<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/NCT01713608</url>
  </required_header>
  <id_info>
    <org_study_id>MMV_OZ439_12_005</org_study_id>
    <secondary_id>2012-004187-22</secondary_id>
    <nct_id>NCT01713608</nct_id>
  </id_info>
  <brief_title>A Dose-escalation Study to Investigate Safety and Toleration of OZ439</brief_title>
  <official_title>A Randomised, Placebo-controlled, Dose-escalation Study to Investigate Safety and Toleration of OZ439 OD for 3 Days to Healthy Male and Female Volunteers</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>
      A randomised, placebo-controlled, dose-escalation study to investigate safety and toleration&#xD;
      of OZ439 OD for 3 days to healthy male and female volunteers. The study aims:&#xD;
&#xD;
        -  To determine the safety and tolerability of ascending doses of OZ439 OD for three days.&#xD;
&#xD;
        -  To assess pharmacokinetic parameters of ascending doses of OZ439 given OD.&#xD;
&#xD;
        -  To identify the maximum tolerated dose of OZ439 administered.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will be conducted in a randomised, placebo-controlled dose-escalation design with&#xD;
      OZ439 OD administered with full fat milk for three days to healthy male and female subjects&#xD;
      between 18 to 55 years of age, using features of an adaptive study design. The study is&#xD;
      expected to have three cohorts with a total of 36 healthy male and female subjects. An&#xD;
      additional two cohorts may be used if required. The results of this study will inform the&#xD;
      maximum tolerated exposure of OZ439 following OD dosing for three days in subjects who are&#xD;
      not fasted.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">February 2013</completion_date>
  <primary_completion_date type="Actual">February 2013</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>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>OZ439 Cmax</measure>
    <time_frame>Blood for analysis of OZ439 will be collected at the following times: pre-dose, 2, 4, 6, 8, 12, and 18 hours post-dose Day 1and Day 3, pre dose Day 2 and 4 hours post dose Day 2, and 24, 48, 72, 96 and 168 hours post 3rd dose and at follow up.</time_frame>
    <description>OZ439 maximum measured plasma concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>OZ439 AUCτ</measure>
    <time_frame>pre-dose, 2, 4, 6, 8, 12, and 18 hours post-dose Day 1and Day 3, pre dose Day 2 and 4 hours post dose Day 2, and 24, 48, 72, 96 and 168 hours post 3rd dose and at follow up.</time_frame>
    <description>OZ439 Area under the plasma concentration vs time curve from time zero to the time of the last quantifiable concentration t calculated using a log-linear trapezoidal method</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>OZ439 Tmax</measure>
    <time_frame>pre-dose, 2, 4, 6, 8, 12, and 18 hours post-dose Day 1and Day 3, pre dose Day 2 and 4 hours post dose Day 2, and 24, 48, 72, 96 and 168 hours post 3rd dose and at follow up.</time_frame>
    <description>Time to reach maximum measured OZ439 plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OZ439 t½</measure>
    <time_frame>pre-dose, 2, 4, 6, 8, 12, and 18 hours post-dose Day 1and Day 3, pre dose Day 2 and 4 hours post dose Day 2, and 24, 48, 72, 96 and 168 hours post 3rd dose and at follow up.</time_frame>
    <description>OZ439 estimated terminal phase half life</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Malaria</condition>
  <arm_group>
    <arm_group_label>OZ439 Dose level 1 (300mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>• Cohort 1 (12 subjects: 8 Active [A] and 4 on Placebo [P]) Active dose will consist of 300mg OZ439 drinking solution administered once daily for 3 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OZ439 Dose level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>• Cohort 2 (12 subjects: 8 A, 4P). Subjects on active will receive X amount of OZ439 (dose level to be determined based on safety and tolerability of previous dose level) drinking solution once daily for 3 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OZ439 dose level 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 3 (12 subjects: 8 A, 4P). Subjects on active will receive X amount of OZ439 (dose level to be determined based on safety and tolerability of previous dose level) drinking solution once daily for 3 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OZ439</intervention_name>
    <description>OZ439 x mg once daily for 3 days with milk</description>
    <arm_group_label>OZ439 Dose level 1 (300mg)</arm_group_label>
    <arm_group_label>OZ439 Dose level 2</arm_group_label>
    <arm_group_label>OZ439 dose level 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusions:&#xD;
&#xD;
