<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/NCT03012828</url>
  </required_header>
  <id_info>
    <org_study_id>MDGH-MOX-1008</org_study_id>
    <nct_id>NCT03012828</nct_id>
  </id_info>
  <brief_title>Effect of a Single Oral Dose of Moxidectin on the Cardiac QT Interval of Healthy Volunteers</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Potential Effect of a Single Oral Dose of Moxidectin on the Cardiac QT Interval of Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medicines Development for Global Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medicines Development for Global Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will investigate the effect of a single oral dose of moxidectin on the QT interval&#xD;
      associated with moxidectin plasma concentrations.&#xD;
&#xD;
      The effect of moxidectin on other ECG intervals, and on safety, will also be assessed, as&#xD;
      will preliminary pharmacokinetics and metabolism&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Moxidectin is being developed as a treatment for Onchocerciasis (river blindness), a serious,&#xD;
      debilitating, disease caused by a parasitic worm, Onchocerca volvulus.&#xD;
&#xD;
      Five dose levels of moxidectin will be administered to healthy volunteers and ECG assessments&#xD;
      undertaken at pre-specified pharmacokinetic time points to correlate QT interval with&#xD;
      moxidectin concentration in plasma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2017</start_date>
  <completion_date type="Actual">May 2017</completion_date>
  <primary_completion_date type="Actual">March 2017</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Change From Baseline in QTc Interval (Corrected by Friderica's Formula, dQTcF) Associated With Plasma Moxidectin Concentrations After a Single Dose</measure>
    <time_frame>Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing</time_frame>
    <description>Triplicate 10-second ECG recordings taken 1 minute apart using a Mortara continuous 12-lead digital ECG recorder connected to each subject during the Baseline to 72-hour post dose confinement period. Baseline only and baseline and placebo adjusted changes in QTc interval (corrected using the Friderica formula, QTcF) at each timepoint for each dose level were determined. The mean change from baseline (without and with placebo correction, dQTcF and ddQTcF respectively) at each of the 14 time points was calculated for each dose level. The primary outcome measure was the mean dQTcF for all subjects(the dQTcF gradient). The mean dQTcF for each active treatment group was determined at each post dose timepoint but the mean dQTcF by dose level was not calculated. The mean dQTcF at approximate moxidectin Tmax (hour 3 or hour 4) for each active treatment group and at hour 3 for the placebo group is reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concentrations of Moxidectin in Plasma</measure>
    <time_frame>Pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12*, 24, 36, 48, 60, and 72 hours and days 8,15 and 22 post dosing</time_frame>
    <description>Concentrations of moxidectin in plasma were assessed by collection of plasma samples at pre-specified intervals after oral dosing with moxidectin. The concentration of moxidectin was determined using a validated LC MS/MS method.The pharmacokinetic time points coincided with ECG collection timepoints (within 5 minutes and no later than 10 minutes after ECG recordings). Plasma PK parameters were estimated from the concentration measurements, including maximum concentration (Cmax) for each individual and mean for each dose cohort.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Subjects With Categorical Changes From Baseline in 12-lead Electrocardiograms (ECGs)</measure>
    <time_frame>At Baseline and Days 1, 2, 3, 4, 22 and Week 12</time_frame>
    <description>Changes from baseline in QTcF exceeding regulatory standard categorical limits (&gt; 30msec change or exceeding 450msec). Report applies to changes of 30msec - &lt;/= 60msec only</description>
  </other_outcome>
  <other_outcome>
    <measure>Change From Baseline in Heart Rate (HR) and Duration of Other Interval Parameters (PR and QRS)</measure>
    <time_frame>Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing</time_frame>
    <description>Changes from Baseline were assessed at each timepoint up to 72 hours post dose. Mean changes across the 72 hour assessment period for each parameter were calculated for each moxidectin group and the placebo group and for the population overall.</description>
  </other_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>QT Effects in Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Moxidectin 4mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 subjects will receive a single oral dose of moxidectin 4mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moxidectin 8mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 subjects will receive a single oral dose of moxidectin 8mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moxidectin 16mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 subjects will receive a single oral dose of moxidectin 16mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moxidectin 24mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 subjects will receive a single oral dose of moxidectin 24mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moxidectin 36mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 subjects will receive a single oral dose of moxidectin 36mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>10 subjects will receive a single oral dose of placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moxidectin</intervention_name>
