<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/NCT02230579</url>
  </required_header>
  <id_info>
    <org_study_id>MMV_MMV390048_14_01</org_study_id>
    <nct_id>NCT02230579</nct_id>
  </id_info>
  <brief_title>Phase I Study of Ascending Doses of MMV390048 in Healthy Adult Volunteers</brief_title>
  <official_title>A Single Centre, Two-part, Double-blind, Randomized, Placebo-controlled Phase I Study to Investigate the Safety, Tolerability, and Pharmacokinetic Profile of Ascending Doses of MMV390048 in Healthy Adult Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medicines for Malaria Venture</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Cape Town</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medicines for Malaria Venture</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a first-in-human study of MMV390048. The study will evaluate the safety, tolerability&#xD;
      and pharmacokinetic properties of escalating single and multiple doses of MMV390048 when&#xD;
      administered to healthy male volunteers and female volunteers of non-childbearing potential.&#xD;
&#xD;
      In addition, the effect of food on the pharmacokinetics and tolerability of MMV390048 will be&#xD;
      investigated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is a single centre, double-blind, randomised, placebo-controlled, ascending dose&#xD;
      study in healthy male and female volunteers (of non-childbearing potential) aged 18 to 55&#xD;
      years.&#xD;
&#xD;
      The study will be divided into two parts. The first part will comprise up to seven fasted&#xD;
      cohorts (8 to 10 volunteers in each) that will receive a single, ascending dose (SAD) of&#xD;
      MMV390048 to assess its safety, tolerability and pharmacokinetic profile. The starting dose&#xD;
      administered to the first cohort will be 5 mg. An additional cohort (cohort 8, re-using&#xD;
      volunteers from one of the previous cohorts) will receive a single dose of MMV390048 in a fed&#xD;
      state to evaluate the effect of food on the pharmacokinetics and tolerability of the&#xD;
      compound.&#xD;
&#xD;
      The data obtained from each cohort during the SAD part of the study will undergo a formal&#xD;
      review by the Safety Review Team (SRT). Should the safety profile of the compound be deemed&#xD;
      acceptable, and the pharmacokinetic parameters indicate that acceptable levels of the drug to&#xD;
      elicit a pharmacodynamic response can be achieved in human plasma, the study will then&#xD;
      proceed to the second part.&#xD;
&#xD;
      During the second part of the study volunteers will receive multiple, ascending doses (MAD)&#xD;
      of MMV390048 to assess the pharmacokinetics, safety and tolerability following multiple oral&#xD;
      doses. Up to three cohorts of eight volunteers each will be enrolled into this part of the&#xD;
      study. Each volunteer will receive three consecutive daily doses of MMV390048.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">February 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>up to D29 or longer according to half life</time_frame>
    <description>Subject will be in-house up to D3, and then have a follow up visit at the site on D5, 7, 10, 14, 19, 26, 29 or longer according to half life</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Versus Time Curve (AUC) of MMV390048</measure>
    <time_frame>0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose</time_frame>
    <description>Pk blood collection - additional PK point may be planned final visit depending on emerging PK data, unnecessary PK points could be eliminated for the latter cohorts Investigate the effect of food on the pharmacokinetic and tolerability of the investigational drug in cohort 4 and 8</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Half-life of MMV390048</measure>
    <time_frame>0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose</time_frame>
    <description>Pk blood collection Investigate the effect of food on the pharmacokinetic and tolerability of the investigational drug in cohort 4 and 8</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine ex Vivo Efficacy (IC50)</measure>
    <time_frame>up to 144 hr post dose</time_frame>
    <description>Blood collection to determine efficacy of investigational drug against parasites using an ex vivo malaria assay - this was done only for cohort 3 The experimentally obtained bioassay IC50 values were determined and compared to IC50 obtained with reference serum sample spiked with a known amount of MMV390048 titrated into the P. falciparum assay.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Malaria</condition>
  <arm_group>
    <arm_group_label>Cohort SAD1 Fasted</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort SAD2 Fasted</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort SAD3 Fasted</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort SAD4 Fasted</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort SAD5 Fasted</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort SAD6 Fed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort SAD6, reusing volunteers from one of the previous cohorts, will receive a single dose in a fed state to evaluate the effect of food on the pharmacokinetics and tolerability</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MMV390048 5mg</intervention_name>
    <description>Supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
    <arm_group_label>Cohort SAD1 Fasted</arm_group_label>
