<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/NCT03261401</url>
  </required_header>
  <id_info>
    <org_study_id>MS201618_0013</org_study_id>
    <nct_id>NCT03261401</nct_id>
  </id_info>
  <brief_title>First-in-Human Trial of Single Ascending Dose, Multiple Ascending Dose and Malaria Challenge Model in Healthy Subjects</brief_title>
  <official_title>A Phase I, First-in-Human, Randomized, Double-Blind, Placebo-Controlled Trial of Single and Multiple Ascending Doses of M5717 to Assess the Safety, Tolerability and Pharmacokinetic Profile of Oral Doses, and to Assess the Antimalarial Activity of M5717 Against Plasmodium Falciparum in Healthy Male and Female Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck KGaA, Darmstadt, Germany</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck KGaA, Darmstadt, Germany</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary purpose of this study is to investigate the safety and tolerability of M5717 and&#xD;
      to characterize the Pharmacokinetics /Pharmacodynamic relationship between M5717 PK and&#xD;
      parasite clearance in healthy subjects following infection with Plasmodium falciparum.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 15, 2017</start_date>
  <completion_date type="Actual">June 14, 2019</completion_date>
  <primary_completion_date type="Actual">June 14, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part A and Part B: Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Day 1 up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A and Part B: Occurrence of Clinically Significant Changes and Abnormalities From Baseline in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings</measure>
    <time_frame>Day 1 up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Parasite Reduction Ratio (PRR) Assessed Through Quantitative Polymerase Chain Reaction (qPCR) Analysis</measure>
    <time_frame>Day 1 to Week 4 (Day 22)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Maximum Observed Blood Concentration (Cmax) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Time to Reach Maximum Blood Concentration of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Elimination Rate Constant (λz)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Apparent Terminal Half-Life (1/2)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Area Under the Concentration-Time Curve From Time Zero to 144 Hours (AUC0-144) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Area Under the Concentration-Time Curve From Time tlast Extrapolated to Infinity (AUCextra%) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Total Body Clearance (CL/f) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Apparent Volume of Distribution (Vz/f) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Dose Normalized Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Dose Normalized Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Dose Normalized Maximum Observed Blood Concentration (Cmax) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 10 nanogram per milliliter</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 3 nanogram per milliliter</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Accumulation ratio for AUC 0-24 of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Accumulation Ratio for Cmax of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero to Last Sampling Time (AUC 0-t,overall)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Area Under the Concentration-Time Curve Over Entire Dosing Time Period (From Time Zero Extrapolated to Infinity (AUC 0-inf,overall)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Average Blood Concentration at Steady State (Cav)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Minimum Observed Blood Concentration (Cmin)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part A: Maximum Observed Blood Concentration (Cmax) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Time to Reach Maximum Blood Concentration (tmax) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Apparent Terminal Half-Life (t1/2)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Area Under the Concentration-Time Curve From Time Zero to 144 Hours (AUC0-144) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Area Under the Concentration-Time Curve From Time tlast Extrapolated to Infinity (AUCextra%) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Total Body Clearance (CL/f) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Apparent Volume of Distribution (Vz/f) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Dose Normalized Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Dose Normalized Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Dose Normalized Maximum Observed Blood Concentration (Cmax) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 10 nanogram per milliliter</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 3 nanogram per milliliter</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Maximum Observed Blood Concentration (Cmax) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Time to Reach Maximum Blood Concentration (tmax) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Dose Normalized Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Dose Normalized Maximum Observed Blood Concentration (Cmax) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Area Under the Concentration-Time Curve From Time Zero to 144 Hours (AUC0-144) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Elimination Rate Constant (λz)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Apparent