          1. healthy males or females of any race aged 18 - 55 years&#xD;
&#xD;
          2. BMI of 18 - 30 kg/m2 inclusive at screening&#xD;
&#xD;
          3. Agree to use acceptable methods of contraception if of childbearing potential&#xD;
&#xD;
          4. Capable of understanding and complying with the requirements of the protocol and must&#xD;
             have signed the informed consent form&#xD;
&#xD;
          5. Females are either of child bearing potential or are confirmed as post-menopausal.&#xD;
             Post-menopausal is defined as being amenorrheic for 12 months without an alternative&#xD;
             medical cause with a screening FSH level ≥ 25.8 IU/L&#xD;
&#xD;
        Exclusions:&#xD;
&#xD;
          1. Male subjects with female partner(s) who is (are) pregnant or lactating from the time&#xD;
             of the first administration of study medication&#xD;
&#xD;
          2. Clinically significant disease or any condition or disease that might affect drug&#xD;
             absorption, distribution or excretion&#xD;
&#xD;
          3. History of allergic reactions to artemisinin-based compounds or any other clinically&#xD;
             relevant allergy to drugs or food&#xD;
&#xD;
          4. Clinically relevant history of both soya and cow's milk intolerance/allergy&#xD;
&#xD;
          5. Clinically significant abnormal laboratory, vital signs or other safety findings as&#xD;
             determined by medical history, physical examination or other evaluations conducted at&#xD;
             screening or on admission&#xD;
&#xD;
          6. Electrocardiogram (ECG) abnormalities in the standard 12-lead ECG (at screening)&#xD;
             and/or 24-hour 5 lead Holter ECG (at screening)&#xD;
&#xD;
          7. Any abnormalities in rhythm, conduction or morphology of resting ECG that may&#xD;
             interfere with the interpretation of QTc interval changes&#xD;
&#xD;
          8. Prolonged QTcF &gt;450 ms or shortened QTcF &lt;340 ms, or family history of Long QT&#xD;
             Syndrome&#xD;
&#xD;
          9. History or current evidence of any clinically relevant cardiovascular, pulmonary,&#xD;
             hepatic, renal, gastrointestinal, haematological, endocrinological, metabolic,&#xD;
             neurological, psychiatric, or other disease&#xD;
&#xD;
         10. Positive results in any of the serology tests for Hepatitis B Surface Antigen (HbsAg),&#xD;
             anti Hepatitis core antibody (anti HBc Ig G [and anti HBc IgM if IgG is positive],&#xD;
             Hepatitis C antibodies (anti HCV), and HIV 1 and 2 antibodies (anti HIV 1/2)&#xD;
&#xD;
         11. Confirmed positive results from urine drug screen (amphetamines, benzodiazepines,&#xD;
             cocaine, cannabinoids, opiates, barbiturates, and methadone) or from the alcohol&#xD;
             breath test at screening and on admission&#xD;
&#xD;
         12. History or clinical evidence of alcohol or drug abuse. Alcohol abuse is defined as&#xD;
             regular weekly intake of more than 21 units for males and 14 units for females; drug&#xD;
             abuse is defined as compulsive, repetitive and/or chronic use of drugs or other&#xD;
             substances with or without problems related to their use and/or where stopping or a&#xD;
             reduction in dose will lead to withdrawal symptoms&#xD;
&#xD;
         13. Is pregnant or lactating (female subjects who are of childbearing potential must have&#xD;
             negative pregnancy tests at screening and admission)&#xD;
&#xD;
         14. Mentally handicapped&#xD;
&#xD;
         15. Participation in a drug trial within 90 days prior to first drug administration&#xD;
&#xD;
         16. Use of any medication (incl. over-the-counter (OTC) medication) within 2 weeks prior&#xD;
             to drug administration (Day 1) or within less than 10 times the elimination half-life&#xD;
             of the respective drug, or anticipated concomitant medication during the treatment&#xD;
             periods, (whichever is longer), including herbal, traditional and alternative&#xD;
             medications. Excluding oral contraceptives (combination oestrogen/progesterone pills),&#xD;
             injectable progesterone or subdermal implants. Limited amounts (4g/day for 2 days) of&#xD;
             paracetamol will be permitted for the treatment of AEs&#xD;
&#xD;
         17. Treatment with herbal supplements during the 7 days prior to drug administration, or&#xD;
             use of vitamins during 48 hours prior to drug administration&#xD;
&#xD;
         18. Is not permitted to use strong inhibitors and/or inducers of CYP450 within 21 days&#xD;
             prior to the planned first drug administration&#xD;
&#xD;
         19. Subjects have veins unsuitable for intravenous puncture or cannulation on either arm&#xD;