    <description>Moxidectin is a broad spectrum macrocyclic lactone endectocide</description>
    <arm_group_label>Moxidectin 16mg</arm_group_label>
    <arm_group_label>Moxidectin 24mg</arm_group_label>
    <arm_group_label>Moxidectin 36mg</arm_group_label>
    <arm_group_label>Moxidectin 4mg</arm_group_label>
    <arm_group_label>Moxidectin 8mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy male between 18 and 50 years of age (inclusive);&#xD;
&#xD;
          2. Body mass index (BMI) of 18 to 30 kg/m2 (inclusive) and a minimum weight of 50 kg (110&#xD;
             lbs);&#xD;
&#xD;
          3. Biologically or surgically sterile or must commit to using a reliable method of birth&#xD;
             control, in the opinion of the investigator, from Screening through the duration of&#xD;
             the study;&#xD;
&#xD;
          4. Willing and able to give written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unwilling to abstain from alcohol, caffeine, xanthine containing products, Seville&#xD;
             oranges, grapefruit juices, and fish liver oils within 72 hours before Check in (Day&#xD;
             -1) and throughout the inpatient period of the study;&#xD;
&#xD;
          2. Less than 1 bowel movement every 24 hours in the absence of any laxative, suppository,&#xD;
             or enema use during the month before Screening;&#xD;
&#xD;
          3. Abnormal fecal consistency within 24 hours of Check in (Day -1);&#xD;
&#xD;
          4. Clinically relevant abnormal findings on medical history, clinical laboratory test&#xD;
             results, vital sign measurements, safety 12 lead ECG results, or physical examination&#xD;
             at Screening or Baseline which, in the opinion of the investigator, would interfere&#xD;
             with dosing, jeopardize the safety of the subject, or impact the validity of the study&#xD;
             results;&#xD;
&#xD;
          5. History of clinically significant dermatologic, gastrointestinal, renal, hepatic,&#xD;
             neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or&#xD;
             cardiovascular disease or any other condition which, in the opinion of the&#xD;
             investigator, would interfere with dosing, jeopardizes the safety of the subject, or&#xD;
             impacts the validity of the study results;&#xD;
&#xD;
          6. History or hypersensitivity or allergic reactions to ivermectin, moxidectin, or any of&#xD;
             the ingredients in the study drug as described in the Investigator's Brochure;&#xD;
&#xD;
          7. Any condition that may affect oral drug absorption (eg, previous surgery on the&#xD;
             gastrointestinal tract including removal of parts of the stomach, bowel, liver, gall&#xD;
             bladder, or pancreas);&#xD;
&#xD;
          8. History of risk factors for torsades de pointes, including unexplained syncope, known&#xD;
             long QT syndrome, heart failure, myocardial infarction, angina, or clinically&#xD;
             significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or&#xD;
             hypomagnesemia. Subjects are also excluded if there is a family history of long QT&#xD;
             syndrome or Brugada syndrome;&#xD;
&#xD;
          9. A sustained supine systolic blood pressure &gt;150 mm Hg or &lt;90 mm Hg or a supine&#xD;
             diastolic blood pressure &gt;95 mm Hg or &lt;50 mm Hg at Screening or Check in (Day -1).&#xD;
             Blood pressure may be retested twice in the supine position. The blood pressure&#xD;
             abnormality is considered sustained if either the systolic or the diastolic blood&#xD;
             pressure values are outside of the stated limits after 3 assessments, and the subject&#xD;
             will not to be randomized;&#xD;
&#xD;
         10. A resting heart rate (HR) of &lt;40 beats per minute (bpm) or &gt;100 bpm when vital signs&#xD;
             are measured at Screening or Check in (Day -1);&#xD;
&#xD;
         11. An uninterpretable or abnormal screening ECG indicating a second or third degree&#xD;
             atrioventricular block, or 1 or more of the following: QRS interval &gt;110 milliseconds&#xD;
             (msec); QT interval corrected by Fridericia's formula (QTcF) &gt;450 msec; PR interval&#xD;
             &gt;200 msec; or any rhythm other than sinus rhythm that is interpreted by the&#xD;
             investigator to be clinically significant;&#xD;
&#xD;
         12. Concomitant use of prescription medications, including medications known to prolong&#xD;
             the corrected QT interval (QTc) or herbal preparations, within 14 days or 5 half-lives&#xD;
             (whichever is longer) before study drug dosing, or use of an over the counter (OTC)&#xD;
             medication or vitamins within 7 days before study drug dosing;&#xD;
&#xD;
         13. Received an investigational drug during the 30 days, or 5 half lives of the study drug&#xD;
