xml: <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/NCT06006559</url>
    </required_header>
    <id_info>
      <org_study_id>CEYU688A12201</org_study_id>
      <nct_id>NCT06006559</nct_id>
    </id_info>
    <brief_title>A Study to Assess the Efficacy, Safety and Pharmacokinetics of EYU688 in Patients With Dengue Fever</brief_title>
    <official_title>A Randomized, Participant- and Investigator-blinded, Placebo-controlled, Parallel Group Study to Assess the Efficacy, Safety and Pharmacokinetics of EYU688 in Patients With Dengue Fever</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Novartis Pharmaceuticals</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Novartis</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 purpose of this study is to characterize the effect on dengue viral load, fever clearance&#xD;
        time as well as on clinical signs and symptoms with the treatment of EYU688 compared with&#xD;
        placebo in patients with dengue fever.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a randomized, participant- and investigator- blinded, placebo-controlled study to&#xD;
        investigate the efficacy and safety of EYU688 administered orally in patients with dengue&#xD;
        fever.&#xD;
  &#xD;
        Due to the different PK sampling schedules applied, the study consists of two cohorts run in&#xD;
        parallel (intensive PK [cohort 1] and sparse PK sampling [cohort 2]).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 10, 2023</start_date>
    <completion_date type="Anticipated">December 2, 2024</completion_date>
    <primary_completion_date type="Anticipated">October 30, 2024</primary_completion_date>
    <phase>Phase 2</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>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Viremia reduction (viral load reduction (VLR) on log scale) at 48 hours post treatment start</measure>
      <time_frame>From predose to 48 hours post treatment start</time_frame>
      <description>Efficacy assessment of EYU688. It will allow to quantify the viremia reduction at 48 hours post treatment start from baseline.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Time from fever onset to start of the first 48 hours period during which the oral temperature remained below 37.5℃</measure>
      <time_frame>From fever onset to Day 15</time_frame>
      <description>Efficacy assessment of EYU688. It will allow to assess the time needed between fever onset and defervescence.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time from fever onset to the first of two consecutive negative viremia by PCR</measure>
      <time_frame>From fever onset to Day 15</time_frame>
      <description>Efficacy assessment will allow to assess the viremia kinetic from treatment start to Day15</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the log-transformed viremia curve (AUC) from the first dose to Day 15</measure>
      <time_frame>From fever onset to Day 15</time_frame>
      <description>Efficacy assessment will allow to assess the viremia kinetic from treatment start to Day 15</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of viral load over time</measure>
      <time_frame>From baseline to Day 15</time_frame>
      <description>Efficacy assessment will allow to assess the viremia kinetic from treatment start to Day15</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence and severity of Adverse Events (AEs)</measure>
      <time_frame>From inclusion to Day 15</time_frame>
      <description>Incidence and severity of AEs by treatment group, including changes in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence and severity of Serious Adverse Events (SAEs)</measure>
      <time_frame>From inclusion to Day 35</time_frame>
      <description>Incidence and severity of SAEs by treatment group</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change of white blood cell count over time from baseline</measure>
      <time_frame>From baseline to Day 15</time_frame>
      <description>Assessment of safety and tolerability of EYU688</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change of platelet count over time</measure>
      <time_frame>From baseline to Day 15</time_frame>
      <description>Assessment of safety and tolerability of EYU688</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change of hematocrit level and percentage increase from baseline over time</measure>
      <time_frame>From baseline to Day 15</time_frame>
      <description>Assessment of safety and tolerability of EYU688</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change of AST, ALT levels over time</measure>
      <time_frame>From baseline to Day 15</time_frame>
      <description>Assessment of safety and tolerability of EYU688</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>No warning signs by day 7 of fever onset</measure>
      <time_frame>From inclusion to Day 15</time_frame>
      <description>Assessment of the dengue fever clinical evolution under EYU688</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diagnosis of severe dengue fever</measure>
      <time_frame>From inclusion to Day 15</time_frame>
      <description>Assessment of the dengue fever clinical evolution under EYU688</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diagnosis of dengue hemorrhagic fever (DHF)</measure>
      <time_frame>From inclusion to Day 15</time_frame>
      <description>Assessment of the dengue fever clinical evolution under EYU688</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma leakage</measure>
      <time_frame>From inclusion to Day 15</time_frame>
