<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/NCT01675154</url>
  </required_header>
  <id_info>
    <org_study_id>3940</org_study_id>
    <secondary_id>FD-R-003940</secondary_id>
    <nct_id>NCT01675154</nct_id>
  </id_info>
  <brief_title>Phase 2 Study of Orlistat and SLx-4090 for the Treatment of Type 1 Hyperlipoproteinemia</brief_title>
  <official_title>Phase 2 Study of Orlistat and SLx-4090 for the Treatment of Type 1 Hyperlipoproteinemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Funding Source - FDA OOPD&#xD;
&#xD;
      This study is being done to find out whether an investigational (not approved by FDA ) drug&#xD;
      called SLx-4090 or Orlistat (FDA approved medication for weight loss) when given alone or in&#xD;
      combination can treat the high blood fat (elevated triglycerides)levels found in the&#xD;
      condition Type 1 Hyperlipoproteinemia (T1HLP) better or more safely than low fat diet alone,&#xD;
      the current standard medical care.&#xD;
&#xD;
      It is also not clear whether Orlistat, that is FDA approved for weight loss, is effective in&#xD;
      lowering blood fat levels in patients with Type 1 hyperlipoproteinemia (T1HLP). The&#xD;
      researchers are interested in learning whether any one of these drugs when given alone or in&#xD;
      combination is more effective and safe in treating T1HLP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Type I hyperlipoproteinemia is a rare, autosomal recessive metabolic disorder characterized&#xD;
      by extreme hypertriglyceridemia due to a deficiency in lipoprotein lipase or related&#xD;
      proteins. Treatment of these patients is challenging as triglyceride-lowering medications are&#xD;
      ineffective. A low fat diet is helpful, however, despite good dietary compliance, some&#xD;
      patients continue to have severe hypertriglyceridemia and recurrent pancreatitis which can be&#xD;
      life threatening. Therefore, we wish to investigate whether inducing dietary fat&#xD;
      malabsorption or inhibiting chylomicron formation will cause further lowering of serum&#xD;
      triglycerides (TG) beyond the effect of limiting dietary fat intake.&#xD;
&#xD;
      We will study the efficacy and safety of an inhibitor of intestinal lipase (Orlistat) and an&#xD;
      intestinal-specific inhibitor of microsomal triglyceride transport protein (MTP) involved in&#xD;
      the assembly and secretion of chylomicrons (SLx-4090), alone and in combination, for reducing&#xD;
      serum triglyceride levels in patients with Type I hyperlipoproteinemia. We plan to enroll 20&#xD;
      patients with Type I hyperlipoproteinemia in a randomized, double-blind, placebo-controlled,&#xD;
      cross-over trial. After a baseline evaluation, the subjects will be randomly assigned to&#xD;
      placebo/placebo, Orlistat/placebo, SLx-4090/placebo or Orlistat/SLx-4090 for the duration of&#xD;
      four weeks followed by a one week wash out period. During the last week of each study period,&#xD;
      fasting blood samples will be drawn for three consecutive days for serum lipids and chemistry&#xD;
      panel. The primary endpoint will be serum triglycerides; the secondary endpoint variables&#xD;
      will be fasting and postprandial serum chylomicron-TG levels, postprandial serum TG levels&#xD;
      during a meal tolerance test and retinyl palmitate levels during a meal tolerance test.&#xD;
      Repeated measures analysis of variance will be used for statistical comparisons.&#xD;
&#xD;
      Our results may help in designing novel therapeutic approaches for patients with Type 1&#xD;
      hyperlipoproteinemia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to unavailability of the drug.&#xD;
  </why_stopped>
  <start_date type="Actual">November 2015</start_date>
  <completion_date type="Actual">June 30, 2020</completion_date>
  <primary_completion_date type="Actual">June 30, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>This trial is adaptive design/flexible design. The participants were randomized from the start of the study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Serum Triglycerides at First Intervention Period</measure>
    <time_frame>4 weeks after the assigned treatment (first intervention period)</time_frame>
    <description>Serum triglyceride level will be measured after taking each assigned intervention at first intervention period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum Triglycerides at Second Intervention Period</measure>
    <time_frame>4 weeks after the assigned treatment (Second Intervention Period)</time_frame>
    <description>Serum triglyceride level will be measured after taking each assigned intervention at second intervention period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum Triglycerides at Third Intervention Period</measure>
    <time_frame>4 weeks after the assigned treatment (Third Intervention Period)</time_frame>
    <description>Serum triglyceride level will be measured after taking each assigned intervention at intervention period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum Triglycerides at Fourth Intervention Period</measure>