             (whichever is longer), before Check in (Day -1) or is planning to receive another&#xD;
             investigational drug at any time during the study;&#xD;
&#xD;
         14. History or presence of alcohol abuse (defined as consumption of more than 210 mL of&#xD;
             alcohol per week, or the equivalent of fourteen 4 ounce [oz] glasses of wine or&#xD;
             fourteen 12 oz cans/bottles of beer or wine coolers per week) within 6 months before&#xD;
             Screening or positive alcohol test at Screening or Check-in (Day -1);&#xD;
&#xD;
         15. History or presence of substance abuse within the past 2 years or positive drug screen&#xD;
             test at Screening or Check in (Day -1);&#xD;
&#xD;
         16. Current use or has used tobacco- or nicotine-containing products (eg, cigarettes,&#xD;
             cigars, chewing tobacco, snuff, etc.) within 14 days before study drug dosing;&#xD;
&#xD;
         17. Blood donation or significant blood loss within 30 days before Check-in (Day -1) or&#xD;
             donated plasma within 7 days before Check-in (Day -1);&#xD;
&#xD;
         18. Presence of hepatitis B surface antigen or antibodies to human immunodeficiency virus&#xD;
             (HIV) or hepatitis C virus at Screening;&#xD;
&#xD;
         19. Poor venous access in both arms;&#xD;
&#xD;
         20. Unable to understand verbal or written English or any other language for which a&#xD;
             certified translation of the informed consent form is available;&#xD;
&#xD;
         21. For any reason, is deemed by the investigator or medically qualified designee to be&#xD;
             inappropriate for this study, including a subject who is unable to communicate or&#xD;
             cooperate with the investigator, and/or is unwilling to comply with protocol defined&#xD;
             procedures and complete the study.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark Sullivan</last_name>
    <role>Study Director</role>
    <affiliation>Sponsor GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Spaulding Clinical</name>
      <address>
        <city>West Bend</city>
        <state>Wisconsin</state>
        <zip>53095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 23, 2016</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <results_first_submitted>December 17, 2017</results_first_submitted>
  <results_first_submitted_qc>March 12, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">March 14, 2019</results_first_posted>
  <last_update_submitted>March 12, 2019</last_update_submitted>
  <last_update_submitted_qc>March 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Moxidectin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Healthy volunteer study: results are not useful to individuals</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 1, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03012828/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 1, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03012828/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Moxidectin 4mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 4mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="P2">
          <title>Moxidectin 8mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 8mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="P3">
          <title>Moxidectin 16mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 16mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="P4">
          <title>Moxidectin 24mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 24mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="P5">
          <title>Moxidectin 36mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 36mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="P6">
          <title>Placebo</title>
          <description>10 subjects will receive a single oral dose of placebo&#xD;
Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="8"/>
                <participants group_id="P6" count="8"/>
              </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="2"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</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 group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance with protocol</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 group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Delay to last visit would delay DBL</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 group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Moxidectin 4mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 4mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="B2">
          <title>Moxidectin 8mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 8mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="B3">
          <title>Moxidectin 16mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 16mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="B4">
          <title>Moxidectin 24mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 24mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="B5">
          <title>Moxidectin 36mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 36mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="B6">
          <title>Placebo</title>
