<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/NCT04408937</url>
  </required_header>
  <id_info>
    <org_study_id>CLJN452A2113</org_study_id>
    <nct_id>NCT04408937</nct_id>
  </id_info>
  <brief_title>The Purpose of This Study is to Investigate Safety and Tolerability of Tropifexor.</brief_title>
  <official_title>A Randomized, Investigator and Subject Blinded, Multicenter, Parallel-arm Study to Determine the Safety and Tolerability of Tropifexor.</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>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether dosing tropifexor is safe and tolerable.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a randomized, subject and investigator blinded, multicenter, parallel-arm study to&#xD;
      assess the safety and tolerability of tropifexor dosed in the evening as compared to dosing&#xD;
      in the morning in subjects with non-alcoholic steatohepatitis (NASH). Subjects whose&#xD;
      eligibility was confirmed were randomized with stratification by domicile status at Day 1 of&#xD;
      the treatment period into tropifexor (200 μg) AM dose group (hereafter referred to as AM dose&#xD;
      group) or tropifexor (200 μg) PM dose group (hereafter referred to as PM dose group) in a 1:1&#xD;
      ratio. Subjects in the AM dose group took tropifexor in the morning and placebo in the&#xD;
      evening while subjects in the PM dose group took placebo in the morning and tropifexor in the&#xD;
      evening for 4 weeks in a blinded manner.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 29, 2020</start_date>
  <completion_date type="Actual">November 4, 2020</completion_date>
  <primary_completion_date type="Actual">November 4, 2020</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in fasting circulating LDL-C levels after 2 weeks of tropifexor treatment</measure>
    <time_frame>week 2</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in fasting circulating High density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels over 4 weeks of treatment</measure>
    <time_frame>week 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ALT, AST and GGT over 4 weeks of treatment</measure>
    <time_frame>week 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters include but not limited to Cmax (ng/ml) will be assessed in the domiciled patients</measure>
    <time_frame>week 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters include but not limited to area under the curve (AUC) will be assessed in the domiciled patients</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">89</enrollment>
  <condition>Liver Disease</condition>
  <arm_group>
    <arm_group_label>tropifexor AM 200 micrograms and Placebo (PM)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tropifexor 200 μg (AM) and Placebo (PM) once daily each</description>
  </arm_group>
  <arm_group>
    <arm_group_label>tropifexor PM 200 micrograms and Placebo (AM)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tropifexor 200 μg (PM) and Placebo (AM) once daily each</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>triopifexor</intervention_name>
    <description>Tropifexor as a dry blend in hard gelatin capsules for oral administration</description>
    <arm_group_label>tropifexor AM 200 micrograms and Placebo (PM)</arm_group_label>
    <arm_group_label>tropifexor PM 200 micrograms and Placebo (AM)</arm_group_label>
    <other_name>LJN452</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo capsules for oral administration</description>
    <arm_group_label>tropifexor AM 200 micrograms and Placebo (PM)</arm_group_label>
    <arm_group_label>tropifexor PM 200 micrograms and Placebo (AM)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        -Presence of Liver Disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of other investigational drugs at the time of enrollment, or within 5 half-lives&#xD;
             of enrollment, or within 30 days, whichever is longer; or longer if required by local&#xD;
             regulations.&#xD;
&#xD;
          -  Subjects taking the following medicines UNLESS on a stable dose (within 25% of&#xD;
             baseline dose) for at least 3 months before randomization:&#xD;
&#xD;
        Type 1 diabetes and Uncontrolled Type 2 diabetes defined as Glycated hemoglobin (HbAlc) ≥&#xD;
        9.5% at screening&#xD;
&#xD;
        -Calculated estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m2 (using the&#xD;
        Modification of diet in renal disease (MDRD) formula) Subjects with contraindications to&#xD;
        Magnetic resonance imaging (MRI) imaging.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madison</city>
        <state>Alabama</state>
        <zip>35758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Coronado</city>
        <state>California</state>
        <zip>92118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33014-3616</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pensacola</city>
        <state>Florida</state>
        <zip>32503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>South Bend</city>
        <state>Indiana</state>
        <zip>46635</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Morehead City</city>
        <state>North Carolina</state>
        <zip>28557</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hermitage</city>
        <state>Tennessee</state>
        <zip>37076</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75208-2312</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=975</url>
    <description>A Plain Language Trial Summary is available on novctrd.com</description>
  </link>
  <link>
    <url>https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17871</url>
    <description>Results for CLJN452A2113 can be found on the Novartis Clinical Trial Results Website.</description>
  </link>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>February 7, 2022</last_update_submitted>
  <last_update_submitted_qc>February 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>tropifexor</keyword>
  <keyword>FXR agonist</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04408937
org study id: CLJN452A2113
nct id: NCT04408937
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine whether dosing tropifexor is safe and tolerable.
This was a randomized, subject and investigator blinded, multicenter, parallel-arm study to
      assess the safety and tolerability of tropifexor dosed in the evening as compared to dosing
      in the morning in subjects with non-alcoholic steatohepatitis (NASH). Subjects whose
      eligibility was confirmed were randomized with stratification by domicile status at Day 1 of
      the treatment period into tropifexor (200 μg) AM dose group (hereafter referred to as AM dose
      group) or tropifexor (200 μg) PM dose group (hereafter referred to as PM dose group) in a 1:1
      ratio. Subjects in the AM dose group took tropifexor in the morning and placebo in the
      evening while subjects in the PM dose group took placebo in the morning and tropifexor in the
      evening for 4 weeks in a blinded manner.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change from baseline in fasting circulating LDL-C levels after 2 weeks of tropifexor treatment
time frame: week 2
measure: Change in fasting circulating High density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels over 4 weeks of treatment
time frame: week 4
measure: Change in ALT, AST and GGT over 4 weeks of treatment
time frame: week 4
measure: PK parameters include but not limited to Cmax (ng/ml) will be assessed in the domiciled patients
time frame: week 4
measure: PK parameters include but not limited to area under the curve (AUC) will be assessed in the domiciled patients
time frame: 4 weeks
arm group label: tropifexor AM 200 micrograms and Placebo (PM)
arm group type: Experimental
description: Tropifexor 200 μg (AM) and Placebo (PM) once daily each
arm group label: tropifexor PM 200 micrograms and Placebo (AM)
arm group type: Experimental
description: Tropifexor 200 μg (PM) and Placebo (AM) once daily each
intervention type: Drug
intervention name: triopifexor
description: Tropifexor as a dry blend in hard gelatin capsules for oral administration
arm group label: tropifexor AM 200 micrograms and Placebo (PM)
arm group label: tropifexor PM 200 micrograms and Placebo (AM)
other name: LJN452
intervention type: Drug
intervention name: Placebo
description: Placebo capsules for oral administration
arm group label: tropifexor AM 200 micrograms and Placebo (PM)
arm group label: tropifexor PM 200 micrograms and Placebo (AM)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=975
description: A Plain Language Trial Summary is available on novctrd.com
url: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17871
description: Results for CLJN452A2113 can be found on the Novartis Clinical Trial Results Website.
responsible party type: Sponsor
mesh term: Liver Diseases
sharing ipd: No