Terminal Half-Life (t1/2)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Accumulation Ratio for AUC 0-24 (R acc AUC) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Accumulation ratio for C max (R acc Cmax)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero to Last Sampling Time (AUC 0-t,overall)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Area Under the Concentration-Time Curve Over Entire Dosing Time Period (From Time Zero Extrapolated to Infinity (AUC 0-inf,overall)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 10 nanogram per milliliter</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 3 nanogram per milliliter</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Dose Normalized Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Area Under the Curve From Time tlast Extrapolated to Infinity Given as Percentage of AUC 0-infinity (AUC extra%)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Total Body Clearance (CL/f) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Apparent Volume of Distribution (Vz/f) of M5717</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Average Blood Concentration at Steady State (Cav)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Minimum Observed Blood Concentration (Cmin)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parasite Clearance Time</measure>
    <time_frame>Day 1 up to Week 4 (Day 22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimal Inhibitory Concentration</measure>
    <time_frame>Day 1 up to Week 4 (Day 22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lag Phase Assessed by Steady Exponential Decline in Parasite Count</measure>
    <time_frame>Day 1 up to Week 4 (Day 22)</time_frame>
    <description>Lag phase is defined as the time period (measured in hours) between administration of the test drug to a parasite infected subject until first sign of parasiticidal effect in terms of steady exponential decline in the parasite count.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With Recrudescence</measure>
    <time_frame>Day 1 up to Week 4 (Day 22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Malarial Clinical Score</measure>
    <time_frame>Day 1 up to Week 4 (Day 22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part C: Occurrence of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)</measure>
    <time_frame>Day 1 up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part C: Occurrence of TEAEs and SAEs by Severity</measure>
    <time_frame>Day 1 up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part C: Occurrence of Clinically Significant Changes and Abnormalities From Baseline in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings</measure>
    <time_frame>Day 1 up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Elimination Rate Constant (λz)</measure>
    <time_frame>Pre-dose up to end of trial visit (Week 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimal Parasiticidal Concentration (MPC)</measure>
    <time_frame>Day 1 up to Week 4 (Day 22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parasite Clearance Half-life (PCt½)</measure>
    <time_frame>Day 1 up to Week 4 (Day 22)</time_frame>
    <description>The parasite clearance half-life, defined as the time needed for parasitemia to be reduced by half during the log-linear phase of parasite clearance.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">112</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Part A: M5717</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: M5717</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part C: M5717</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>M5717</intervention_name>
    <description>Subjects will receive single ascending oral dose of M5717 after at least 8 hours of fasting together with water on Day 1, followed by a 4-hour post-dose fast</description>
    <arm_group_label>Part A: M5717</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>M5717</intervention_name>
    <description>Subjects will receive multiple ascending oral doses of M5717 after an overnight fast of at least 8 hours once daily for 3 days, followed by a 4-hour post-dose fast</description>
    <arm_group_label>Part B: M5717</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects will receive placebo matched to M5717</description>
    <arm_group_label>Part A: Placebo</arm_group_label>
    <arm_group_label>Part B: Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>M5717</intervention_name>
    <description>Subjects will receive single ascending oral dose of M5717 from Part A or as applicable multiple ascending oral doses of M5717 from Part B after at least 8 hours of fasting together with water on Day 1, followed by a 4-hour post-dose fast</description>
    <arm_group_label>Part C: M5717</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult men and women of non-childbearing potential, with total body weight greater than&#xD;
             or equal to 50.0 kilogram and body mass index (BMI) between 19.0 kilogram per meter&#xD;
             square(kg/m^2) and 29.9 kg/m^2.&#xD;
&#xD;
          -  Healthy as assessed by the Investigator with no clinically significant abnormality&#xD;
             identified on physical examination or laboratory evaluation and no active clinically&#xD;
             significant disorder, condition, infection or disease that would pose a risk to&#xD;
             subject safety or interfere with the trial evaluation, procedures, or completion.&#xD;
&#xD;
