<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/NCT01713621</url>
  </required_header>
  <id_info>
    <org_study_id>MMV_OZ439_12_006</org_study_id>
    <nct_id>NCT01713621</nct_id>
  </id_info>
  <brief_title>OZ439 PhIIa Study in Plasmodium Falciparum: Extended Observation</brief_title>
  <official_title>The Extended Observation Over a Period of 28 Days of the Effects of Single Doses of OZ439 on the Recrudescence of Plasmodium Falciparum Malaria - a PhIIa, Open Label Study in Adult Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medicines for Malaria Venture</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medicines for Malaria Venture</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to investigate the concentration dependent effects of OZ439 on the clearance&#xD;
      of P. falciparum parasites in patients, specifically the determination of an in-vivo minimum&#xD;
      inhibitory concentration (MIC) of OZ439. Characterisation of PK-PD&#xD;
      (Pharmacokinetic-Pharmacodynamic) relationships is essential for rational evidence based&#xD;
      dosing. The adaptive investigation of a range of doses will provide the best chance of&#xD;
      accurate PK-PD characterisation, allowing the observation of Plasmodium falciparum growth&#xD;
      dynamics and the subsequent identification of MIC and MPC (minimum parasiticidal&#xD;
      concentration). Additionally the tolerability and pharmacokinetics of OZ439 will be&#xD;
      confirmed. The PK/PD relationship between OZ439 exposure and subsequent effects on&#xD;
      parasitaemia will be investigated.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Minimum Inhibitory Concentration (MIC) and Minimum Parasiticidal Concentration (MPC)</measure>
    <time_frame>up to 28 days</time_frame>
    <description>The estimated MIC and MPC were derived from the fitted parasitaemia concentration and PK/PD relationship.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Malaria</condition>
  <arm_group>
    <arm_group_label>OZ439 100mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of 100mg of OZ439 administered as an oral suspension</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OZ439 500mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of 500mg of OZ439 administered as an oral suspension</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OZ439</intervention_name>
    <description>OZ439 is a novel synthetic trioxolane antimalarial agent</description>
    <arm_group_label>OZ439 100mg</arm_group_label>
    <arm_group_label>OZ439 500mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patients between the age of 18 and 60 years, inclusive&#xD;
&#xD;
          2. Body weight between 45 kg and 90 kg inclusive&#xD;
&#xD;
          3. Presence of mono-infection of P. falciparum confirmed by:&#xD;
&#xD;
               1. Fever, as defined by axillary temperature ≥ 37.5°C or oral/rectal/tympanic&#xD;
                  temperature ≥ 38°C, or history of fever in the previous 24 hours (history of&#xD;
                  fever must be documented) and,&#xD;
&#xD;
               2. Microscopically confirmed parasite infection: 1,000 to 75,000 asexual parasite&#xD;
                  count/µL blood.&#xD;
&#xD;
          4. Written informed consent, in accordance with local practice, provided by patient. If&#xD;
             the patient is unable to write, witnessed consent is permitted according to local&#xD;
             ethical considerations&#xD;
&#xD;
          5. Ability to swallow oral medication&#xD;
&#xD;
          6. Ability and willingness to participate and access the health facility&#xD;
&#xD;
          7. Agree to hospitalization for at least 72h until parasites have fallen below the level&#xD;
             of polymerase chain reaction (PCR) detection and have no signs or symptoms of malaria;&#xD;
             and then to return once daily to the study centre for blood sampling for quantitative&#xD;
             polymerase chain reaction (qPCR), and rehospitalisation when qPCR levels are&#xD;
             detectable.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with signs and symptoms of severe/complicated malaria requiring parenteral&#xD;
             treatment according to the World Health Organization Criteria 2010&#xD;
&#xD;
          2. Mixed Plasmodium infection&#xD;
&#xD;
          3. Severe vomiting, defined as more than three times in the 24 hours prior to inclusion&#xD;
             in the study or inability to tolerate oral treatment, or severe diarrhoea defined as 3&#xD;
             or more watery stools per day&#xD;
&#xD;
          4. Presence of other serious or chronic clinical condition requiring hospitalization&#xD;
&#xD;
          5. Severe malnutrition (defined as the weight-for-height being below -3 standard&#xD;
             deviation or less than 70% of median of the NCHS/WHO normalized reference values)&#xD;
&#xD;
          6. Known history or evidence of clinically significant disorders such as cardiovascular&#xD;
             (including arrhythmia, QTc interval greater than or equal to 450 msec), respiratory&#xD;
             (including active tuberculosis), history of jaundice, hepatic, renal,&#xD;
             gastrointestinal, immunological (including active HIV-AIDS), neurological (including&#xD;
             auditory), endocrine, infectious, malignancy, psychiatric, history of convulsions or&#xD;
             other abnormality (including head trauma)&#xD;
&#xD;
          7. Known history of hypersensitivity, allergic or adverse reactions to artemisinin&#xD;
             containing compounds or mefloquine&#xD;
&#xD;
          8. Known active Hepatitis A Immunoglobulin M (IgM) (HAV-IgM), Hepatitis B surface antigen&#xD;
             (HBsAg) or Hepatitis C antibody (HCV Ab)&#xD;
&#xD;
          9. Have received any antimalarial treatment in the preceding 14 days, as determined by&#xD;