             (e.g. veins that are difficult to locate, access or puncture veins with a tendency to&#xD;
             rupture during or after puncture)&#xD;
&#xD;
         20. Blood ALT, AST and bilirubin should be in the normal range at screening and on&#xD;
             admission&#xD;
&#xD;
         21. Donation of more than 500 mL of blood within 90 days prior to drug administration&#xD;
&#xD;
         22. Subjects must be non-smokers for at least three months prior to first drug&#xD;
             administration&#xD;
&#xD;
         23. Any circumstances or conditions, which, in the opinion of the PI, may affect full&#xD;
             participation in the trial or compliance with the protocol&#xD;
&#xD;
         24. Legal incapacity or limited legal capacity at screening&#xD;
&#xD;
         25. Subjects who are vegetarians, vegans or have any dietary restrictions conflicting with&#xD;
             the study standardised menus&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fiona Macintyre, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Medicines for Malaria Venture</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Richmond Pharmacology Ltd</name>
      <address>
        <city>Croydon</city>
        <zip>CR77YE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://mmv.org</url>
    <description>Company website</description>
  </link>
  <verification_date>March 2015</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>March 12, 2015</results_first_submitted>
  <results_first_submitted_qc>March 12, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">March 23, 2015</results_first_posted>
  <last_update_submitted>March 12, 2015</last_update_submitted>
  <last_update_submitted_qc>March 12, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 23, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>malaria</keyword>
  <keyword>dose escalation</keyword>
  <keyword>safety</keyword>
  <keyword>tolerability</keyword>
  <keyword>maximum tolerated dose</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>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>OZ439 300mg</title>
          <description>300mg OZ439 drinking solution administered once daily for 3 days with milk</description>
        </group>
        <group group_id="P2">
          <title>OZ439 600mg</title>
          <description>600mg OZ439 drinking solution administered once daily for 3 days with milk</description>
        </group>
        <group group_id="P3">
          <title>OZ439 700mg</title>
          <description>700mg OZ439 drinking solution administered once daily for 3 days with milk</description>
        </group>
        <group group_id="P4">
          <title>Placebo</title>
          <description>Placebo to match OZ439 PIB for 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="6"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>34 subjects were enrolled with all 34 completing the study.</population>
      <group_list>
        <group group_id="B1">
          <title>OZ439 300mg</title>
          <description>300mg OZ439 drinking solution administered once daily for 3 days with milk</description>
        </group>
        <group group_id="B2">
          <title>OZ439 600mg</title>
          <description>600mg OZ439 drinking solution administered once daily for 3 days with milk</description>
        </group>
        <group group_id="B3">
          <title>OZ439 700mg</title>
          <description>700mg OZ439 drinking solution administered once daily for 3 days with milk</description>
        </group>
        <group group_id="B4">
          <title>Placebo</title>
          <description>Placebo to match OZ439 PIB for oral suspension</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="8"/>
            <count group_id="B4" value="12"/>
            <count group_id="B5" value="34"/>
          </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="30.5" spread="8.91"/>
                    <measurement group_id="B2" value="25.5" spread="3.39"/>
                    <measurement group_id="B3" value="33.4" spread="8.09"/>
                    <measurement group_id="B4" value="30.5" spread="7.24"/>
                    <measurement group_id="B5" value="30.3" spread="7.51"/>
                  </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="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="15"/>
                  </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 Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23.1" spread="2.99"/>
                    <measurement group_id="B2" value="22.4" spread="3.29"/>
                    <measurement group_id="B3" value="24.4" spread="2.78"/>
                    <measurement group_id="B4" value="24.2" spread="3.02"/>
                    <measurement group_id="B5" value="23.7" spread="2.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>OZ439 Cmax</title>