    <time_frame>4 weeks after the assigned treatment (Fourth Intervention Period)</time_frame>
    <description>Serum triglyceride level will be measured after taking each assigned intervention at fourth intervention period</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Type 1 Hyperlipoproteinemia</condition>
  <arm_group>
    <arm_group_label>SLx-4090 placebo/Orlistat Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Slx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.&#xD;
Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.&#xD;
This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Orlistat/placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Orlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Orlistat placebo /SLx-4090</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Orlistat placebo 2 capsules, 60mg each three times per day with meals. Slx-4090 4 tablets, 50mg each. three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Orlistat/SLx-4090</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SLx-4090 placebo</intervention_name>
    <description>Given for 4 weeks</description>
    <arm_group_label>Orlistat/placebo</arm_group_label>
    <arm_group_label>SLx-4090 placebo/Orlistat Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Orlistat Placebo</intervention_name>
    <description>Given for 4 weeks</description>
    <arm_group_label>Orlistat placebo /SLx-4090</arm_group_label>
    <arm_group_label>SLx-4090 placebo/Orlistat Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Orlistat</intervention_name>
    <description>Given for 4 weeks</description>
    <arm_group_label>Orlistat/SLx-4090</arm_group_label>
    <arm_group_label>Orlistat/placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Slx-4090</intervention_name>
    <description>Given for 4 weeks</description>
    <arm_group_label>Orlistat placebo /SLx-4090</arm_group_label>
    <arm_group_label>Orlistat/SLx-4090</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type I hyperlipoproteinemia.&#xD;
&#xD;
          -  Fasting serum triglyceride levels of greater than 1000 mg/dL.&#xD;
&#xD;
          -  Age &gt; 12 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Secondary hypertriglyceridemias due to diabetes, renal disease, hypothyroidism,&#xD;
             alcoholism and drug therapy such as estrogens and estrogen analogues, steroids,&#xD;
             HIV-protease inhibitors, retinoic acid derivatives and interferons.&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Significant liver disease (elevated transaminases &gt; 2 times upper limit of normal)&#xD;
&#xD;
          -  Alcohol abuse (&gt; 7 drinks or 84 g per week for women and &gt; 14 drinks for men or 168 g&#xD;
             per week for men)&#xD;
&#xD;
          -  Drug use (cocaine, marijuana, LSD, etc.)&#xD;
&#xD;
          -  Major surgery in the past three months&#xD;
&#xD;
          -  Congestive heart failure&#xD;
&#xD;
          -  Serum creatinine greater than 2.5 mg/dL&#xD;
&#xD;
          -  Cancer within the past five years&#xD;
&#xD;
          -  Gastrointestinal surgery in the past&#xD;
&#xD;
          -  Current therapy with anti-coagulants, digoxin and anti-arrhythmics&#xD;
&#xD;
          -  Chronic malabsorption syndromes&#xD;
&#xD;
          -  Cholestasis&#xD;
&#xD;
          -  Acute illnesses such as acute pancreatitis in the last 8 weeks&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Abhimanyu Garg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UT Southwestern Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UT Southwestern Medical Center 5323 Harry Hines Blvd</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-8537</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>August 27, 2012</study_first_submitted>
  <study_first_submitted_qc>August 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2012</study_first_posted>
  <results_first_submitted>May 21, 2021</results_first_submitted>
  <results_first_submitted_qc>July 26, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 19, 2021</results_first_posted>
  <last_update_submitted>July 26, 2021</last_update_submitted>
  <last_update_submitted_qc>July 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
    <investigator_full_name>Abhimanyu Garg</investigator_full_name>
    <investigator_title>PI</investigator_title>
  </responsible_party>
  <keyword>hypertriglyceridemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperlipoproteinemias</mesh_term>
    <mesh_term>Hyperlipidemias</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Orlistat</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 28, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/54/NCT01675154/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This trial is adaptive design/flexible design. The participants were randomized from the start of the study</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>SLx-4090 Placebo/Orlistat Placebo First</title>
          <description>First, SLx-4090 (placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.&#xD;
Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat Placebo: Given for 4 weeks</description>
        </group>
        <group group_id="P2">
          <title>Orlistat/SLx-4090 Placebo</title>
          <description>Then, Orlistat two capsules 60 mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50 mg each, three times per day with meals were administered&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat: Given for 4 weeks</description>
        </group>
        <group group_id="P3">
          <title>Orlistat Placebo /SLx-4090</title>
          <description>Then, Orlistat placebo 2 capsules, 60 mg each three times per day with meals. SLx-4090 4 tablets, 50 mg each. three times per day with meals were administered&#xD;
Orlistat Placebo: Given for 4 weeks&#xD;
SLx-4090: Given for 4 weeks</description>
        </group>
        <group group_id="P4">
          <title>Orlistat/SLx-4090</title>
          <description>Then, Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50 mg each, three times per day with meals were administered&#xD;
Orlistat: Given for 4 weeks&#xD;
SLx-4090: Given for 4 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Intervention Period (4 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>First Washout Period (1 Week)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2">Subjects were enrolled Regimen 1</participants>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Second Intervention Period (4 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1">Subjects were enrolled in Regimen 2</participants>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Second Washout Period (1 Week)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Third Intervention Period (4 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Third Washout Period (1 Week)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Fourth Intervention Period (4 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The baseline characteristics are based on first intervention period assignment. This trial is an adaptive design/flexible design using responsive adaptive randomization. The participants were randomized from the start of the study</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo/Placebo at First Intervention Period</title>
          <description>Slx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.&#xD;
Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.</description>
        </group>
        <group group_id="B2">
          <title>Orlistat/Placebo at First Intervention Period</title>
          <description>Orlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals were administered.</description>
        </group>
        <group group_id="B3">
          <title>Orlistat Placebo /Slx-4090 at First Intervention Period</title>
          <description>Orlistat placebo 2 capsules, 60mg each three times per day with meals. Slx-4090 4 tablets, 50mg each. three times per day with meals were administered</description>
        </group>
        <group group_id="B4">
          <title>Orlistat/SLx-4090 at First Intervention Period</title>
          <description>Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals were administered.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="2"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="1"/>
            <count group_id="B4" value="1"/>
            <count group_id="B5" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt;18.5 kg/m^2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18.5 kg/m^2-24.9 kg/m^2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 kg/m^2-29.9 kg/m^2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 kg/m^2-34.9 kg/m^2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>35 kg/m^2-39.9 kg/m^2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=40 kg/m^2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Triglycerides</title>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1969" spread="419"/>
                    <measurement group_id="B2" value="4840" spread="0"/>
                    <measurement group_id="B3" value="814" spread="0"/>
                    <measurement group_id="B4" value="2061" spread="0"/>
                    <measurement group_id="B5" value="2421" spread="1480"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Serum Triglycerides at First Intervention Period</title>
        <description>Serum triglyceride level will be measured after taking each assigned intervention at first intervention period.</description>
        <time_frame>4 weeks after the assigned treatment (first intervention period)</time_frame>
        <population>This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>SLx-4090 Placebo/Orlistat Placebo</title>
            <description>Slx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.&#xD;
Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat Placebo: Given for 4 weeks</description>
          </group>
          <group group_id="O2">
            <title>Orlistat/Placebo</title>
            <description>Orlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat: Given for 4 weeks</description>