    <other_name>MMV390048</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MMV390048 20mg</intervention_name>
    <description>Supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose.</description>
    <arm_group_label>Cohort SAD2 Fasted</arm_group_label>
    <other_name>MMV390048</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MMV390048 40mg</intervention_name>
    <description>Supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
    <arm_group_label>Cohort SAD3 Fasted</arm_group_label>
    <arm_group_label>Cohort SAD6 Fed</arm_group_label>
    <other_name>MMV390048</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MMV390048 80mg</intervention_name>
    <description>Supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
    <arm_group_label>Cohort SAD4 Fasted</arm_group_label>
    <other_name>MMV390048</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MMV390048 120mg</intervention_name>
    <description>Supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
    <arm_group_label>Cohort SAD5 Fasted</arm_group_label>
    <other_name>MMV390048</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo to match MMV390048</intervention_name>
    <description>Supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
    <arm_group_label>Cohort SAD1 Fasted</arm_group_label>
    <arm_group_label>Cohort SAD2 Fasted</arm_group_label>
    <arm_group_label>Cohort SAD3 Fasted</arm_group_label>
    <arm_group_label>Cohort SAD4 Fasted</arm_group_label>
    <arm_group_label>Cohort SAD5 Fasted</arm_group_label>
    <arm_group_label>Cohort SAD6 Fed</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
          -  Male and female (of non-childbearing potential); age 18 to 55 years, in good health as&#xD;
             determined by past medical history, physical examination, vital signs,&#xD;
             electrocardiogram, and laboratory tests at screening&#xD;
&#xD;
          -  Hematology, clinical chemistry and urinalysis results at screening that are within the&#xD;
             local laboratory reference range or, if outside the range, not clinically significant.&#xD;
             AST, ALT, lactate dehydrogenase, total bilirubin, haptoglobin and hemoglobin must be&#xD;
             within the normal reference ranges&#xD;
&#xD;
          -  Body weight at least 50kg and body mass index within 18 to 32kg/m2&#xD;
&#xD;
          -  Good peripheral venous access&#xD;
&#xD;
          -  Able to communicate well with the investigator, to understand and comply with the&#xD;
             requirements of the study&#xD;
&#xD;
          -  Agree to stay in contact with the study site for the duration of the study, provide&#xD;
             updated contact information as necessary, and have no current plans to move away from&#xD;
             the study area for the duration of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any acute illness upon admission to the unit on Day -1 or prior to dosing on Day 1&#xD;
&#xD;
          -  Use of any other investigational drug within 30 days or five half-lives (whichever is&#xD;
             longer) prior to the first dose of MMV390048&#xD;
&#xD;
          -  history of hypersensitivity to any drugs&#xD;
&#xD;
          -  history of anaphylaxis or severe allergic reaction&#xD;
&#xD;
          -  Resting vital signs at either screening or baseline outside the defined ranges&#xD;
&#xD;
          -  Orthostatic changes in blood pressure and heart rate measurements greater than: 20&#xD;
             mmHg drop in systolic blood pressure; 10 mmHg drop in diastolic blood pressure; 20&#xD;
             beats per minute increase in heart rate&#xD;
&#xD;
          -  history of clinically significant ECG abnormalities, or any of the defined ECG&#xD;
             abnormalities at either screening or baseline&#xD;
&#xD;
          -  History of malignancy of any organ system (other than localized basal cell carcinoma&#xD;
             of the skin), treated or untreated, within the past five years, regardless of whether&#xD;
             there is evidence of local recurrence or metastases&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women&#xD;
&#xD;
          -  Women of child-bearing potential&#xD;
&#xD;
          -  males physiologically capable of conceiving offspring UNLESS the volunteer agrees to&#xD;
             use condoms and ensure that his partner(s) is either not of child-bearing potential or&#xD;
             uses a highly effective method of contraception for the entire duration of the study&#xD;
             and for twelve weeks following the last study drug administration&#xD;
&#xD;
          -  Smokers (use of tobacco products in the previous three months)&#xD;
&#xD;
          -  Use of any prescription drugs, herbal supplements, over--the--counter medication or&#xD;
             dietary supplements (vitamins included) within four weeks prior to initial dosing&#xD;
&#xD;
          -  Intake of grapefruit, grapefruit juice or other products containing grapefruit within&#xD;
             28 days of the first drug administration of the study drug&#xD;
&#xD;
          -  Excessive intake of caffeine drinks or energy drinks within 48 hours before admission&#xD;
             defined as more than three 250 ml cups of coffee a day&#xD;
&#xD;
          -  Donation or loss of 400 ml or more of blood within eight weeks prior to screening or&#xD;
             initial dosing&#xD;
&#xD;
          -  Plasma donation (&gt;100 ml) within 60 days prior to first dosing&#xD;
&#xD;