             history and screening test&#xD;
&#xD;
         10. Have received antibacterial with known antimalarial activity in the preceding 14 days&#xD;
&#xD;
         11. Have received an investigational drug within the past 4 weeks&#xD;
&#xD;
         12. Liver function tests (Aspartate Aminotransferase(ASAT)/Alanine Aminotransferase (ALAT)&#xD;
             levels) &gt; 2x upper limit of normal (ULN) if Total Bilirubin normal or &gt;1.5xULN if&#xD;
             Total bilirubin between &gt;1 and &gt;1.5xULN&#xD;
&#xD;
         13. Hemoglobin (Hb) level =&lt; 8g/dl&#xD;
&#xD;
         14. Total Bilirubin &gt; 1.5XULN&#xD;
&#xD;
         15. Serum creatinine levels more than 2 times the upper limit of normal range (&gt;2xULN).&#xD;
&#xD;
         16. Female patients must be neither pregnant as demonstrated by a negative serum pregnancy&#xD;
             test at screening and urinary pregnancy test pre-dose (the result of the pre-dose&#xD;
             assessment must be confirmed negative prior to dosing) nor lactating, and must be&#xD;
             willing to take measures not to become pregnant during the study period and safety&#xD;
             follow-up period.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sasithon Pukrittayakamee, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Faculty of Tropical Medicine, Mahidol University, Bangkok</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Francois Nosten, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shoklo Malaria Research Unit, Faculty of Tropical medicine, Mahidol University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mae Ramat District hospital</name>
      <address>
        <city>Mae Ramat</city>
        <state>Tak</state>
        <zip>63140</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shoklo Malaria Research Unit</name>
      <address>
        <city>Mae Sot</city>
        <state>Tak</state>
        <zip>63110</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Faculty of Tropical Medicine,</name>
      <address>
        <city>Bangkok</city>
        <zip>10400</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <link>
    <url>http://mmv.org</url>
    <description>Information about Medicines for Malaria Venture</description>
  </link>
  <reference>
    <citation>Vennerstrom JL, Arbe-Barnes S, Brun R, Charman SA, Chiu FC, Chollet J, Dong Y, Dorn A, Hunziker D, Matile H, McIntosh K, Padmanilayam M, Santo Tomas J, Scheurer C, Scorneaux B, Tang Y, Urwyler H, Wittlin S, Charman WN. Identification of an antimalarial synthetic trioxolane drug development candidate. Nature. 2004 Aug 19;430(7002):900-4. doi: 10.1038/nature02779.</citation>
    <PMID>15318224</PMID>
  </reference>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 25, 2012</study_first_posted>
  <results_first_submitted>December 19, 2016</results_first_submitted>
  <results_first_submitted_qc>December 19, 2016</results_first_submitted_qc>
  <results_first_posted type="Actual">February 10, 2017</results_first_posted>
  <last_update_submitted>March 17, 2017</last_update_submitted>
  <last_update_submitted_qc>March 17, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>P. falciparum</keyword>
  <keyword>malaria</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Artefenomel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Patients were recruited and followed up over 28 days in four clinics in Thailand from April 2013 to April 2015.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>OZ439 100mg</title>
          <description>Single dose of 100mg of OZ439 administered as an oral suspension</description>
        </group>
        <group group_id="P2">
          <title>OZ439 500mg</title>
          <description>Single dose of 500mg of OZ439 administered as an oral suspension</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Analysed:&#xD;
Safety population: 25 patients Intent to Treat population: 23 patients Per Protocol population: 22 patients&#xD;
Pharmacokinetic (PK) population:&#xD;
Noncompartmental PK Analysis:19 patients Population PK Analysis: 22 patients</population>
      <group_list>
        <group group_id="B1">
          <title>OZ439 100mg</title>
          <description>Single dose of 100mg of OZ439 administered as an oral suspension</description>
        </group>
        <group group_id="B2">
          <title>OZ439 500mg</title>
          <description>Single dose of 500mg of OZ439 administered as an oral suspension</description>
        </group>
        <group group_id="B3">
          <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="8"/>
            <count group_id="B2" value="17"/>
            <count group_id="B3" value="25"/>
          </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" spread="12.44"/>
                    <measurement group_id="B2" value="34" spread="10.49"/>
                    <measurement group_id="B3" value="35" spread="10.98"/>
                  </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="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="25"/>
                  </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>Thailand</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Minimum Inhibitory Concentration (MIC) and Minimum Parasiticidal Concentration (MPC)</title>
        <description>The estimated MIC and MPC were derived from the fitted parasitaemia concentration and PK/PD relationship.</description>
        <time_frame>up to 28 days</time_frame>
        <population>Model predicted MIC and MPC</population>
        <group_list>
          <group group_id="O1">
            <title>OZ439 100mg</title>
            <description>Single dose of 100mg of OZ439 administered as an oral suspension</description>
          </group>
          <group group_id="O2">
            <title>OZ439 500mg</title>
            <description>Single dose of 500mg of OZ439 administered as an oral suspension</description>