          </group>
          <group group_id="O3">
            <title>Orlistat Placebo /Slx-4090</title>
            <description>Orlistat placebo 2 capsules, 60mg each three times per day with meals. Slx-4090 4 tablets, 50mg each. three times per day with meals.&#xD;
Orlistat Placebo: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
          </group>
          <group group_id="O4">
            <title>Orlistat/SLx-4090</title>
            <description>Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals.&#xD;
Orlistat: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Triglycerides at First Intervention Period</title>
          <description>Serum triglyceride level will be measured after taking each assigned intervention at first intervention period.</description>
          <population>This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.</population>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="1"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2086" spread="481.54"/>
                    <measurement group_id="O2" value="3320"/>
                    <measurement group_id="O3" value="1576"/>
                    <measurement group_id="O4" value="1280"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Serum Triglycerides at Second Intervention Period</title>
        <description>Serum triglyceride level will be measured after taking each assigned intervention at second intervention period</description>
        <time_frame>4 weeks after the assigned treatment (Second Intervention Period)</time_frame>
        <population>Patient assigned to SLX-4090 placebo/Orlistat placebo group withdrew from the study in this phase.&#xD;
One more subject was assigned to the Orlistat/SLx-4090 but could not start the study as the drug SLx-4090 was not available.&#xD;
This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>SLx-4090 Placebo/Orlistat Placebo</title>
            <description>Slx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.&#xD;
Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat Placebo: Given for 4 weeks</description>
          </group>
          <group group_id="O2">
            <title>Orlistat/Placebo</title>
            <description>Orlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat: Given for 4 weeks</description>
          </group>
          <group group_id="O3">
            <title>Orlistat Placebo /Slx-4090</title>
            <description>Orlistat placebo 2 capsules, 60mg each three times per day with meals. Slx-4090 4 tablets, 50mg each. three times per day with meals.&#xD;
Orlistat Placebo: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
          </group>
          <group group_id="O4">
            <title>Orlistat/SLx-4090</title>
            <description>Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals.&#xD;
Orlistat: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Triglycerides at Second Intervention Period</title>
          <description>Serum triglyceride level will be measured after taking each assigned intervention at second intervention period</description>
          <population>Patient assigned to SLX-4090 placebo/Orlistat placebo group withdrew from the study in this phase.&#xD;
One more subject was assigned to the Orlistat/SLx-4090 but could not start the study as the drug SLx-4090 was not available.&#xD;
This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.</population>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="1"/>
                <count group_id="O4" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="1419"/>
                    <measurement group_id="O3" value="2040"/>
                    <measurement group_id="O4" value="3478"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Serum Triglycerides at Third Intervention Period</title>
        <description>Serum triglyceride level will be measured after taking each assigned intervention at intervention period</description>
        <time_frame>4 weeks after the assigned treatment (Third Intervention Period)</time_frame>
        <population>Patient assigned to Orlistat/SLX-4090 placebo group did not start the assigned treatment due to lack of drugs.&#xD;
This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>SLx-4090 Placebo/Orlistat Placebo</title>
            <description>Slx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.&#xD;
Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat Placebo: Given for 4 weeks</description>
          </group>
          <group group_id="O2">
            <title>Orlistat/Placebo</title>
            <description>Orlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat: Given for 4 weeks</description>
          </group>
          <group group_id="O3">
            <title>Orlistat Placebo /Slx-4090</title>
            <description>Orlistat placebo 2 capsules, 60mg each three times per day with meals. Slx-4090 4 tablets, 50mg each. three times per day with meals.&#xD;
Orlistat Placebo: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
          </group>
          <group group_id="O4">
            <title>Orlistat/SLx-4090</title>