          -  Hemoglobin levels below 12.5 g/dl (males) or 11.5 g/dl (females) at screening&#xD;
&#xD;
          -  Haptoglobin levels outside the reference range&#xD;
&#xD;
          -  Positive direct anti-globulin test&#xD;
&#xD;
          -  Liver enzymes other than ALT, AST and lactate dehydrogenase elevated ≥1.5 x ULN within&#xD;
             two weeks prior to initial dosing&#xD;
&#xD;
          -  history of autonomic dysfunction within 3 years and/or recurrent history&#xD;
&#xD;
          -  History of immunodeficiency diseases, including a confirmed positive HIV test result&#xD;
&#xD;
          -  Positive Hepatitis B surface antigen or Hepatitis C antibody test result&#xD;
&#xD;
          -  History of recurrent infection&#xD;
&#xD;
          -  history of endocrine disease, in particular adrenal disorders such as Cushing's&#xD;
             syndrome or Addison's disease, or diabetes mellitus&#xD;
&#xD;
          -  history of Gilbert's Syndrome&#xD;
&#xD;
          -  history of photosensitivity&#xD;
&#xD;
          -  history of any food allergy&#xD;
&#xD;
          -  Any surgical or medical condition which might significantly alter the absorption,&#xD;
             distribution, metabolism, or excretion of drugs, or which may jeopardise the safety of&#xD;
             the volunteer or the objectives of the study&#xD;
&#xD;
          -  History or presence of impaired renal function as indicated by clinically&#xD;
             significantly abnormal creatinine or urea values, or abnormal urinary constituents&#xD;
&#xD;
          -  History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of&#xD;
             such abuse as indicated by the tests and laboratory assays at screening and/or&#xD;
             baseline&#xD;
&#xD;
          -  Any clinically significant mental disorder that could limit the validity of informed&#xD;
             consent or the volunteer's ability to comply with protocol requirements&#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>Karen Barnes, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cape Town</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cinical Pharmacology, University of Cape Town</name>
      <address>
        <city>Cape Town</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>August 29, 2014</study_first_submitted>
  <study_first_submitted_qc>August 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <results_first_submitted>November 2, 2016</results_first_submitted>
  <results_first_submitted_qc>February 1, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">October 29, 2018</results_first_posted>
  <last_update_submitted>July 16, 2019</last_update_submitted>
  <last_update_submitted_qc>July 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>safety</keyword>
  <keyword>tolerability</keyword>
  <keyword>malaria</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>For the purposes of this study, subjects that were re-used in SAD6 were treated as separate subjects, i.e. the entire trial population comprised 48 subjects, eight subjects in 6 cohorts.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort SAD1 Fasted</title>
          <description>5mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose&#xD;
Placebo: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="P2">
          <title>Cohort SAD2 Fasted</title>
          <description>20mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose&#xD;
Placebo: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="P3">
          <title>Cohort SAD3 Fasted</title>
          <description>40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose&#xD;
Placebo: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="P4">
          <title>Cohort SAD4 Fasted</title>
          <description>80mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose&#xD;
Placebo: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="P5">
          <title>Cohort SAD5 Fasted</title>
          <description>120mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose&#xD;
Placebo: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="P6">
          <title>Cohort SAD6 Fed</title>
          <description>Reusing volunteers from one of the previous cohorts, will receive a single dose in a fed state to evaluate the effect of food on the pharmacokinetics and tolerability.&#xD;
40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose&#xD;
Placebo: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="P7">
          <title>Placebo</title>
          <description>Placebo to match MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose Two volunteers within each cohort (SAD1 to SAD6) were scheduled to receive placebo in a double blind manner.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="6"/>
                <participants group_id="P7" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="6"/>
                <participants group_id="P7" 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 group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort SAD1 Fasted</title>
          <description>5mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="B2">
          <title>Cohort SAD2 Fasted</title>
          <description>20mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="B3">
          <title>Cohort SAD3 Fasted</title>
          <description>40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="B4">
          <title>Cohort SAD4 Fasted</title>
          <description>80mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="B5">
          <title>Cohort SAD5 Fasted</title>