          <description>10 subjects will receive a single oral dose of placebo&#xD;
Placebo</description>
        </group>
        <group group_id="B7">
          <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="10"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="10"/>
            <count group_id="B4" value="10"/>
            <count group_id="B5" value="10"/>
            <count group_id="B6" value="10"/>
            <count group_id="B7" value="60"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37.1" spread="7.77"/>
                    <measurement group_id="B2" value="30.4" spread="8.73"/>
                    <measurement group_id="B3" value="30.9" spread="8.32"/>
                    <measurement group_id="B4" value="31.2" spread="8.27"/>
                    <measurement group_id="B5" value="30.2" spread="8.87"/>
                    <measurement group_id="B6" value="32.3" spread="6.72"/>
                    <measurement group_id="B7" value="32.0" spread="8.15"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="10"/>
                    <measurement group_id="B7" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="10"/>
                    <measurement group_id="B7" value="54"/>
                  </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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" 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="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="5"/>
                    <measurement group_id="B7" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="5"/>
                    <measurement group_id="B7" value="27"/>
                  </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="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                  </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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="10"/>
                    <measurement group_id="B7" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kilogram /meter squared (kg/m2)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.2" spread="3.74"/>
                    <measurement group_id="B2" value="24.9" spread="3.35"/>
                    <measurement group_id="B3" value="25.8" spread="3.71"/>
                    <measurement group_id="B4" value="25.1" spread="3.00"/>
                    <measurement group_id="B5" value="26.7" spread="3.09"/>
                    <measurement group_id="B6" value="26.1" spread="3.11"/>
                    <measurement group_id="B7" value="25.8" spread="3.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Change From Baseline in QTc Interval (Corrected by Friderica's Formula, dQTcF) Associated With Plasma Moxidectin Concentrations After a Single Dose</title>
        <description>Triplicate 10-second ECG recordings taken 1 minute apart using a Mortara continuous 12-lead digital ECG recorder connected to each subject during the Baseline to 72-hour post dose confinement period. Baseline only and baseline and placebo adjusted changes in QTc interval (corrected using the Friderica formula, QTcF) at each timepoint for each dose level were determined. The mean change from baseline (without and with placebo correction, dQTcF and ddQTcF respectively) at each of the 14 time points was calculated for each dose level. The primary outcome measure was the mean dQTcF for all subjects(the dQTcF gradient). The mean dQTcF for each active treatment group was determined at each post dose timepoint but the mean dQTcF by dose level was not calculated. The mean dQTcF at approximate moxidectin Tmax (hour 3 or hour 4) for each active treatment group and at hour 3 for the placebo group is reported.</description>
        <time_frame>Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing</time_frame>
        <population>The ECG population included all subjects who received one dose of study drug and have at least 1 pair of pre-dose and post-dose QTc interval and was used in the model.</population>
        <group_list>
          <group group_id="O1">
            <title>Moxidectin 4mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 4mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O2">
            <title>Moxidectin 8mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 8mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O3">
            <title>Moxidectin 16mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 16mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O4">
            <title>Moxidectin 24mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 24mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O5">
            <title>Moxidectin 36mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 36mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O6">
            <title>Placebo</title>
            <description>10 subjects will receive a single oral dose of placebo&#xD;
Placebo</description>
          </group>
          <group group_id="O7">
            <title>All Subjects</title>
            <description>50 subjects received a single dose of between 4mg and 36mg of moxidectin. 10 subjects received a dose of placebo,</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in QTc Interval (Corrected by Friderica's Formula, dQTcF) Associated With Plasma Moxidectin Concentrations After a Single Dose</title>