            <description>Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals.&#xD;
Orlistat: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Triglycerides at Third Intervention Period</title>
          <description>Serum triglyceride level will be measured after taking each assigned intervention at intervention period</description>
          <population>Patient assigned to Orlistat/SLX-4090 placebo group did not start the assigned treatment due to lack of drugs.&#xD;
This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.</population>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="1"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6220"/>
                    <measurement group_id="O3" value="1320"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Serum Triglycerides at Fourth Intervention Period</title>
        <description>Serum triglyceride level will be measured after taking each assigned intervention at fourth intervention period</description>
        <time_frame>4 weeks after the assigned treatment (Fourth Intervention Period)</time_frame>
        <population>Patient assigned to Orlistat/SLX-4090 group did not start the assigned treatment due to lack of drugs.&#xD;
This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>SLx-4090 Placebo/Orlistat Placebo</title>
            <description>Slx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.&#xD;
Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat Placebo: Given for 4 weeks</description>
          </group>
          <group group_id="O2">
            <title>Orlistat/Placebo</title>
            <description>Orlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat: Given for 4 weeks</description>
          </group>
          <group group_id="O3">
            <title>Orlistat Placebo /Slx-4090</title>
            <description>Orlistat placebo 2 capsules, 60mg each three times per day with meals. Slx-4090 4 tablets, 50mg each. three times per day with meals.&#xD;
Orlistat Placebo: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
          </group>
          <group group_id="O4">
            <title>Orlistat/SLx-4090</title>
            <description>Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals.&#xD;
Orlistat: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Triglycerides at Fourth Intervention Period</title>
          <description>Serum triglyceride level will be measured after taking each assigned intervention at fourth intervention period</description>
          <population>Patient assigned to Orlistat/SLX-4090 group did not start the assigned treatment due to lack of drugs.&#xD;
This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.</population>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="1"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1156"/>
                    <measurement group_id="O3" value="2946"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Over a period of 1 year .</time_frame>
      <desc>This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.&#xD;
Includes all participants who started first, second, third and fourth intervention periods. Events were collected separately for each period.</desc>
      <group_list>
        <group group_id="E1">
          <title>1st Intervention Period:SLx-4090 Placebo/Orlistat Placebo</title>
          <description>Slx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.&#xD;
Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat Placebo: Given for 4 weeks</description>
        </group>
        <group group_id="E2">
          <title>1st Intervention Period:Orlistat/Placebo</title>
          <description>Orlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat: Given for 4 weeks</description>
        </group>
        <group group_id="E3">
          <title>1st Intervention Period:Orlistat Placebo /Slx-4090</title>
          <description>Orlistat placebo 2 capsules, 60mg each three times per day with meals. Slx-4090 4 tablets, 50mg each. three times per day with meals.&#xD;
Orlistat Placebo: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
        </group>
        <group group_id="E4">
          <title>1st Intervention Period:Orlistat/SLx-4090</title>
          <description>Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals.&#xD;
Orlistat: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
        </group>
        <group group_id="E5">
          <title>2nd Intervention Period:SLx-4090 Placebo/Orlistat Placebo</title>
          <description>Slx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.&#xD;
Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat Placebo: Given for 4 weeks</description>
        </group>
        <group group_id="E6">
          <title>2nd Intervention Period:Orlistat/Placebo</title>
          <description>Orlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat: Given for 4 weeks</description>
        </group>
        <group group_id="E7">
          <title>2nd Intervention Period:Orlistat Placebo /Slx-4090</title>
          <description>Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals.&#xD;
Orlistat: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