          </group>
        </group_list>
        <measure>
          <title>Minimum Inhibitory Concentration (MIC) and Minimum Parasiticidal Concentration (MPC)</title>
          <description>The estimated MIC and MPC were derived from the fitted parasitaemia concentration and PK/PD relationship.</description>
          <population>Model predicted MIC and MPC</population>
          <units>ng/Ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Model predicted MIC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" spread="3.5"/>
                    <measurement group_id="O2" value="4.1" spread="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Model predicted MPC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77" spread="128"/>
                    <measurement group_id="O2" value="319" spread="877"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Patients were assessed for AEs for the duration of the study during the extended observation period, until study discontinuation and the follow-up visit.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>OZ439 100mg</title>
          <description>Single dose of 100mg of OZ439 administered as an oral suspension</description>
        </group>
        <group group_id="E2">
          <title>OZ439 500mg</title>
          <description>Single dose of 500mg of OZ439 administered as an oral suspension</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA</default_vocab>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>ANAEMIA</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>LEUKOPENIA</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>NEUTROPENIA</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>PALPITATIONS</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>PYREXIA</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ALANINE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>ASPARTATE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>BILIRUBIN CONJUGATED INCREASED</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>BLOOD BILIRUBIN INCREASED</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>HAEMOGLOBIN DECREASED</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>PLATELET COUNT DECREASED</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERGLYCAEMIA</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>DECREASED APPETITE</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>HYPOKALAEMIA</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>INSOMNIA</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>SLEEP DISORDER</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>LEUKOCYTURIA</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>EPISTAXIS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>PRURITUS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>RASH</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>RASH MACULO-PAPULAR</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>THROMBOPHLEBITIS</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Jörg J. Möhrle</name_or_title>
      <organization>Medicines for Malaria Venture</organization>
      <phone>+41 22 555 03 00</phone>
      <email>moehrlej@mmv.org</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/NCT01713621
org study id: MMV_OZ439_12_006
nct id: NCT01713621
lead sponsor: 
has dmc: No
This study aims to investigate the concentration dependent effects of OZ439 on the clearance
      of P. falciparum parasites in patients, specifically the determination of an in-vivo minimum
      inhibitory concentration (MIC) of OZ439. Characterisation of PK-PD
      (Pharmacokinetic-Pharmacodynamic) relationships is essential for rational evidence based
      dosing. The adaptive investigation of a range of doses will provide the best chance of
      accurate PK-PD characterisation, allowing the observation of Plasmodium falciparum growth
      dynamics and the subsequent identification of MIC and MPC (minimum parasiticidal
      concentration). Additionally the tolerability and pharmacokinetics of OZ439 will be
      confirmed. The PK/PD relationship between OZ439 exposure and subsequent effects on
      parasitaemia will be investigated.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Minimum Inhibitory Concentration (MIC) and Minimum Parasiticidal Concentration (MPC)
time frame: up to 28 days
description: The estimated MIC and MPC were derived from the fitted parasitaemia concentration and PK/PD relationship.
arm group label: OZ439 100mg
arm group type: Experimental
description: Single dose of 100mg of OZ439 administered as an oral suspension
arm group label: OZ439 500mg
arm group type: Experimental
description: Single dose of 500mg of OZ439 administered as an oral suspension
intervention type: Drug
intervention name: OZ439
description: OZ439 is a novel synthetic trioxolane antimalarial agent
arm group label: OZ439 100mg
arm group label: OZ439 500mg
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Sasithon Pukrittayakamee, MD
role: Principal Investigator
affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok
last name: Francois Nosten, MD
role: Principal Investigator
affiliation: Shoklo Malaria Research Unit, Faculty of Tropical medicine, Mahidol University
facility: 
facility: 
facility: 
country: Thailand
url: http://mmv.org
description: Information about Medicines for Malaria Venture
citation: Vennerstrom JL, Arbe-Barnes S, Brun R, Charman SA, Chiu FC, Chollet J, Dong Y, Dorn A, Hunziker D, Matile H, McIntosh K, Padmanilayam M, Santo Tomas J, Scheurer C, Scorneaux B, Tang Y, Urwyler H, Wittlin S, Charman WN. Identification of an antimalarial synthetic trioxolane drug development candidate. Nature. 2004 Aug 19;430(7002):900-4. doi: 10.1038/nature02779.
PMID: 15318224
responsible party type: Sponsor
mesh term: Malaria
mesh term: Artefenomel
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 