<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/NCT01732588</url>
  </required_header>
  <id_info>
    <org_study_id>MMV_OZ439_12_003</org_study_id>
    <nct_id>NCT01732588</nct_id>
  </id_info>
  <brief_title>A Comparison of the Bioavailability of OZ439 When Delivered Directly to the Small Intestine, or Via the Oral Route</brief_title>
  <official_title>Three Way Randomised CrossOver Study in Healthy Subjects to Compare the Relative Bioavailability of Nanoparticulate OZ439 Delivered Via the Enterion™ Capsule to the Proximal Small Bowel With Orally Administered OZ439 as PIB Suspension and Orally Administered Nanoparticulate</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>
      The purpose of this study is to determine the bioavailability of nanoparticulate OZ439&#xD;
      delivered to the proximal small bowel (PSB) via the Enterion™ capsule relative to oral OZ439&#xD;
      suspension (current &quot;powder in bottle&quot; [PIB]) and oral nanoparticulate OZ439.&#xD;
&#xD;
      The study will also characterise the plasma concentration time profile of OZ439 when&#xD;
      delivered via Enterion capsule to the PSB in comparison with OZ439 PIB formulation delivered&#xD;
      orally and nanoparticulate OZ439 delivered orally Safety and tolerability of OZ439&#xD;
      formulations will be determined following delivery to the PSB and administered orally&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Previous clinical studies with OZ439 have shown variable PK and a food effect. One hypothesis&#xD;
      is that this may be related to a 'common ion effect' leading to precipitation of the drug as&#xD;
      a less soluble hydrochloride salt in the stomach, resulting in variable absorption of the&#xD;
      drug. This study is designed to investigate the possibility of improving the PK profile by&#xD;
      delivering the drug directly to the PSB, thereby bypassing the stomach. The study will&#xD;
      compare a previously dosed PIB formulation with oral delivery of a nanoparticulate as a&#xD;
      caplet formulation. The same caplet formulation containing nanoparticulate will be&#xD;
      administered to the PSB via the Enterion capsule.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">December 2012</completion_date>
  <primary_completion_date type="Actual">December 2012</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>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>OZ439 AUC0-∞</measure>
    <time_frame>pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose</time_frame>
    <description>Area under the plasma concentration-time curve from zero to infinity (AUC0-∞)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>OZ439 Cmax</measure>
    <time_frame>pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose</time_frame>
    <description>The maximum observed plasma drug concentrations (Cmax)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>OZ439 Tmax</measure>
    <time_frame>pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose</time_frame>
    <description>Time of maximum observed plasma drug concentrations (Tmax)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Regimen A - 120mg OZ439 PIB</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>120mg single dose of OZ439 as powder in bottle (PIB) formulation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regimen B - 120 mg OZ439 IR caplet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>120 mg single dose of OZ439 immediate release (IR) caplet formulation containing nanoparticulate, administered directly via the oral route</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regimen C - 120 mg OZ439 caplet via Enterion capsule</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>120 mg single dose of OZ439 caplet formulation containing nanoparticulate, administered orally via the Enterion capsule and delivered to the proximal small bowel</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OZ439 120mg PIB</intervention_name>
    <description>120mg dose (as free base) of OZ439 as a solution made up from powder in bottle (PIB)</description>
    <arm_group_label>Regimen A - 120mg OZ439 PIB</arm_group_label>
    <other_name>Regimen A</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>120 mg OZ439 caplet</intervention_name>
    <description>120 mg (as free base) of OZ439 immediate-release (IR) caplet formulation containing nanoparticulate, administered directly via the oral route</description>
    <arm_group_label>Regimen B - 120 mg OZ439 IR caplet</arm_group_label>
    <other_name>Regimen B</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>120mg OZ439 caplet via Enterion capsule</intervention_name>
    <description>120 mg OZ439 (as free base) in an immediate release (IR) caplet formulation containing nanoparticulate,administered orally via the Enterion capsule and delivered directly to the proximal small bowel (PSB)</description>
    <arm_group_label>Regimen C - 120 mg OZ439 caplet via Enterion capsule</arm_group_label>
    <other_name>Regimen C</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy males, or females of non-childbearing potential ie surgically sterilised or&#xD;