        </group>
        <group group_id="E8">
          <title>2nd Intervention Period:Orlistat/SLx-4090</title>
          <description>Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals.&#xD;
Orlistat: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
        </group>
        <group group_id="E9">
          <title>3rd Intervention Period:SLx-4090 Placebo/Orlistat Placebo</title>
          <description>Slx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.&#xD;
Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat Placebo: Given for 4 weeks</description>
        </group>
        <group group_id="E10">
          <title>3rd Intervention Period:Orlistat/Placebo</title>
          <description>Orlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat: Given for 4 weeks</description>
        </group>
        <group group_id="E11">
          <title>3rd Intervention Period:Orlistat Placebo /Slx-4090</title>
          <description>Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals.&#xD;
Orlistat: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
        </group>
        <group group_id="E12">
          <title>3rd Intervention Period:Orlistat/SLx-4090</title>
          <description>Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals.&#xD;
Orlistat: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
        </group>
        <group group_id="E13">
          <title>4th Intervention Period:SLx-4090 Placebo/Orlistat Placebo</title>
          <description>Slx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.&#xD;
Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat Placebo: Given for 4 weeks</description>
        </group>
        <group group_id="E14">
          <title>4th Intervention Period:Orlistat/Placebo</title>
          <description>Orlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals.&#xD;
SLx-4090 placebo: Given for 4 weeks&#xD;
Orlistat: Given for 4 weeks</description>
        </group>
        <group group_id="E15">
          <title>4th Intervention Period:Orlistat Placebo /Slx-4090</title>
          <description>Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals.&#xD;
Orlistat: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
        </group>
        <group group_id="E16">
          <title>4th Intervention Period:Orlistat/SLx-4090</title>
          <description>Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals.&#xD;
Orlistat: Given for 4 weeks&#xD;
Slx-4090: Given for 4 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Pancreatitis.</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Increased urgency of passing stool</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Only five patients were enrolled in the study. Two patients completed the study. One subject dropped our after Second Intervention Period. Participation of other two subjects was halted due to unavailability of study medications.&#xD;
Study Design: Although protocol states &quot;This trial is randomized, double-blind cross-over trial&quot;, study design was actually not a cross over design, but adaptive/flexible design using a responsive adaptive randomization. Thus Arm/Group were not listed &quot;per sequence&quot;.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Abhimanyu Garg</name_or_title>
      <organization>UT Southwestern Medical Center</organization>
      <phone>214-648-8295</phone>
      <email>abhimanyu.garg@utsouthwestern.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01675154
org study id: 3940
secondary id: FD-R-003940
nct id: NCT01675154
lead sponsor: 
has dmc: Yes
Funding Source - FDA OOPD

      This study is being done to find out whether an investigational (not approved by FDA ) drug
      called SLx-4090 or Orlistat (FDA approved medication for weight loss) when given alone or in
      combination can treat the high blood fat (elevated triglycerides)levels found in the
      condition Type 1 Hyperlipoproteinemia (T1HLP) better or more safely than low fat diet alone,
      the current standard medical care.

      It is also not clear whether Orlistat, that is FDA approved for weight loss, is effective in
      lowering blood fat levels in patients with Type 1 hyperlipoproteinemia (T1HLP). The
      researchers are interested in learning whether any one of these drugs when given alone or in
      combination is more effective and safe in treating T1HLP.
Type I hyperlipoproteinemia is a rare, autosomal recessive metabolic disorder characterized
      by extreme hypertriglyceridemia due to a deficiency in lipoprotein lipase or related
      proteins. Treatment of these patients is challenging as triglyceride-lowering medications are
      ineffective. A low fat diet is helpful, however, despite good dietary compliance, some
      patients continue to have severe hypertriglyceridemia and recurrent pancreatitis which can be
      life threatening. Therefore, we wish to investigate whether inducing dietary fat
      malabsorption or inhibiting chylomicron formation will cause further lowering of serum
      triglycerides (TG) beyond the effect of limiting dietary fat intake.