          <description>Triplicate 10-second ECG recordings taken 1 minute apart using a Mortara continuous 12-lead digital ECG recorder connected to each subject during the Baseline to 72-hour post dose confinement period. Baseline only and baseline and placebo adjusted changes in QTc interval (corrected using the Friderica formula, QTcF) at each timepoint for each dose level were determined. The mean change from baseline (without and with placebo correction, dQTcF and ddQTcF respectively) at each of the 14 time points was calculated for each dose level. The primary outcome measure was the mean dQTcF for all subjects(the dQTcF gradient). The mean dQTcF for each active treatment group was determined at each post dose timepoint but the mean dQTcF by dose level was not calculated. The mean dQTcF at approximate moxidectin Tmax (hour 3 or hour 4) for each active treatment group and at hour 3 for the placebo group is reported.</description>
          <population>The ECG population included all subjects who received one dose of study drug and have at least 1 pair of pre-dose and post-dose QTc interval and was used in the model.</population>
          <units>millseconds</units>
          <param>Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="10"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="10"/>
                <count group_id="O7" value="60"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.1" lower_limit="-10.90" upper_limit="0.68"/>
                    <measurement group_id="O2" value="-4.5" lower_limit="-9.19" upper_limit="0.27"/>
                    <measurement group_id="O3" value="-4.5" lower_limit="-8.39" upper_limit="-0.63"/>
                    <measurement group_id="O4" value="-6.3" lower_limit="-12.68" upper_limit="0.04"/>
                    <measurement group_id="O5" value="-3.9" lower_limit="-7.77" upper_limit="0.03"/>
                    <measurement group_id="O6" value="-2.9" lower_limit="-6.58" upper_limit="0.76"/>
                    <measurement group_id="O7" value="-0.0077" lower_limit="-0.0255" upper_limit="0.0101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O7</group_id>
            </group_id_list>
            <groups_desc>The primary analysis used a mixed-effects model to explore the relationship between the time-matched, baseline-adjusted QTcF (delta (d)QTcF) and moxidectin concentrations. dQTcF was a dependent variable and treatment, time point, and treatment by time point interaction as the independent variables with baseline QTcF as a covariate and time-matched concentrations of moxidectin as a covariate with random effects of intercept and slope for each subject.Concentrations of zero were used for placebo.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>The model was used for predicting population average and 90% 2-sided bootstrapped CI of the baseline-adjusted difference between active and placebo at each time point bound at clinically relevant concentrations.</non_inferiority_desc>
            <p_value>0.4727</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>-0.0077</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0255</ci_lower_limit>
            <ci_upper_limit>0.0101</ci_upper_limit>
            <estimate_desc>The primary mixed effects model analysis revealed a nearly flat dQTcF - plasma concentration gradient</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Concentrations of Moxidectin in Plasma</title>
        <description>Concentrations of moxidectin in plasma were assessed by collection of plasma samples at pre-specified intervals after oral dosing with moxidectin. The concentration of moxidectin was determined using a validated LC MS/MS method.The pharmacokinetic time points coincided with ECG collection timepoints (within 5 minutes and no later than 10 minutes after ECG recordings). Plasma PK parameters were estimated from the concentration measurements, including maximum concentration (Cmax) for each individual and mean for each dose cohort.</description>
        <time_frame>Pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12*, 24, 36, 48, 60, and 72 hours and days 8,15 and 22 post dosing</time_frame>
        <population>Pharmacokinetic population - includes all subjects who received at least 1 dose of moxidectin and provide an adequate number of plasma samples for determination of PK parameters, analyzed according to drug received.</population>
        <group_list>
          <group group_id="O1">
            <title>Moxidectin 4mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 4mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O2">
            <title>Moxidectin 8mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 8mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O3">
            <title>Moxidectin 16mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 16mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O4">
            <title>Moxidectin 24mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 24mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O5">
            <title>Moxidectin 36mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 36mg&#xD;
Moxidectin</description>
          </group>
        </group_list>
        <measure>
          <title>Concentrations of Moxidectin in Plasma</title>