             post-menopausal&#xD;
&#xD;
          2. Age 18 to 55 years&#xD;
&#xD;
          3. Body mass index of 18 to 30 kg/m2 inclusive&#xD;
&#xD;
          4. Total body weight &gt;50 kg&#xD;
&#xD;
          5. Healthy as determined by pre-study medical history, physical examination (including&#xD;
             body temperature) and 12-lead ECG&#xD;
&#xD;
          6. Must have haematology, clinical chemistry and urinalysis results at screening that are&#xD;
             within the reference range or ncs&#xD;
&#xD;
          7. Must agree to use an adequate method of contraception&#xD;
&#xD;
          8. Must demonstrate their ability to swallow an empty size 000 capsule&#xD;
&#xD;
          9. Must be willing and able to communicate and participate in the whole study&#xD;
&#xD;
         10. Must provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Evidence or history of clinically significant oncological, pulmonary, chronic&#xD;
             respiratory, hepatic, cardiovascular, haematological, metabolic, neurological,&#xD;
             immunological, nephrological, endocrine or psychiatric disease, or current infection&#xD;
&#xD;
          2. Clinically relevant abnormalities in the ECG (12 standard leads) and/or QTcF &gt;450 ms&#xD;
             (males) or &gt;470 ms (females)&#xD;
&#xD;
          3. Evidence or history of clinically significant GI disease or surgery (excluding&#xD;
             appendectomy or cholecystectomy)&#xD;
&#xD;
          4. Any condition that could possibly affect drug absorption, eg gastrectomy or diarrhoea&#xD;
&#xD;
          5. History of post-antibiotic colitis&#xD;
&#xD;
          6. History of any drug or alcohol abuse in the past 2 years prior to screening&#xD;
&#xD;
          7. Subjects who have a breath carbon monoxide reading of greater than 10 ppm at&#xD;
             screening. Subjects who are tobacco users (including smokers and users of snuff,&#xD;
             chewing tobacco and other nicotine or nicotine-containing products) must have stopped&#xD;
             use within 90 days before screening&#xD;
&#xD;
          8. Receipt of an investigational drug or participation in another clinical research study&#xD;
             within the previous 3 months&#xD;
&#xD;
          9. Subjects who are study site employees, or immediate family members of a study site or&#xD;
             sponsor employee&#xD;
&#xD;
         10. Subjects who have previously been enrolled in this study&#xD;
&#xD;
         11. Use of any prescription or non-prescription medications, vitamins, herbal supplements&#xD;
             or dietary supplements within 14 days prior to the first dose&#xD;
&#xD;
         12. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab)or&#xD;
             human immunodeficiency virus (HIV-1 or HIV-2 antibody) results&#xD;
&#xD;
         13. Positive urine drug screen result&#xD;
&#xD;
         14. History of intolerance or hypersensitivity to artemisinins&#xD;
&#xD;
         15. Serious adverse reaction or serious hypersensitivity to any drug or the formulation&#xD;
             excipients&#xD;
&#xD;
         16. Presence or history of allergy requiring treatment; hayfever is allowed unless it is&#xD;
             active&#xD;
&#xD;
         17. Donation or loss of &gt;400 mL of blood within the previous 3 months&#xD;
&#xD;
         18. Haemoglobin result below the lower limit of the reference range&#xD;
&#xD;
         19. Regular alcohol consumption in males &gt;21 units per week and females &gt;14 units per week&#xD;
&#xD;
         20. Subjects who do not have suitable veins&#xD;
&#xD;
         21. Acute diarrhoea or constipation in the 7 days before the predicted first study day.&#xD;
&#xD;
         22. Presence of non-removable metal objects in the abdomen&#xD;
&#xD;
         23. Radiation exposure exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years&#xD;
&#xD;
         24. Failure to satisfy the investigator of fitness to participate for any other reason&#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>Quotient Clinical</name>
      <address>
        <city>Nottingham</city>
        <zip>NG11 6JS</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>February 2015</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 26, 2012</study_first_posted>
  <results_first_submitted>March 7, 2014</results_first_submitted>
  <results_first_submitted_qc>January 28, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 13, 2015</results_first_posted>
  <last_update_submitted>February 17, 2015</last_update_submitted>
  <last_update_submitted_qc>February 17, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 6, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bioavailability</keyword>
  <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>Sequence 1</title>
          <description>Subjects received a single dose of 120 mg OZ439 PIB oral suspension (Regimen A), then 120 mg OZ439 IR caplet (Regimen B); then 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C)</description>
        </group>