        <description>OZ439 maximum measured plasma concentration</description>
        <time_frame>Blood for analysis of OZ439 will be collected at the following times: pre-dose, 2, 4, 6, 8, 12, and 18 hours post-dose Day 1and Day 3, pre dose Day 2 and 4 hours post dose Day 2, and 24, 48, 72, 96 and 168 hours post 3rd dose and at follow up.</time_frame>
        <population>PK Population: All subjects who received at least one dose of study medication and who had available evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>OZ439 300mg</title>
            <description>300mg OZ439 drinking solution administered once daily for 3 days with milk</description>
          </group>
          <group group_id="O2">
            <title>OZ439 600mg</title>
            <description>600mg OZ439 drinking solution administered once daily for 3 days with milk</description>
          </group>
          <group group_id="O3">
            <title>OZ439 700mg</title>
            <description>700mg OZ439 drinking solution administered once daily for 3 days with milk</description>
          </group>
        </group_list>
        <measure>
          <title>OZ439 Cmax</title>
          <description>OZ439 maximum measured plasma concentration</description>
          <population>PK Population: All subjects who received at least one dose of study medication and who had available evaluable PK data.</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="8"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="672" spread="183"/>
                    <measurement group_id="O2" value="1720" spread="544"/>
                    <measurement group_id="O3" value="1870" spread="600"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>OZ439 Tmax</title>
        <description>Time to reach maximum measured OZ439 plasma concentration</description>
        <time_frame>pre-dose, 2, 4, 6, 8, 12, and 18 hours post-dose Day 1and Day 3, pre dose Day 2 and 4 hours post dose Day 2, and 24, 48, 72, 96 and 168 hours post 3rd dose and at follow up.</time_frame>
        <population>PK Population: All subjects who received at least one dose of study medication and who had available evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>OZ439 300mg</title>
            <description>300mg OZ439 drinking solution administered once daily for 3 days with milk</description>
          </group>
          <group group_id="O2">
            <title>OZ439 600mg</title>
            <description>600mg OZ439 drinking solution administered once daily for 3 days with milk</description>
          </group>
          <group group_id="O3">
            <title>OZ439 700mg</title>
            <description>700mg OZ439 drinking solution administered once daily for 3 days with milk</description>
          </group>
        </group_list>
        <measure>
          <title>OZ439 Tmax</title>
          <description>Time to reach maximum measured OZ439 plasma concentration</description>
          <population>PK Population: All subjects who received at least one dose of study medication and who had available evaluable PK data.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.26" spread="1.04"/>
                    <measurement group_id="O2" value="3.67" spread="0.816"/>
                    <measurement group_id="O3" value="4.00" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>OZ439 AUCτ</title>
        <description>OZ439 Area under the plasma concentration vs time curve from time zero to the time of the last quantifiable concentration t calculated using a log-linear trapezoidal method</description>
        <time_frame>pre-dose, 2, 4, 6, 8, 12, and 18 hours post-dose Day 1and Day 3, pre dose Day 2 and 4 hours post dose Day 2, and 24, 48, 72, 96 and 168 hours post 3rd dose and at follow up.</time_frame>
        <population>PK Population: All subjects who received at least one dose of study medication and who had available evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>OZ439 300mg</title>
            <description>300mg OZ439 drinking solution administered once daily for 3 days with milk</description>
          </group>
          <group group_id="O2">
            <title>OZ439 600mg</title>
            <description>600mg OZ439 drinking solution administered once daily for 3 days with milk</description>
          </group>
          <group group_id="O3">
            <title>OZ439 700mg</title>
            <description>700mg OZ439 drinking solution administered once daily for 3 days with milk</description>
          </group>
        </group_list>
        <measure>
          <title>OZ439 AUCτ</title>
          <description>OZ439 Area under the plasma concentration vs time curve from time zero to the time of the last quantifiable concentration t calculated using a log-linear trapezoidal method</description>