          <description>Concentrations of moxidectin in plasma were assessed by collection of plasma samples at pre-specified intervals after oral dosing with moxidectin. The concentration of moxidectin was determined using a validated LC MS/MS method.The pharmacokinetic time points coincided with ECG collection timepoints (within 5 minutes and no later than 10 minutes after ECG recordings). Plasma PK parameters were estimated from the concentration measurements, including maximum concentration (Cmax) for each individual and mean for each dose cohort.</description>
          <population>Pharmacokinetic population - includes all subjects who received at least 1 dose of moxidectin and provide an adequate number of plasma samples for determination of PK parameters, analyzed according to drug received.</population>
          <units>nanogram/milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="10"/>
                <count group_id="O5" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.2" spread="30.6"/>
                    <measurement group_id="O2" value="56.7" spread="20.8"/>
                    <measurement group_id="O3" value="133" spread="27.1"/>
                    <measurement group_id="O4" value="176" spread="18.7"/>
                    <measurement group_id="O5" value="247" spread="19.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Subjects With Categorical Changes From Baseline in 12-lead Electrocardiograms (ECGs)</title>
        <description>Changes from baseline in QTcF exceeding regulatory standard categorical limits (&gt; 30msec change or exceeding 450msec). Report applies to changes of 30msec - &lt;/= 60msec only</description>
        <time_frame>At Baseline and Days 1, 2, 3, 4, 22 and Week 12</time_frame>
        <population>Safety population - all who received at least one dose of study drug</population>
        <group_list>
          <group group_id="O1">
            <title>Moxidectin 4mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 4mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O2">
            <title>Moxidectin 8mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 8mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O3">
            <title>Moxidectin 16mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 16mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O4">
            <title>Moxidectin 24mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 24mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O5">
            <title>Moxidectin 36mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 36mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O6">
            <title>Placebo</title>
            <description>10 subjects will receive a single oral dose of placebo&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Subjects With Categorical Changes From Baseline in 12-lead Electrocardiograms (ECGs)</title>
          <description>Changes from baseline in QTcF exceeding regulatory standard categorical limits (&gt; 30msec change or exceeding 450msec). Report applies to changes of 30msec - &lt;/= 60msec only</description>
          <population>Safety population - all who received at least one dose of study drug</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="10"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change From Baseline in Heart Rate (HR) and Duration of Other Interval Parameters (PR and QRS)</title>
        <description>Changes from Baseline were assessed at each timepoint up to 72 hours post dose. Mean changes across the 72 hour assessment period for each parameter were calculated for each moxidectin group and the placebo group and for the population overall.</description>
        <time_frame>Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing</time_frame>
        <population>ECG population - all subjects who receive one dose of study drug and have at least one pair of pre-dose and post-dose QTc data, analyzed as randomized</population>
        <group_list>
          <group group_id="O1">
            <title>Moxidectin 4mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 4mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O2">
            <title>Moxidectin 8mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 8mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O3">
            <title>Moxidectin 16mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 16mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O4">
            <title>Moxidectin 24mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 24mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O5">
            <title>Moxidectin 36mg</title>
            <description>10 subjects will receive a single oral dose of moxidectin 36mg&#xD;
Moxidectin</description>
          </group>
          <group group_id="O6">
            <title>Placebo</title>
            <description>10 subjects will receive a single oral dose of placebo&#xD;
Placebo</description>
          </group>
          <group group_id="O7">
            <title>All Subjects</title>
            <description>50 subjects received a single dose of moxidectin between 4mg and 36mg and 10 subjects received placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Heart Rate (HR) and Duration of Other Interval Parameters (PR and QRS)</title>