          -  Other protocol defined inclusion criteria could apply.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with history or presence of clinically relevant respiratory,&#xD;
             gastrointestinal, renal, hepatic, hematological, lymphatic, neurological,&#xD;
             cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological&#xD;
             dermatological, connective tissue diseases or disorders.&#xD;
&#xD;
          -  Subjects with history of relevant drug hypersensitivity, ascertained or presumptive&#xD;
             allergy/hypersensitivity to the active drug substance and/or formulation ingredients;&#xD;
             history of serious allergic reactions leading to hospitalization or any other allergic&#xD;
             reaction in general, which the Investigator considers may affect the safety of the&#xD;
             subject and/or outcome of the trial.&#xD;
&#xD;
          -  Subjects who have any history of malaria.&#xD;
&#xD;
          -  Subjects who have participated in a previous malaria vaccine trial.&#xD;
&#xD;
          -  Subjects who have participated in a previous human malaria challenge trial.&#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>Medical Responsible</last_name>
    <role>Study Director</role>
    <affiliation>Merck KGaA, Darmstadt, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Q-Pharm Pty Ltd</name>
      <address>
        <city>Brisbane</city>
        <zip>4006</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>August 18, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 25, 2017</study_first_posted>
  <last_update_submitted>June 18, 2019</last_update_submitted>
  <last_update_submitted_qc>June 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy Subjects</keyword>
  <keyword>M5717</keyword>
  <keyword>Malaria</keyword>
  <keyword>Plasmodium falciparum</keyword>
  <pending_results>
    <submitted>April 26, 2022</submitted>
    <submission_canceled>December 8, 2022</submission_canceled>
    <submitted>December 8, 2022</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03261401
org study id: MS201618_0013
nct id: NCT03261401
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary purpose of this study is to investigate the safety and tolerability of M5717 and
      to characterize the Pharmacokinetics /Pharmacodynamic relationship between M5717 PK and
      parasite clearance in healthy subjects following infection with Plasmodium falciparum.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Part A and Part B: Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
time frame: Day 1 up to end of trial visit (Week 7)
measure: Part A and Part B: Occurrence of Clinically Significant Changes and Abnormalities From Baseline in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings
time frame: Day 1 up to end of trial visit (Week 7)
measure: Part C: Parasite Reduction Ratio (PRR) Assessed Through Quantitative Polymerase Chain Reaction (qPCR) Analysis
time frame: Day 1 to Week 4 (Day 22)
measure: Part C: Maximum Observed Blood Concentration (Cmax) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Time to Reach Maximum Blood Concentration of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Elimination Rate Constant (λz)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Apparent Terminal Half-Life (1/2)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Area Under the Concentration-Time Curve From Time Zero to 144 Hours (AUC0-144) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Area Under the Concentration-Time Curve From Time tlast Extrapolated to Infinity (AUCextra%) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Total Body Clearance (CL/f) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Apparent Volume of Distribution (Vz/f) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Dose Normalized Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Dose Normalized Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Dose Normalized Maximum Observed Blood Concentration (Cmax) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 10 nanogram per milliliter
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 3 nanogram per milliliter
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Accumulation ratio for AUC 0-24 of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Accumulation Ratio for Cmax of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero to Last Sampling Time (AUC 0-t,overall)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Area Under the Concentration-Time Curve Over Entire Dosing Time Period (From Time Zero Extrapolated to Infinity (AUC 0-inf,overall)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Average Blood Concentration at Steady State (Cav)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part C: Minimum Observed Blood Concentration (Cmin)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Maximum Observed Blood Concentration (Cmax) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Time to Reach Maximum Blood Concentration (tmax) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Apparent Terminal Half-Life (t1/2)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Area Under the Concentration-Time Curve From Time Zero to 144 Hours (AUC0-144) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Area Under the Concentration-Time Curve From Time tlast Extrapolated to Infinity (AUCextra%) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Total Body Clearance (CL/f) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Apparent Volume of Distribution (Vz/f) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Dose Normalized Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Dose Normalized Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Dose Normalized Maximum Observed Blood Concentration (Cmax) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 10 nanogram per milliliter