      We will study the efficacy and safety of an inhibitor of intestinal lipase (Orlistat) and an
      intestinal-specific inhibitor of microsomal triglyceride transport protein (MTP) involved in
      the assembly and secretion of chylomicrons (SLx-4090), alone and in combination, for reducing
      serum triglyceride levels in patients with Type I hyperlipoproteinemia. We plan to enroll 20
      patients with Type I hyperlipoproteinemia in a randomized, double-blind, placebo-controlled,
      cross-over trial. After a baseline evaluation, the subjects will be randomly assigned to
      placebo/placebo, Orlistat/placebo, SLx-4090/placebo or Orlistat/SLx-4090 for the duration of
      four weeks followed by a one week wash out period. During the last week of each study period,
      fasting blood samples will be drawn for three consecutive days for serum lipids and chemistry
      panel. The primary endpoint will be serum triglycerides; the secondary endpoint variables
      will be fasting and postprandial serum chylomicron-TG levels, postprandial serum TG levels
      during a meal tolerance test and retinyl palmitate levels during a meal tolerance test.
      Repeated measures analysis of variance will be used for statistical comparisons.

      Our results may help in designing novel therapeutic approaches for patients with Type 1
      hyperlipoproteinemia.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: This trial is adaptive design/flexible design. The participants were randomized from the start of the study
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Serum Triglycerides at First Intervention Period
time frame: 4 weeks after the assigned treatment (first intervention period)
description: Serum triglyceride level will be measured after taking each assigned intervention at first intervention period.
measure: Serum Triglycerides at Second Intervention Period
time frame: 4 weeks after the assigned treatment (Second Intervention Period)
description: Serum triglyceride level will be measured after taking each assigned intervention at second intervention period
measure: Serum Triglycerides at Third Intervention Period
time frame: 4 weeks after the assigned treatment (Third Intervention Period)
description: Serum triglyceride level will be measured after taking each assigned intervention at intervention period
measure: Serum Triglycerides at Fourth Intervention Period
time frame: 4 weeks after the assigned treatment (Fourth Intervention Period)
description: Serum triglyceride level will be measured after taking each assigned intervention at fourth intervention period
arm group label: SLx-4090 placebo/Orlistat Placebo
arm group type: Placebo Comparator
description: Slx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.
Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.
This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.
arm group label: Orlistat/placebo
arm group type: Experimental
description: Orlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.
arm group label: Orlistat placebo /SLx-4090
arm group type: Experimental
description: Orlistat placebo 2 capsules, 60mg each three times per day with meals. Slx-4090 4 tablets, 50mg each. three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.
arm group label: Orlistat/SLx-4090
arm group type: Experimental
description: Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.
intervention type: Drug
intervention name: SLx-4090 placebo
description: Given for 4 weeks
arm group label: Orlistat/placebo
arm group label: SLx-4090 placebo/Orlistat Placebo
intervention type: Drug
intervention name: Orlistat Placebo
description: Given for 4 weeks
arm group label: Orlistat placebo /SLx-4090
arm group label: SLx-4090 placebo/Orlistat Placebo
intervention type: Drug
intervention name: Orlistat
description: Given for 4 weeks
arm group label: Orlistat/SLx-4090
arm group label: Orlistat/placebo
intervention type: Drug
intervention name: Slx-4090
description: Given for 4 weeks
arm group label: Orlistat placebo /SLx-4090
arm group label: Orlistat/SLx-4090
criteria: 
gender: All
minimum age: 12 Years
maximum age: 100 Years
healthy volunteers: No
last name: Abhimanyu Garg, MD
role: Principal Investigator
affiliation: UT Southwestern Medical Center
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Texas Southwestern Medical Center
investigator full name: Abhimanyu Garg
investigator title: PI
mesh term: Hyperlipoproteinemias
mesh term: Hyperlipidemias
mesh term: Orlistat
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Only five patients were enrolled in the study. Two patients completed the study. One subject dropped our after Second Intervention Period. Participation of other two subjects was halted due to unavailability of study medications.
Study Design: Although protocol states "This trial is randomized, double-blind cross-over trial", study design was actually not a cross over design, but adaptive/flexible design using a responsive adaptive randomization. Thus Arm/Group were not listed "per sequence".
point of contact: 