          <description>Changes from Baseline were assessed at each timepoint up to 72 hours post dose. Mean changes across the 72 hour assessment period for each parameter were calculated for each moxidectin group and the placebo group and for the population overall.</description>
          <population>ECG population - all subjects who receive one dose of study drug and have at least one pair of pre-dose and post-dose QTc data, analyzed as randomized</population>
          <units>milliseconds</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="10"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="10"/>
                <count group_id="O7" value="60"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change in Heart rate (HR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-4.80" upper_limit="2.76"/>
                    <measurement group_id="O2" value="0.5" lower_limit="-2.79" upper_limit="3.85"/>
                    <measurement group_id="O3" value="-1.1" lower_limit="-6.35" upper_limit="4.07"/>
                    <measurement group_id="O4" value="-3.6" lower_limit="-10.93" upper_limit="3.65"/>
                    <measurement group_id="O5" value="-1.5" lower_limit="-7.34" upper_limit="4.42"/>
                    <measurement group_id="O6" value="-2.9" lower_limit="-6.21" upper_limit="0.39"/>
                    <measurement group_id="O7" value="-0.005" lower_limit="-0.018" upper_limit="0.009"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change in PR interval</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" lower_limit="-0.49" upper_limit="4.87"/>
                    <measurement group_id="O2" value="-0.1" lower_limit="-5.84" upper_limit="5.66"/>
                    <measurement group_id="O3" value="-2.1" lower_limit="-7.63" upper_limit="3.47"/>
                    <measurement group_id="O4" value="4.6" lower_limit="-3.10" upper_limit="12.34"/>
                    <measurement group_id="O5" value="-3.5" lower_limit="-8.86" upper_limit="1.92"/>
                    <measurement group_id="O6" value="-1.8" lower_limit="-5.64" upper_limit="1.98"/>
                    <measurement group_id="O7" value="-0.002" lower_limit="-0.016" upper_limit="0.012"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change in QRS interval</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.6" lower_limit="-3.26" upper_limit="0.10"/>
                    <measurement group_id="O2" value="-0.7" lower_limit="-5.38" upper_limit="3.94"/>
                    <measurement group_id="O3" value="0.4" lower_limit="-1.75" upper_limit="2.49"/>
                    <measurement group_id="O4" value="-0.8" lower_limit="-3.55" upper_limit="2.03"/>
                    <measurement group_id="O5" value="0.4" lower_limit="-2.00" upper_limit="2.86"/>
                    <measurement group_id="O6" value="1.2" lower_limit="-0.29" upper_limit="2.59"/>
                    <measurement group_id="O7" value="0.004" lower_limit="-0.003" upper_limit="0.012"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected over the full 12 weeks of study follow-up</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Moxidectin 4mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 4mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="E2">
          <title>Moxidectin 8mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 8mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="E3">
          <title>Moxidectin 16mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 16mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="E4">
          <title>Moxidectin 24mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 24mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="E5">
          <title>Moxidectin 36mg</title>
          <description>10 subjects will receive a single oral dose of moxidectin 36mg&#xD;
Moxidectin</description>
        </group>
        <group group_id="E6">
          <title>Placebo</title>
          <description>10 subjects will receive a single oral dose of placebo&#xD;
Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <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="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (19.1)</default_vocab>
        <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="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye irritation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Medical device site reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>AST increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood cholesterol increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>
    <point_of_contact>
      <name_or_title>Sally Kinrade, Vice President (Clinical Development)</name_or_title>
      <organization>Medicines Development Limited</organization>
      <phone>+613 9629 6111</phone>
      <email>sally.kinrade@medicinesdevelopment.com</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/NCT03012828
org study id: MDGH-MOX-1008
nct id: NCT03012828
lead sponsor: 
has dmc: No
This study will investigate the effect of a single oral dose of moxidectin on the QT interval
      associated with moxidectin plasma concentrations.

      The effect of moxidectin on other ECG intervals, and on safety, will also be assessed, as
      will preliminary pharmacokinetics and metabolism
Moxidectin is being developed as a treatment for Onchocerciasis (river blindness), a serious,
      debilitating, disease caused by a parasitic worm, Onchocerca volvulus.

