 and until 21 days after the last multiple dose of ABT-199
description: Blood pressure, heart rate and body temperature
measure: Clinical Lab Testing
time frame: Prior to the first dose of ABT-199 until 28 days after single dose of ABT-199 and until 21 days after the last multiple dose of ABT-199
description: Hematology, Chemistry, and Urinalysis
measure: Electrocardiogram (ECG) Measurements
time frame: For 24 hours after a single dose of ABT-199 and up to 24 hours after the seventh dose of multiple doses of ABT-199
description: ECGs done in triplicate
measure: Maximum observed serum concentration (Cmax) of ABT-199
time frame: For 72 hours after a single dose of ABT-199 and for 24 hours after the seventh dose of multiple doses of ABT-199
description: Cmax
measure: Time to Cmax (Tmax) of ABT-199
time frame: For 72 hours after a single dose of ABT-199 and for 24 hours after the seventh dose of multiple doses of ABT-199
description: Time to Cmax
measure: The area under the time curve (AUC) of ABT-199
time frame: For 72 hours after a single dose of ABT-199 and for 24 hours after the seventh dose of multiple doses of ABT-199
description: the area under the exposure-time curve of ABT-199 extrapolated to infinite time for single doses and up to 24 hrs for multiple doses of ABT-199
measure: The terminal phase elimination rate constant and the terminal elimination half-life (t1/2) of ABT-199
time frame: For 72 hours after a single dose of ABT-199
description: The terminal phase elimination rate constant and the terminal elimination half-life (t1/2) of ABT-199
measure: Measurement of lymphocyte depletion and recovery
time frame: Prior to the first dose of ABT-199 until 28 days after single dose of ABT-199 and until 21 days after the last multiple dose of ABT-199
description: explore pharmacokinetic/pharmacodynamic relationship
arm group label: Single Dose
arm group type: Experimental
description: Subjects enrolled in the Single Ascending Dose (SAD) part of the study will receive a single dose of study drug or placebo. (Groups 1, 2, 3, 4, 5 and 6).
arm group label: Multiple Dose
arm group type: Experimental
description: Subjects enrolled in the Multiple Ascending Dose (MAD) part of the study will receive multiple doses of study drug or placebo. (Groups 7, 8, 9, 10 and 11)
intervention type: Drug
intervention name: ABT-199
description: Tablet
arm group label: Multiple Dose
arm group label: Single Dose
intervention type: Other
intervention name: Placebo
description: Tablet
arm group label: Multiple Dose
arm group label: Single Dose
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Peng Lu, MD
role: Study Director
affiliation: AbbVie
facility: 
facility: 
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facility: 
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country: Germany
country: Mexico
country: Puerto Rico
country: United States
citation: Lu P, Fleischmann R, Curtis C, Ignatenko S, Clarke SH, Desai M, Wong SL, Grebe KM, Black K, Zeng J, Stolzenbach J, Medema JK. Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and multiple ascending dose study in women with systemic lupus erythematosus. Lupus. 2018 Feb;27(2):290-302. doi: 10.1177/0961203317719334. Epub 2017 Jul 10.
PMID: 28691866
responsible party type: Sponsor
mesh term: Lupus Erythematosus, Systemic
mesh term: Venetoclax