          <description>120mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="B6">
          <title>Cohort SAD6 Fed</title>
          <description>Cohort SAD6, reusing volunteers from previous cohorts, will receive a single dose in a fed state to evaluate the effect of food on the pharmacokinetics and tolerability&#xD;
40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="B7">
          <title>Placebo</title>
          <description>Placebo to match MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose&#xD;
Two volunteers within each cohort (SAD1 to SAD6) were scheduled to receive placebo in a double blind manner.</description>
        </group>
        <group group_id="B8">
          <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="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="6"/>
            <count group_id="B6" value="6"/>
            <count group_id="B7" value="12"/>
            <count group_id="B8" value="48"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.3" lower_limit="19" upper_limit="44"/>
                    <measurement group_id="B2" value="34" lower_limit="24" upper_limit="51"/>
                    <measurement group_id="B3" value="37" lower_limit="29" upper_limit="49"/>
                    <measurement group_id="B4" value="30" lower_limit="21" upper_limit="51"/>
                    <measurement group_id="B5" value="23.7" lower_limit="19" upper_limit="30"/>
                    <measurement group_id="B6" value="34" lower_limit="20" upper_limit="50"/>
                    <measurement group_id="B7" value="32.7" lower_limit="19" upper_limit="50"/>
                    <measurement group_id="B8" value="31.7" lower_limit="19" upper_limit="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="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="1"/>
                    <measurement group_id="B8" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="4"/>
                    <measurement group_id="B7" value="11"/>
                    <measurement group_id="B8" value="40"/>
                  </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 group_id="B8" 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="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 group_id="B8" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</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="4"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="4"/>
                    <measurement group_id="B7" value="9"/>
                    <measurement group_id="B8" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</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="1"/>
                    <measurement group_id="B8" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="2"/>
                    <measurement group_id="B8" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>Subject will be in-house up to D3, and then have a follow up visit at the site on D5, 7, 10, 14, 19, 26, 29 or longer according to half life</description>
        <time_frame>up to D29 or longer according to half life</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort SAD1 Fasted</title>
            <description>5mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O2">
            <title>Cohort SAD2 Fasted</title>
            <description>20mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O3">
            <title>Cohort SAD3 Fasted</title>
            <description>40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O4">
            <title>Cohort SAD4 Fasted</title>
            <description>80mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O5">
            <title>Cohort SAD5 Fasted</title>
            <description>120mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O6">
            <title>Cohort SAD6 Fed</title>
            <description>Cohort SAD6, reusing volunteers from previous cohorts, will receive a single dose in a fed state to evaluate the effect of food on the pharmacokinetics and tolerability&#xD;
40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O7">
            <title>Placebo</title>
            <description>Placebo to match MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose&#xD;
Two volunteers within each cohort (SAD1 to SAD6) were scheduled to receive placebo in a double blind manner.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>Subject will be in-house up to D3, and then have a follow up visit at the site on D5, 7, 10, 14, 19, 26, 29 or longer according to half life</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="6"/>
                    <measurement group_id="O5" value="6"/>
                    <measurement group_id="O6" value="6"/>
                    <measurement group_id="O7" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Versus Time Curve (AUC) of MMV390048</title>
        <description>Pk blood collection - additional PK point may be planned final visit depending on emerging PK data, unnecessary PK points could be eliminated for the latter cohorts Investigate the effect of food on the pharmacokinetic and tolerability of the investigational drug in cohort 4 and 8</description>
        <time_frame>0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose</time_frame>
        <population>One subject (SAD5 120 mg) was excluded from the PK analysis population due to concomitant use of prohibited medications known to produce drug-drug interactions with pharmacokinetic consequences.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort SAD1 Fasted</title>
            <description>5mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O2">