      Five dose levels of moxidectin will be administered to healthy volunteers and ECG assessments
      undertaken at pre-specified pharmacokinetic time points to correlate QT interval with
      moxidectin concentration in plasma.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean Change From Baseline in QTc Interval (Corrected by Friderica's Formula, dQTcF) Associated With Plasma Moxidectin Concentrations After a Single Dose
time frame: Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing
description: Triplicate 10-second ECG recordings taken 1 minute apart using a Mortara continuous 12-lead digital ECG recorder connected to each subject during the Baseline to 72-hour post dose confinement period. Baseline only and baseline and placebo adjusted changes in QTc interval (corrected using the Friderica formula, QTcF) at each timepoint for each dose level were determined. The mean change from baseline (without and with placebo correction, dQTcF and ddQTcF respectively) at each of the 14 time points was calculated for each dose level. The primary outcome measure was the mean dQTcF for all subjects(the dQTcF gradient). The mean dQTcF for each active treatment group was determined at each post dose timepoint but the mean dQTcF by dose level was not calculated. The mean dQTcF at approximate moxidectin Tmax (hour 3 or hour 4) for each active treatment group and at hour 3 for the placebo group is reported.
measure: Concentrations of Moxidectin in Plasma
time frame: Pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12*, 24, 36, 48, 60, and 72 hours and days 8,15 and 22 post dosing
description: Concentrations of moxidectin in plasma were assessed by collection of plasma samples at pre-specified intervals after oral dosing with moxidectin. The concentration of moxidectin was determined using a validated LC MS/MS method.The pharmacokinetic time points coincided with ECG collection timepoints (within 5 minutes and no later than 10 minutes after ECG recordings). Plasma PK parameters were estimated from the concentration measurements, including maximum concentration (Cmax) for each individual and mean for each dose cohort.
measure: Subjects With Categorical Changes From Baseline in 12-lead Electrocardiograms (ECGs)
time frame: At Baseline and Days 1, 2, 3, 4, 22 and Week 12
description: Changes from baseline in QTcF exceeding regulatory standard categorical limits (> 30msec change or exceeding 450msec). Report applies to changes of 30msec - </= 60msec only
measure: Change From Baseline in Heart Rate (HR) and Duration of Other Interval Parameters (PR and QRS)
time frame: Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing
description: Changes from Baseline were assessed at each timepoint up to 72 hours post dose. Mean changes across the 72 hour assessment period for each parameter were calculated for each moxidectin group and the placebo group and for the population overall.
arm group label: Moxidectin 4mg
arm group type: Experimental
description: 10 subjects will receive a single oral dose of moxidectin 4mg
arm group label: Moxidectin 8mg
arm group type: Experimental
description: 10 subjects will receive a single oral dose of moxidectin 8mg
arm group label: Moxidectin 16mg
arm group type: Experimental
description: 10 subjects will receive a single oral dose of moxidectin 16mg
arm group label: Moxidectin 24mg
arm group type: Experimental
description: 10 subjects will receive a single oral dose of moxidectin 24mg
arm group label: Moxidectin 36mg
arm group type: Experimental
description: 10 subjects will receive a single oral dose of moxidectin 36mg
arm group label: Placebo
arm group type: Placebo Comparator
description: 10 subjects will receive a single oral dose of placebo
intervention type: Drug
intervention name: Moxidectin
description: Moxidectin is a broad spectrum macrocyclic lactone endectocide
arm group label: Moxidectin 16mg
arm group label: Moxidectin 24mg
arm group label: Moxidectin 36mg
arm group label: Moxidectin 4mg
arm group label: Moxidectin 8mg
intervention type: Other
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mark Sullivan
role: Study Director
affiliation: Sponsor GmbH
facility: 
country: United States
responsible party type: Sponsor
mesh term: Moxidectin
sharing ipd: No
ipd description: Healthy volunteer study: results are not useful to individuals
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 