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part A: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 3 nanogram per milliliter
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Maximum Observed Blood Concentration (Cmax) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Time to Reach Maximum Blood Concentration (tmax) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Dose Normalized Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Dose Normalized Maximum Observed Blood Concentration (Cmax) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Area Under the Concentration-Time Curve From Time Zero to 144 Hours (AUC0-144) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Elimination Rate Constant (λz)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Apparent Terminal Half-Life (t1/2)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Accumulation Ratio for AUC 0-24 (R acc AUC) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Accumulation ratio for C max (R acc Cmax)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero to Last Sampling Time (AUC 0-t,overall)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Area Under the Concentration-Time Curve Over Entire Dosing Time Period (From Time Zero Extrapolated to Infinity (AUC 0-inf,overall)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 10 nanogram per milliliter
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 3 nanogram per milliliter
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Dose Normalized Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Area Under the Curve From Time tlast Extrapolated to Infinity Given as Percentage of AUC 0-infinity (AUC extra%)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Total Body Clearance (CL/f) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Apparent Volume of Distribution (Vz/f) of M5717
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Average Blood Concentration at Steady State (Cav)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Part B: Minimum Observed Blood Concentration (Cmin)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Parasite Clearance Time
time frame: Day 1 up to Week 4 (Day 22)
measure: Minimal Inhibitory Concentration
time frame: Day 1 up to Week 4 (Day 22)
measure: Lag Phase Assessed by Steady Exponential Decline in Parasite Count
time frame: Day 1 up to Week 4 (Day 22)
description: Lag phase is defined as the time period (measured in hours) between administration of the test drug to a parasite infected subject until first sign of parasiticidal effect in terms of steady exponential decline in the parasite count.
measure: Number of Subjects With Recrudescence
time frame: Day 1 up to Week 4 (Day 22)
measure: Malarial Clinical Score
time frame: Day 1 up to Week 4 (Day 22)
measure: Part C: Occurrence of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)
time frame: Day 1 up to end of trial visit (Week 7)
measure: Part C: Occurrence of TEAEs and SAEs by Severity
time frame: Day 1 up to end of trial visit (Week 7)
measure: Part C: Occurrence of Clinically Significant Changes and Abnormalities From Baseline in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings
time frame: Day 1 up to end of trial visit (Week 7)
measure: Part A: Elimination Rate Constant (λz)
time frame: Pre-dose up to end of trial visit (Week 7)
measure: Minimal Parasiticidal Concentration (MPC)
time frame: Day 1 up to Week 4 (Day 22)
measure: Parasite Clearance Half-life (PCt½)
time frame: Day 1 up to Week 4 (Day 22)
description: The parasite clearance half-life, defined as the time needed for parasitemia to be reduced by half during the log-linear phase of parasite clearance.
arm group label: Part A: M5717
arm group type: Experimental
arm group label: Part A: Placebo
arm group type: Placebo Comparator
arm group label: Part B: M5717
arm group type: Experimental
arm group label: Part B: Placebo
arm group type: Placebo Comparator
arm group label: Part C: M5717
arm group type: Experimental
intervention type: Drug
intervention name: M5717
description: Subjects will receive single ascending oral dose of M5717 after at least 8 hours of fasting together with water on Day 1, followed by a 4-hour post-dose fast
arm group label: Part A: M5717
intervention type: Drug
intervention name: M5717
description: Subjects will receive multiple ascending oral doses of M5717 after an overnight fast of at least 8 hours once daily for 3 days, followed by a 4-hour post-dose fast
arm group label: Part B: M5717
intervention type: Drug
intervention name: Placebo
description: Subjects will receive placebo matched to M5717
arm group label: Part A: Placebo
arm group label: Part B: Placebo
intervention type: Drug
intervention name: M5717
description: Subjects will receive single ascending oral dose of M5717 from Part A or as applicable multiple ascending oral doses of M5717 from Part B after at least 8 hours of fasting together with water on Day 1, followed by a 4-hour post-dose fast
arm group label: Part C: M5717
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Responsible
role: Study Director
affiliation: Merck KGaA, Darmstadt, Germany
facility: 
country: Australia
responsible party type: Sponsor
submitted: April 26, 2022
submission canceled: December 8, 2022
submitted: December 8, 2022