            <title>Cohort SAD2 Fasted</title>
            <description>20mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O3">
            <title>Cohort SAD3 Fasted</title>
            <description>40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O4">
            <title>Cohort SAD4 Fasted</title>
            <description>80mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O5">
            <title>Cohort SAD5 Fasted</title>
            <description>120mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O6">
            <title>Cohort SAD6 Fed</title>
            <description>Cohort SAD6, reusing volunteers from previous cohorts, will receive a single dose in a fed state to evaluate the effect of food on the pharmacokinetics and tolerability&#xD;
40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Versus Time Curve (AUC) of MMV390048</title>
          <description>Pk blood collection - additional PK point may be planned final visit depending on emerging PK data, unnecessary PK points could be eliminated for the latter cohorts Investigate the effect of food on the pharmacokinetic and tolerability of the investigational drug in cohort 4 and 8</description>
          <population>One subject (SAD5 120 mg) was excluded from the PK analysis population due to concomitant use of prohibited medications known to produce drug-drug interactions with pharmacokinetic consequences.</population>
          <units>h*ng/mL</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2136.9" lower_limit="903.1" upper_limit="3718.7"/>
                    <measurement group_id="O2" value="32727.2" lower_limit="24895.2" upper_limit="38914.3"/>
                    <measurement group_id="O3" value="21050.7" lower_limit="6325.4" upper_limit="37934.6"/>
                    <measurement group_id="O4" value="58668.2" lower_limit="40246" upper_limit="125655.1"/>
                    <measurement group_id="O5" value="156036.2" lower_limit="13053" upper_limit="208989.4"/>
                    <measurement group_id="O6" value="29004.6" lower_limit="15775.1" upper_limit="72735.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Determine ex Vivo Efficacy (IC50)</title>
        <description>Blood collection to determine efficacy of investigational drug against parasites using an ex vivo malaria assay - this was done only for cohort 3 The experimentally obtained bioassay IC50 values were determined and compared to IC50 obtained with reference serum sample spiked with a known amount of MMV390048 titrated into the P. falciparum assay.</description>
        <time_frame>up to 144 hr post dose</time_frame>
        <population>Samples received from the remaining participants were not processed due to the fact that they were either placebo samples, or failed to reach the pre-determined in vitro IC50 of MMV390048.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort SAD1 Fasted</title>
            <description>5mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O2">
            <title>Cohort SAD2 Fasted</title>
            <description>20mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O3">
            <title>Cohort SAD3 Fasted</title>
            <description>40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O4">
            <title>Cohort SAD4 Fasted</title>
            <description>80mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O5">
            <title>Cohort SAD5 Fasted</title>
            <description>120mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O6">
            <title>Cohort SAD6 Fed</title>
            <description>Cohort SAD6, reusing volunteers from previous cohorts, will receive a single dose in a fed state to evaluate the effect of food on the pharmacokinetics and tolerability&#xD;
40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
        </group_list>
        <measure>
          <title>Determine ex Vivo Efficacy (IC50)</title>
          <description>Blood collection to determine efficacy of investigational drug against parasites using an ex vivo malaria assay - this was done only for cohort 3 The experimentally obtained bioassay IC50 values were determined and compared to IC50 obtained with reference serum sample spiked with a known amount of MMV390048 titrated into the P. falciparum assay.</description>
          <population>Samples received from the remaining participants were not processed due to the fact that they were either placebo samples, or failed to reach the pre-determined in vitro IC50 of MMV390048.</population>
          <units>ng/ml</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="0"/>
                <count group_id="O5" value="0"/>
                <count group_id="O6" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="9.475" lower_limit="9.1" upper_limit="9.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Half-life of MMV390048</title>
        <description>Pk blood collection Investigate the effect of food on the pharmacokinetic and tolerability of the investigational drug in cohort 4 and 8</description>
        <time_frame>0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose</time_frame>
        <population>One subject (SAD5 120 mg) was excluded from the PK analysis population due to concomitant use of prohibited medications known to produce drug-drug interactions with pharmacokinetic consequences.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort SAD1 Fasted</title>
            <description>5mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O2">
            <title>Cohort SAD2 Fasted</title>