      <description>Assessment of the dengue fever clinical evolution under EYU688</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Requiring fluid infusion</measure>
      <time_frame>From inclusion to Day 15</time_frame>
      <description>Assessment of the dengue fever clinical evolution under EYU688</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time from fever onset to clinical recovery</measure>
      <time_frame>From fever onset to Day 15</time_frame>
      <description>Assessment of the dengue fever clinical evolution under EYU688</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK parameter (Cmax)</measure>
      <time_frame>From Day 1 to Day 6</time_frame>
      <description>Pharmacokinetic assessment of EYU688 in dengue fever patients</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK parameter (Tmax)</measure>
      <time_frame>From Day 1 to Day 6</time_frame>
      <description>Pharmacokinetic assessment of EYU688 in dengue fever patients</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK parameter (partial AUCs)</measure>
      <time_frame>From Day 1 to Day 6</time_frame>
      <description>Pharmacokinetic assessment of EYU688 in dengue fever patients</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK concentrations following multiple doses</measure>
      <time_frame>From Day 1 to Day 6</time_frame>
      <description>Pharmacokinetic assessment of EYU688 in dengue fever patients</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">108</enrollment>
    <condition>Dengue</condition>
    <arm_group>
      <arm_group_label>EYU688</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>EYU688 administered by oral route</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Matching placebo</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>EYU688</intervention_name>
      <description>EYU688 administered by oral route</description>
      <arm_group_label>EYU688</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Matching placebo administered orally as capsules</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male or female, 18 - 60 years old (inclusive).&#xD;
  &#xD;
            -  History or presence of fever (≥ 38°C). At least one of the following criteria&#xD;
               indicating dengue infection:&#xD;
  &#xD;
            -  Nausea or vomiting.&#xD;
  &#xD;
            -  Presence of rash, aches or pains including headache, muscle or joint pain.&#xD;
  &#xD;
            -  Onset of fever ≤ 48 hours prior to treatment start.&#xD;
  &#xD;
            -  Positive test on dengue fever.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Participants with any of abnormalities of clinical laboratory parameters.&#xD;
  &#xD;
            -  Usage of any anticoagulant drugs.&#xD;
  &#xD;
            -  Current significant medical conditions or illness that the investigator considers&#xD;
               should exclude the participants, especially those that require continuation of other&#xD;
               medications likely to have an interaction with the study drug.&#xD;
  &#xD;
            -  Pregnant or nursing (lactating) women.&#xD;
  &#xD;
            -  Clinical signs and symptoms for severe dengue according to Dengue Guideline (WHO 2009)&#xD;
               at screening.&#xD;
  &#xD;
            -  Participants with any of the following abnormalities of clinical laboratory parameters&#xD;
               at screening:&#xD;
  &#xD;
                 -  Hemoglobin &lt;12.0 g/dL in males; &lt;11.0 g/dL in females&#xD;
  &#xD;
                 -  Hematocrit &gt;52 % in males; &gt;46 % in females&#xD;
  &#xD;
                 -  Absolute neutrophil count &lt;1500/μL&#xD;
  &#xD;
                 -  Platelet count &lt;80,000/mm3&#xD;
  &#xD;
                 -  Creatinine &gt;165 μmol/L in males; &gt;130 μmol/L in females&#xD;
  &#xD;
                 -  Serum creatine kinase &gt; 600 U/L&#xD;
  &#xD;
                 -  ALT, AST levels more than 1.5X upper limit of normal (ULN)&#xD;
  &#xD;
                 -  Total bilirubin &gt;24 μmol/L&#xD;
  &#xD;
            -  Usage of PPIs (proton pump inhibitor) which could affect absorption of EYU688 due to&#xD;
               stomach pH value increase up to 48 hours prior to screening.&#xD;
  &#xD;
            -  Women of child-bearing potential, defined as all women physiologically capable of&#xD;
               becoming pregnant, unless they are using highly effective methods of contraception&#xD;
               during dosing and for five half-lives or 4 days whichever is longer after stopping of&#xD;
               investigational drug.&#xD;
  &#xD;
            -  History or long-QT syndrome, or clinically significant ECG abnormalities, or any of&#xD;
               the following ECG abnormalities at screening:&#xD;
  &#xD;
                 -  QTcF &gt; 450 msec (males)&#xD;
  &#xD;
                 -  QTcF &gt; 460 msec (females)&#xD;
  &#xD;
          Other protocol-defined inclusion/exclusion criteria may apply.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Novartis Pharmaceuticals</last_name>
      <phone>+41613241111</phone>
      <email>novartis.email@novartis.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Novartis Pharmaceuticals</last_name>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Dengue</keyword>
    <keyword>EYU688</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Dengue</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06006559
  org study id: CEYU688A12201
  nct id: NCT06006559
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this study is to characterize the effect on dengue viral load, fever clearance
        time as well as on clinical signs and symptoms with the treatment of EYU688 compared with
        placebo in patients with dengue fever.