        <group group_id="P2">
          <title>Sequence 2</title>
          <description>Subjects received a single dose of 120 mg OZ439 IR caplet (Regimen B); then 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C); then 120 mg OZ439 PIB oral suspension (Regimen A).</description>
        </group>
        <group group_id="P3">
          <title>Sequence 3</title>
          <description>Subjects received a single dose of 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C); then 120 mg OZ439 PIB oral suspension (Regimen A); then 120 mg OZ439 IR caplet (Regimen B).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Intervention (7 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Second Intervention (7 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="4"/>
              </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_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Third Intervention (7 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="4"/>
              </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_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>cross over design so each regimen is represented in each sequence once</population>
      <group_list>
        <group group_id="B1">
          <title>Sequence 1</title>
          <description>Subjects received a single dose of 120 mg OZ439 PIB oral suspension (Regimen A), then 120 mg OZ439 IR caplet (Regimen B); then 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C)</description>
        </group>
        <group group_id="B2">
          <title>Sequence 2</title>
          <description>Subjects received a single dose of 120 mg OZ439 IR caplet (Regimen B); then 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C); then 120 mg OZ439 PIB oral suspension (Regimen A)</description>
        </group>
        <group group_id="B3">
          <title>Sequence 3</title>
          <description>Subjects received a single dose of 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule (Regimen C); then 120 mg OZ439 PIB oral suspension (Regimen A); then 120 mg OZ439 IR caplet (Regimen B).</description>
        </group>
        <group group_id="B4">
          <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="4"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="4"/>
            <count group_id="B4" value="11"/>
          </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="41.5" spread="12.0"/>
                    <measurement group_id="B2" value="35.3" spread="14.6"/>
                    <measurement group_id="B3" value="36.8" spread="12.3"/>
                    <measurement group_id="B4" value="38.1" spread="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="9"/>
                  </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="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.50" spread="3.7"/>
                    <measurement group_id="B2" value="24.67" spread="0.58"/>
                    <measurement group_id="B3" value="26.75" spread="1.89"/>
                    <measurement group_id="B4" value="26.09" spread="2.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="82.53" spread="13.44"/>
                    <measurement group_id="B2" value="68" spread="8.86"/>
                    <measurement group_id="B3" value="80.83" spread="1.44"/>
                    <measurement group_id="B4" value="77.95" spread="10.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>OZ439 AUC0-∞</title>
        <description>Area under the plasma concentration-time curve from zero to infinity (AUC0-∞)</description>
        <time_frame>pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose</time_frame>
        <population>PK population included all subjects who received at least 1 dose of IMP and who had sufficient plasma concentration data for PK parameter estimation.&#xD;
In addition, for Regimen C only subjects in whom the activation was performed successfully at the target site were included for this regimen.</population>
        <group_list>
          <group group_id="O1">
            <title>Regimen A - OZ439 120mg PIB</title>
            <description>Single dose of 120 mg OZ439 powder in bottle (PIB) oral suspension</description>
          </group>
          <group group_id="O2">
            <title>Regimen B - 120 mg OZ439 IR Caplet</title>
            <description>Single dose of 120 mg OZ439 Immediate release (IR) caplet formulation containing nanoparticulate</description>
          </group>
          <group group_id="O3">
            <title>Regimen C - 120 mg OZ439 Caplet Via Enterion Capsule</title>
            <description>Single dose of 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule</description>
          </group>
        </group_list>
        <measure>
          <title>OZ439 AUC0-∞</title>
          <description>Area under the plasma concentration-time curve from zero to infinity (AUC0-∞)</description>
          <population>PK population included all subjects who received at least 1 dose of IMP and who had sufficient plasma concentration data for PK parameter estimation.&#xD;
