<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/NCT02198807</url>
  </required_header>
  <id_info>
    <org_study_id>JP017</org_study_id>
    <nct_id>NCT02198807</nct_id>
  </id_info>
  <brief_title>Evaluation of Fosmidomycin and Piperaquine in the Treatment of Acute Falciparum Malaria</brief_title>
  <acronym>FOSPIP</acronym>
  <official_title>A Phase IIa Proof of Concept Study to Explore the Efficacy, Tolerability and Safety of Fosmidomycin Sodium When Administered With Piperaquine Tetraphosphate to Adults and Older Children With Acute Uncomplicated Plasmodium Falciparum Malaria</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jomaa Pharma GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Centre de Recherche Médicale de Lambaréné</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Jomaa Pharma GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to explore the role of fosmidomycin and piperaquine as&#xD;
      non-artemisinin-based combination therapy for acute uncomplicated Plasmodium falciparum when&#xD;
      administered over three days.&#xD;
&#xD;
      Together, fosmidomycin and piperaquine fulfil the WHO criteria for combination therapy by&#xD;
      meeting the three key parameters of having different modes of action and different&#xD;
      biochemical targets while exhibiting independent blood schizonticidal activity. Like the&#xD;
      artemisinins, fosmidomycin is fast-acting, has an excellent safety record and is active&#xD;
      against existing drug-resistant parasites. Piperaquine has a long half life protecting&#xD;
      fosmidomycin as a much shorter lived molecule against selection of resistant parasites and&#xD;
      will provide post-treatment prophylaxis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>March 2014</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Actual">July 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Per protocol, PCR-corrected cure rate on Day 28</measure>
    <time_frame>28 days</time_frame>
    <description>Six-hourly asexual counts until negative on three successive occasions.&#xD;
Weekly smears on days 7, 14, 21 and 28</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Per protocol, PCR-corrected cure rates on Day 7 and Day 63</measure>
    <time_frame>63 days</time_frame>
    <description>Weekly smears on days 35 +/- 3 days, 42 +/- 3 days and 63 +/- 3 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Derived parasite reduction ratio at 48 hours</measure>
    <time_frame>2 days</time_frame>
    <description>Six-hourly asexual counts until negative on three successive occasions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parasite clearance time</measure>
    <time_frame>96 hours</time_frame>
    <description>Six-hourly asexual counts until negative on three successive occasions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fever clearance time</measure>
    <time_frame>96 hours</time_frame>
    <description>Six hourly temperature recordings until normal on three successisve occasions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with gametocytes on Day 7</measure>
    <time_frame>7 days</time_frame>
    <description>Smear on Day 7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse event recording</measure>
    <time_frame>28 days</time_frame>
    <description>Recording of vital signs and ECG monitoring&#xD;
Recording of incidence, severity, drug-relatedness and seriousness of AEs and laboratory abnormalites</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Oral Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria</condition>
  <arm_group>
    <arm_group_label>Fosmidomycin-Piperaquine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fosmidomycin sodium capsules 450 mg, dosage: 30mg/kg twice daily for 3 days Piperaquine phosphate tablets 320 mg, dosage: 16 mg/kg once a day for 3 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fosmidomycin-Piperaquine</intervention_name>
    <arm_group_label>Fosmidomycin-Piperaquine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female subjects aged 1 to 60 years inclusive&#xD;
&#xD;
          -  Body weight between 5kg and 90kg inclusive&#xD;
&#xD;
          -  Acute manifestations of a mono-infection with Plasmodium falciparum as determined by&#xD;
             either a rapid diagnostic test for adults or microscopically confirmed by an asexual&#xD;
             parasitaemia of 1,000 to 150,000/uL and fever with an axillary temperature of &gt; 37.5&#xD;
             degress C or oral/rectal/tympanic temperature of &gt; 38.0 degrees C or history of fever&#xD;
             during the previous 72 hours&#xD;
&#xD;
          -  Compliance with contraceptive measures throughout the study period of 63 days in&#xD;
             females of child bearing potential&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        To be eligible for inclusion in the study, subjects must NOT meet any of the following&#xD;