          <population>PK Population: All subjects who received at least one dose of study medication and who had available evaluable PK data.</population>
          <units>ng*h/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="8"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5970" spread="1340"/>
                    <measurement group_id="O2" value="16500" spread="5630"/>
                    <measurement group_id="O3" value="21300" spread="6250"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>OZ439 t½</title>
        <description>OZ439 estimated terminal phase half life</description>
        <time_frame>pre-dose, 2, 4, 6, 8, 12, and 18 hours post-dose Day 1and Day 3, pre dose Day 2 and 4 hours post dose Day 2, and 24, 48, 72, 96 and 168 hours post 3rd dose and at follow up.</time_frame>
        <population>PK Population: All subjects who received at least one dose of study medication and who had available evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>OZ439 300mg</title>
            <description>300mg OZ439 drinking solution administered once daily for 3 days with milk</description>
          </group>
          <group group_id="O2">
            <title>OZ439 600mg</title>
            <description>600mg OZ439 drinking solution administered once daily for 3 days with milk</description>
          </group>
          <group group_id="O3">
            <title>OZ439 700mg</title>
            <description>700mg OZ439 drinking solution administered once daily for 3 days with milk</description>
          </group>
        </group_list>
        <measure>
          <title>OZ439 t½</title>
          <description>OZ439 estimated terminal phase half life</description>
          <population>PK Population: All subjects who received at least one dose of study medication and who had available evaluable PK data.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="122" spread="36.2"/>
                    <measurement group_id="O2" value="130" spread="21.8"/>
                    <measurement group_id="O3" value="134" spread="44.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <desc>The safety analysis included all 34 subjects who had received at least one treatment of randomised study medication and for whom any post-treatment data was available.</desc>
      <group_list>
        <group group_id="E1">
          <title>OZ439 300mg</title>
          <description>300mg OZ439 drinking solution administered once daily for 3 days with milk</description>
        </group>
        <group group_id="E2">
          <title>OZ439 600mg</title>
          <description>600mg OZ439 drinking solution administered once daily for 3 days with milk</description>
        </group>
        <group group_id="E3">
          <title>OZ439 700mg</title>
          <description>700mg OZ439 drinking solution administered once daily for 3 days with milk</description>
        </group>
        <group group_id="E4">
          <title>Placebo</title>
          <description>Placebo to match OZ439 PIB for 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="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (15.1)</default_vocab>
        <default_assessment>Non-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="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <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="6"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diarrhoea</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="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </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="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Migraine</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="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Somnolence</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="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Pregnancy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Rhinorrhoea</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="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</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="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </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>Dr Fiona Macintyre</name_or_title>
      <organization>Medicines for Malaria Venture</organization>
      <phone>+41 22 799 4078</phone>
      <email>macintyref@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/NCT01713608
org study id: MMV_OZ439_12_005
secondary id: 2012-004187-22
nct id: NCT01713608
lead sponsor: 
has dmc: No
A randomised, placebo-controlled, dose-escalation study to investigate safety and toleration
      of OZ439 OD for 3 days to healthy male and female volunteers. The study aims:

        -  To determine the safety and tolerability of ascending doses of OZ439 OD for three days.