  This is a randomized, participant- and investigator- blinded, placebo-controlled study to
        investigate the efficacy and safety of EYU688 administered orally in patients with dengue
        fever.
  
        Due to the different PK sampling schedules applied, the study consists of two cohorts run in
        parallel (intensive PK [cohort 1] and sparse PK sampling [cohort 2]).
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Viremia reduction (viral load reduction (VLR) on log scale) at 48 hours post treatment start
  time frame: From predose to 48 hours post treatment start
  description: Efficacy assessment of EYU688. It will allow to quantify the viremia reduction at 48 hours post treatment start from baseline.
  measure: Time from fever onset to start of the first 48 hours period during which the oral temperature remained below 37.5℃
  time frame: From fever onset to Day 15
  description: Efficacy assessment of EYU688. It will allow to assess the time needed between fever onset and defervescence.
  measure: Time from fever onset to the first of two consecutive negative viremia by PCR
  time frame: From fever onset to Day 15
  description: Efficacy assessment will allow to assess the viremia kinetic from treatment start to Day15
  measure: Area under the log-transformed viremia curve (AUC) from the first dose to Day 15
  time frame: From fever onset to Day 15
  description: Efficacy assessment will allow to assess the viremia kinetic from treatment start to Day 15
  measure: Changes of viral load over time
  time frame: From baseline to Day 15
  description: Efficacy assessment will allow to assess the viremia kinetic from treatment start to Day15
  measure: Incidence and severity of Adverse Events (AEs)
  time frame: From inclusion to Day 15
  description: Incidence and severity of AEs by treatment group, including changes in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs.
  measure: Incidence and severity of Serious Adverse Events (SAEs)
  time frame: From inclusion to Day 35
  description: Incidence and severity of SAEs by treatment group
  measure: Change of white blood cell count over time from baseline
  time frame: From baseline to Day 15
  description: Assessment of safety and tolerability of EYU688
  measure: Change of platelet count over time
  time frame: From baseline to Day 15
  description: Assessment of safety and tolerability of EYU688
  measure: Change of hematocrit level and percentage increase from baseline over time
  time frame: From baseline to Day 15
  description: Assessment of safety and tolerability of EYU688
  measure: Change of AST, ALT levels over time
  time frame: From baseline to Day 15
  description: Assessment of safety and tolerability of EYU688
  measure: No warning signs by day 7 of fever onset
  time frame: From inclusion to Day 15
  description: Assessment of the dengue fever clinical evolution under EYU688
  measure: Diagnosis of severe dengue fever
  time frame: From inclusion to Day 15
  description: Assessment of the dengue fever clinical evolution under EYU688
  measure: Diagnosis of dengue hemorrhagic fever (DHF)
  time frame: From inclusion to Day 15
  description: Assessment of the dengue fever clinical evolution under EYU688
  measure: Plasma leakage
  time frame: From inclusion to Day 15
  description: Assessment of the dengue fever clinical evolution under EYU688
  measure: Requiring fluid infusion
  time frame: From inclusion to Day 15
  description: Assessment of the dengue fever clinical evolution under EYU688
  measure: Time from fever onset to clinical recovery
  time frame: From fever onset to Day 15
  description: Assessment of the dengue fever clinical evolution under EYU688
  measure: PK parameter (Cmax)
  time frame: From Day 1 to Day 6
  description: Pharmacokinetic assessment of EYU688 in dengue fever patients
  measure: PK parameter (Tmax)
  time frame: From Day 1 to Day 6
  description: Pharmacokinetic assessment of EYU688 in dengue fever patients
  measure: PK parameter (partial AUCs)
  time frame: From Day 1 to Day 6
  description: Pharmacokinetic assessment of EYU688 in dengue fever patients
  measure: PK concentrations following multiple doses
  time frame: From Day 1 to Day 6
  description: Pharmacokinetic assessment of EYU688 in dengue fever patients
  arm group label: EYU688
  arm group type: Experimental
  description: EYU688 administered by oral route
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Matching placebo
  intervention type: Drug
  intervention name: EYU688
  description: EYU688 administered by oral route
  arm group label: EYU688
  intervention type: Drug
  intervention name: Placebo
  description: Matching placebo administered orally as capsules
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: No
  last name: Novartis Pharmaceuticals
  phone: +41613241111
  email: novartis.email@novartis.com
  last name: Novartis Pharmaceuticals
  responsible party type: Sponsor
  mesh term: Dengue
  sharing ipd: Yes
  ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.