            <description>20mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O3">
            <title>Cohort SAD3 Fasted</title>
            <description>40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O4">
            <title>Cohort SAD4 Fasted</title>
            <description>80mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O5">
            <title>Cohort SAD5 Fasted</title>
            <description>120mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
          <group group_id="O6">
            <title>Cohort SAD6 Fed</title>
            <description>Cohort SAD6, reusing volunteers from previous cohorts, will receive a single dose in a fed state to evaluate the effect of food on the pharmacokinetics and tolerability&#xD;
40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
          </group>
        </group_list>
        <measure>
          <title>Half-life of MMV390048</title>
          <description>Pk blood collection Investigate the effect of food on the pharmacokinetic and tolerability of the investigational drug in cohort 4 and 8</description>
          <population>One subject (SAD5 120 mg) was excluded from the PK analysis population due to concomitant use of prohibited medications known to produce drug-drug interactions with pharmacokinetic consequences.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="163.1" lower_limit="86.9" upper_limit="297.0"/>
                    <measurement group_id="O2" value="326.1" lower_limit="221.6" upper_limit="348.0"/>
                    <measurement group_id="O3" value="192.6" lower_limit="84.2" upper_limit="486.2"/>
                    <measurement group_id="O4" value="200.3" lower_limit="154.1" upper_limit="457.1"/>
                    <measurement group_id="O5" value="252.3" lower_limit="132.5" upper_limit="263.5"/>
                    <measurement group_id="O6" value="210.8" lower_limit="111.3" upper_limit="461.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Cohort SAD1 Fasted</title>
          <description>5mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="E2">
          <title>Cohort SAD2 Fasted</title>
          <description>20mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="E3">
          <title>Cohort SAD3 Fasted</title>
          <description>40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="E4">
          <title>Cohort SAD4 Fasted</title>
          <description>80mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="E5">
          <title>Cohort SAD5 Fasted</title>
          <description>120mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="E6">
          <title>Cohort SAD6 Fed</title>
          <description>Cohort SAD6, reusing volunteers from previous cohorts, will receive a single dose in a fed state to evaluate the effect of food on the pharmacokinetics and tolerability 40mg of MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose</description>
        </group>
        <group group_id="E7">
          <title>Placebo</title>
          <description>Placebo to match MMV390048: Single administration, supplied as &quot;powder in bottle&quot; formulation for reconstitution pre-dose Two volunteers within each cohort (SAD1 to SAD6) were scheduled to receive placebo in a double blind manner.</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="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>generalised myoclonus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="11" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood CK increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" 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" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Medical device site reaction</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Diziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Furuncle</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Thermal burn</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" 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 Cristina Donini - Associate Director</name_or_title>
      <organization>Medicines for Malaria Venture</organization>
      <phone>00 41 22 555 03 12</phone>
      <email>doninic@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/NCT02230579
org study id: MMV_MMV390048_14_01
nct id: NCT02230579
lead sponsor: 
collaborator: 
has dmc: Yes
This is a first-in-human study of MMV390048. The study will evaluate the safety, tolerability
      and pharmacokinetic properties of escalating single and multiple doses of MMV390048 when
      administered to healthy male volunteers and female volunteers of non-childbearing potential.

      In addition, the effect of food on the pharmacokinetics and tolerability of MMV390048 will be
      investigated.
The study is a single centre, double-blind, randomised, placebo-controlled, ascending dose
      study in healthy male and female volunteers (of non-childbearing potential) aged 18 to 55
      years.

      The study will be divided into two parts. The first part will comprise up to seven fasted
      cohorts (8 to 10 volunteers in each) that will receive a single, ascending dose (SAD) of
      MMV390048 to assess its safety, tolerability and pharmacokinetic profile. The starting dose
      administered to the first cohort will be 5 mg. An additional cohort (cohort 8, re-using
      volunteers from one of the previous cohorts) will receive a single dose of MMV390048 in a fed
      state to evaluate the effect of food on the pharmacokinetics and tolerability of the
      compound.