        -  To assess pharmacokinetic parameters of ascending doses of OZ439 given OD.

        -  To identify the maximum tolerated dose of OZ439 administered.
This study will be conducted in a randomised, placebo-controlled dose-escalation design with
      OZ439 OD administered with full fat milk for three days to healthy male and female subjects
      between 18 to 55 years of age, using features of an adaptive study design. The study is
      expected to have three cohorts with a total of 36 healthy male and female subjects. An
      additional two cohorts may be used if required. The results of this study will inform the
      maximum tolerated exposure of OZ439 following OD dosing for three days in subjects who are
      not fasted.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: OZ439 Cmax
time frame: Blood for analysis of OZ439 will be collected at the following times: pre-dose, 2, 4, 6, 8, 12, and 18 hours post-dose Day 1and Day 3, pre dose Day 2 and 4 hours post dose Day 2, and 24, 48, 72, 96 and 168 hours post 3rd dose and at follow up.
description: OZ439 maximum measured plasma concentration
measure: OZ439 AUCτ
time frame: pre-dose, 2, 4, 6, 8, 12, and 18 hours post-dose Day 1and Day 3, pre dose Day 2 and 4 hours post dose Day 2, and 24, 48, 72, 96 and 168 hours post 3rd dose and at follow up.
description: OZ439 Area under the plasma concentration vs time curve from time zero to the time of the last quantifiable concentration t calculated using a log-linear trapezoidal method
measure: OZ439 Tmax
time frame: pre-dose, 2, 4, 6, 8, 12, and 18 hours post-dose Day 1and Day 3, pre dose Day 2 and 4 hours post dose Day 2, and 24, 48, 72, 96 and 168 hours post 3rd dose and at follow up.
description: Time to reach maximum measured OZ439 plasma concentration
measure: OZ439 t½
time frame: pre-dose, 2, 4, 6, 8, 12, and 18 hours post-dose Day 1and Day 3, pre dose Day 2 and 4 hours post dose Day 2, and 24, 48, 72, 96 and 168 hours post 3rd dose and at follow up.
description: OZ439 estimated terminal phase half life
arm group label: OZ439 Dose level 1 (300mg)
arm group type: Experimental
description: • Cohort 1 (12 subjects: 8 Active [A] and 4 on Placebo [P]) Active dose will consist of 300mg OZ439 drinking solution administered once daily for 3 days
arm group label: OZ439 Dose level 2
arm group type: Experimental
description: • Cohort 2 (12 subjects: 8 A, 4P). Subjects on active will receive X amount of OZ439 (dose level to be determined based on safety and tolerability of previous dose level) drinking solution once daily for 3 days
arm group label: OZ439 dose level 3
arm group type: Experimental
description: Cohort 3 (12 subjects: 8 A, 4P). Subjects on active will receive X amount of OZ439 (dose level to be determined based on safety and tolerability of previous dose level) drinking solution once daily for 3 days
intervention type: Drug
intervention name: OZ439
description: OZ439 x mg once daily for 3 days with milk
arm group label: OZ439 Dose level 1 (300mg)
arm group label: OZ439 Dose level 2
arm group label: OZ439 dose level 3
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Fiona Macintyre, PhD
role: Study Director
affiliation: Medicines for Malaria Venture
facility: 
country: United Kingdom
url: http://mmv.org
description: Company website
responsible party type: Sponsor
mesh term: Malaria
mesh term: Artefenomel
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 