In addition, for Regimen C only subjects in whom the activation was performed successfully at the target site were included for this regimen.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1230" spread="46.5"/>
                    <measurement group_id="O2" value="907" spread="46.3"/>
                    <measurement group_id="O3" value="398" spread="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>OZ439 Cmax</title>
        <description>The maximum observed plasma drug concentrations (Cmax)</description>
        <time_frame>pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose</time_frame>
        <population>PK population included all subjects who received at least 1 dose of IMP and who had sufficient plasma concentration data for PK parameter estimation.&#xD;
In addition, for Regimen C only subjects in whom the activation was performed successfully at the target site were included for this regimen.</population>
        <group_list>
          <group group_id="O1">
            <title>Regimen A - OZ439 120mg PIB</title>
            <description>Single dose of 120 mg OZ439 powder in bottle (PIB) oral suspension</description>
          </group>
          <group group_id="O2">
            <title>Regimen B - 120 mg OZ439 IR Caplet</title>
            <description>Single dose of 120 mg OZ439 Immediate release (IR) caplet formulation containing nanoparticulate</description>
          </group>
          <group group_id="O3">
            <title>Regimen C - 120 mg OZ439 Caplet Via Enterion Capsule</title>
            <description>Single dose of 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule</description>
          </group>
        </group_list>
        <measure>
          <title>OZ439 Cmax</title>
          <description>The maximum observed plasma drug concentrations (Cmax)</description>
          <population>PK population included all subjects who received at least 1 dose of IMP and who had sufficient plasma concentration data for PK parameter estimation.&#xD;
In addition, for Regimen C only subjects in whom the activation was performed successfully at the target site were included for this regimen.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="180" spread="50.5"/>
                    <measurement group_id="O2" value="82.7" spread="73.5"/>
                    <measurement group_id="O3" value="35.4" spread="98.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>OZ439 Tmax</title>
        <description>Time of maximum observed plasma drug concentrations (Tmax)</description>
        <time_frame>pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose</time_frame>
        <population>PK population included all subjects who received at least 1 dose of IMP and who had sufficient plasma concentration data for PK parameter estimation.&#xD;
In addition, for Regimen C only subjects in whom the activation was performed successfully at the target site were included for this regimen.</population>
        <group_list>
          <group group_id="O1">
            <title>Regimen A - OZ439 120mg PIB</title>
            <description>Single dose of 120 mg OZ439 powder in bottle (PIB) oral suspension</description>
          </group>
          <group group_id="O2">
            <title>Regimen B - 120 mg OZ439 IR Caplet</title>
            <description>Single dose of 120 mg OZ439 Immediate release (IR) caplet formulation containing nanoparticulate</description>
          </group>
          <group group_id="O3">
            <title>Regimen C - 120 mg OZ439 Caplet Via Enterion Capsule</title>
            <description>Single dose of 120 mg OZ439 caplet formulation containing nanoparticulate delivered to the PSB via Enterion capsule</description>
          </group>
        </group_list>
        <measure>
          <title>OZ439 Tmax</title>
          <description>Time of maximum observed plasma drug concentrations (Tmax)</description>
          <population>PK population included all subjects who received at least 1 dose of IMP and who had sufficient plasma concentration data for PK parameter estimation.&#xD;
In addition, for Regimen C only subjects in whom the activation was performed successfully at the target site were included for this regimen.</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="9"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="2" upper_limit="4"/>
                    <measurement group_id="O2" value="4" lower_limit="2" upper_limit="6"/>
                    <measurement group_id="O3" value="4" lower_limit="2" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events collected from screening (up to 28 days) to follow up visit, ie up to 12 days after last OZ439 administration.</time_frame>
      <desc>The safety population was to include all subjects who have received at least 1 dose of IMP (ie, 11 subjects). In Sequence 2, one subject dropped out after the first intervention (Regimen B) and did not receive regimen A and C. Therefore the safety population for both regimens A and C includes 10 healthy subjects.</desc>
      <group_list>
        <group group_id="E1">
          <title>Regimen A - 120mg OZ439 PIB</title>