        criteria:&#xD;
&#xD;
          -  Signs of severe/complicated malaria according to WHO criteria&#xD;
&#xD;
          -  Pregnancy as excluded by negative serum human chorionic gonadotrophin (hCG) test&#xD;
&#xD;
          -  Lactation&#xD;
&#xD;
          -  Mixed Plasmodium infection&#xD;
&#xD;
          -  Severe vomiting on three or more occasions in the previous 24 hours&#xD;
&#xD;
          -  Severe diarrhoea on four or more occasions in the previous 24 hours&#xD;
&#xD;
          -  Concomitant disease masking assessment of response including&#xD;
&#xD;
               -  abnormal liver function tests with bilirubin &gt; 40 µmol/L, aspartate&#xD;
                  aminotransferase (ASAT) and alanine aminotransferase (ALAT) levels &gt; x 2 upper&#xD;
                  limit of normal&#xD;
&#xD;
               -  impaired renal function with creatinine level &gt; x 2 upper limit of normal&#xD;
&#xD;
               -  haemoglobin level &lt; 7.5g/dl&#xD;
&#xD;
               -  white cell count &gt; 12000/µL&#xD;
&#xD;
          -  History of cardiovascular disease including arrhythmia with QTc interval ≥ 450msec,&#xD;
             respiratory disease including active tuberculosis, hepatic disease including jaundice,&#xD;
             renal failure, malignancy, neurological disorders including convulsions and&#xD;
             psychiatric disturbances&#xD;
&#xD;
          -  History of immunological disease including Hepatitis A, B and C and HIV-AIDS&#xD;
&#xD;
          -  Severe malnutrition&#xD;
&#xD;
          -  History of hypersensitivity or adverse reactions to fosmidomycin, piperaquine,&#xD;
             artesunate and mefloquine&#xD;
&#xD;
          -  Treatment with antimalarial and antibacterial agents within the previous 28 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>June 2015</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 24, 2014</study_first_posted>
  <last_update_submitted>June 12, 2015</last_update_submitted>
  <last_update_submitted_qc>June 12, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 15, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
    <mesh_term>Malaria, Falciparum</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Piperaquine</mesh_term>
    <mesh_term>Fosmidomycin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02198807
org study id: JP017
nct id: NCT02198807
lead sponsor: 
collaborator: 
has dmc: No
The objective of this study is to explore the role of fosmidomycin and piperaquine as
      non-artemisinin-based combination therapy for acute uncomplicated Plasmodium falciparum when
      administered over three days.

      Together, fosmidomycin and piperaquine fulfil the WHO criteria for combination therapy by
      meeting the three key parameters of having different modes of action and different
      biochemical targets while exhibiting independent blood schizonticidal activity. Like the
      artemisinins, fosmidomycin is fast-acting, has an excellent safety record and is active
      against existing drug-resistant parasites. Piperaquine has a long half life protecting
      fosmidomycin as a much shorter lived molecule against selection of resistant parasites and
      will provide post-treatment prophylaxis.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Per protocol, PCR-corrected cure rate on Day 28
time frame: 28 days
description: Six-hourly asexual counts until negative on three successive occasions.
Weekly smears on days 7, 14, 21 and 28
measure: Per protocol, PCR-corrected cure rates on Day 7 and Day 63
time frame: 63 days
description: Weekly smears on days 35 +/- 3 days, 42 +/- 3 days and 63 +/- 3 days
measure: Derived parasite reduction ratio at 48 hours
time frame: 2 days
description: Six-hourly asexual counts until negative on three successive occasions
measure: Parasite clearance time
time frame: 96 hours
description: Six-hourly asexual counts until negative on three successive occasions
measure: Fever clearance time
time frame: 96 hours
description: Six hourly temperature recordings until normal on three successisve occasions
measure: Proportion of subjects with gametocytes on Day 7
time frame: 7 days
description: Smear on Day 7
measure: Adverse event recording
time frame: 28 days
description: Recording of vital signs and ECG monitoring
Recording of incidence, severity, drug-relatedness and seriousness of AEs and laboratory abnormalites
arm group label: Fosmidomycin-Piperaquine
arm group type: Experimental
description: Fosmidomycin sodium capsules 450 mg, dosage: 30mg/kg twice daily for 3 days Piperaquine phosphate tablets 320 mg, dosage: 16 mg/kg once a day for 3 days
intervention type: Drug
intervention name: Fosmidomycin-Piperaquine
arm group label: Fosmidomycin-Piperaquine
criteria: 
gender: All
minimum age: 1 Year
maximum age: 60 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Malaria
mesh term: Malaria, Falciparum
mesh term: Piperaquine
mesh term: Fosmidomycin