      The data obtained from each cohort during the SAD part of the study will undergo a formal
      review by the Safety Review Team (SRT). Should the safety profile of the compound be deemed
      acceptable, and the pharmacokinetic parameters indicate that acceptable levels of the drug to
      elicit a pharmacodynamic response can be achieved in human plasma, the study will then
      proceed to the second part.

      During the second part of the study volunteers will receive multiple, ascending doses (MAD)
      of MMV390048 to assess the pharmacokinetics, safety and tolerability following multiple oral
      doses. Up to three cohorts of eight volunteers each will be enrolled into this part of the
      study. Each volunteer will receive three consecutive daily doses of MMV390048.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants With Adverse Events
time frame: up to D29 or longer according to half life
description: Subject will be in-house up to D3, and then have a follow up visit at the site on D5, 7, 10, 14, 19, 26, 29 or longer according to half life
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of MMV390048
time frame: 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose
description: Pk blood collection - additional PK point may be planned final visit depending on emerging PK data, unnecessary PK points could be eliminated for the latter cohorts Investigate the effect of food on the pharmacokinetic and tolerability of the investigational drug in cohort 4 and 8
measure: Half-life of MMV390048
time frame: 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose
description: Pk blood collection Investigate the effect of food on the pharmacokinetic and tolerability of the investigational drug in cohort 4 and 8
measure: Determine ex Vivo Efficacy (IC50)
time frame: up to 144 hr post dose
description: Blood collection to determine efficacy of investigational drug against parasites using an ex vivo malaria assay - this was done only for cohort 3 The experimentally obtained bioassay IC50 values were determined and compared to IC50 obtained with reference serum sample spiked with a known amount of MMV390048 titrated into the P. falciparum assay.
arm group label: Cohort SAD1 Fasted
arm group type: Experimental
description: Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state
arm group label: Cohort SAD2 Fasted
arm group type: Experimental
description: Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state
arm group label: Cohort SAD3 Fasted
arm group type: Experimental
description: Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state
arm group label: Cohort SAD4 Fasted
arm group type: Experimental
description: Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state
arm group label: Cohort SAD5 Fasted
arm group type: Experimental
description: Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state
arm group label: Cohort SAD6 Fed
arm group type: Experimental
description: Cohort SAD6, reusing volunteers from one of the previous cohorts, will receive a single dose in a fed state to evaluate the effect of food on the pharmacokinetics and tolerability
intervention type: Drug
intervention name: MMV390048 5mg
description: Supplied as "powder in bottle" formulation for reconstitution pre-dose
arm group label: Cohort SAD1 Fasted
other name: MMV390048
intervention type: Drug
intervention name: MMV390048 20mg
description: Supplied as "powder in bottle" formulation for reconstitution pre-dose.
arm group label: Cohort SAD2 Fasted
other name: MMV390048
intervention type: Drug
intervention name: MMV390048 40mg
description: Supplied as "powder in bottle" formulation for reconstitution pre-dose
arm group label: Cohort SAD3 Fasted
arm group label: Cohort SAD6 Fed
other name: MMV390048
intervention type: Drug
intervention name: MMV390048 80mg
description: Supplied as "powder in bottle" formulation for reconstitution pre-dose
arm group label: Cohort SAD4 Fasted
other name: MMV390048
intervention type: Drug
intervention name: MMV390048 120mg
description: Supplied as "powder in bottle" formulation for reconstitution pre-dose
arm group label: Cohort SAD5 Fasted
other name: MMV390048
intervention type: Drug
intervention name: Placebo to match MMV390048
description: Supplied as "powder in bottle" formulation for reconstitution pre-dose
arm group label: Cohort SAD1 Fasted
arm group label: Cohort SAD2 Fasted
arm group label: Cohort SAD3 Fasted
arm group label: Cohort SAD4 Fasted
arm group label: Cohort SAD5 Fasted
arm group label: Cohort SAD6 Fed
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Karen Barnes, Prof
role: Principal Investigator
affiliation: University of Cape Town
facility: 
country: South Africa
responsible party type: Sponsor
mesh term: Malaria
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 