          <description>Single oral dose of 120 mg OZ439 as powder in bottle (PIB) formulation.</description>
        </group>
        <group group_id="E2">
          <title>Regimen B - 120 mg OZ439 IR Caplet</title>
          <description>Single oral dose of 120 mg OZ439 Immediate release (IR) caplet formulation containing nanoparticulate</description>
        </group>
        <group group_id="E3">
          <title>Regimen C - 120 mg OZ439 Caplet Via Enterion Capsule</title>
          <description>Single dose of 120 mg OZ439 caplet formulation containing nanoparticulate administered orally via the Enterion capsule</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="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (15.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>vessel puncture site haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>increased alanine aminotransferase</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>increased aspartate aminotransferase</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>abnormal electrocardiogram</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>abnormal urine analysis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </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="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr Fiona Macintyre</name_or_title>
      <organization>MMV</organization>
      <phone>+41 22 799 4060 ext 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/NCT01732588
org study id: MMV_OZ439_12_003
nct id: NCT01732588
lead sponsor: 
has dmc: No
The purpose of this study is to determine the bioavailability of nanoparticulate OZ439
      delivered to the proximal small bowel (PSB) via the Enterion™ capsule relative to oral OZ439
      suspension (current "powder in bottle" [PIB]) and oral nanoparticulate OZ439.

      The study will also characterise the plasma concentration time profile of OZ439 when
      delivered via Enterion capsule to the PSB in comparison with OZ439 PIB formulation delivered
      orally and nanoparticulate OZ439 delivered orally Safety and tolerability of OZ439
      formulations will be determined following delivery to the PSB and administered orally
Previous clinical studies with OZ439 have shown variable PK and a food effect. One hypothesis
      is that this may be related to a 'common ion effect' leading to precipitation of the drug as
      a less soluble hydrochloride salt in the stomach, resulting in variable absorption of the
      drug. This study is designed to investigate the possibility of improving the PK profile by
      delivering the drug directly to the PSB, thereby bypassing the stomach. The study will
      compare a previously dosed PIB formulation with oral delivery of a nanoparticulate as a
      caplet formulation. The same caplet formulation containing nanoparticulate will be
      administered to the PSB via the Enterion capsule.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: OZ439 AUC0-∞
time frame: pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose
description: Area under the plasma concentration-time curve from zero to infinity (AUC0-∞)
measure: OZ439 Cmax
time frame: pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose
description: The maximum observed plasma drug concentrations (Cmax)
measure: OZ439 Tmax
time frame: pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose
description: Time of maximum observed plasma drug concentrations (Tmax)
arm group label: Regimen A - 120mg OZ439 PIB
arm group type: Active Comparator
description: 120mg single dose of OZ439 as powder in bottle (PIB) formulation
arm group label: Regimen B - 120 mg OZ439 IR caplet
arm group type: Experimental
description: 120 mg single dose of OZ439 immediate release (IR) caplet formulation containing nanoparticulate, administered directly via the oral route
arm group label: Regimen C - 120 mg OZ439 caplet via Enterion capsule
arm group type: Experimental
description: 120 mg single dose of OZ439 caplet formulation containing nanoparticulate, administered orally via the Enterion capsule and delivered to the proximal small bowel
intervention type: Drug
intervention name: OZ439 120mg PIB
description: 120mg dose (as free base) of OZ439 as a solution made up from powder in bottle (PIB)
arm group label: Regimen A - 120mg OZ439 PIB
other name: Regimen A
intervention type: Drug
intervention name: 120 mg OZ439 caplet
description: 120 mg (as free base) of OZ439 immediate-release (IR) caplet formulation containing nanoparticulate, administered directly via the oral route
arm group label: Regimen B - 120 mg OZ439 IR caplet
other name: Regimen B
intervention type: Drug
intervention name: 120mg OZ439 caplet via Enterion capsule
description: 120 mg OZ439 (as free base) in an immediate release (IR) caplet formulation containing nanoparticulate,administered orally via the Enterion capsule and delivered directly to the proximal small bowel (PSB)
arm group label: Regimen C - 120 mg OZ439 caplet via Enterion capsule
other name: Regimen C
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: Artefenomel
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 