<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/NCT03036046</url>
  </required_header>
  <id_info>
    <org_study_id>F901318C21</org_study_id>
    <nct_id>NCT03036046</nct_id>
  </id_info>
  <brief_title>Safety and Pharmacokinetics of Oral F901318 (Fluconazole and Posaconazole) IN Aml Leukaemia</brief_title>
  <acronym>SAFEGUARDFP</acronym>
  <official_title>An Open Label Phase IIa Clinical Study to Evaluate the Safety and Pharmacokinetics of Oral F901318 (Combined With Fluconazole and Posaconazole) in AML</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>F2G Biotech GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Clinical Trials Centre Cologne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Klinik für Hämatologie, Aachen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medizinische Klinik Würzburg</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>F2G Biotech GmbH</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>
      Non-randomized, multi-centre, open label, uncontrolled, multiple dose, phase IIa study.&#xD;
&#xD;
      A total of 18 patients diagnosed with acute myeloid leukaemia (AML) scheduled for&#xD;
      chemotherapy and expected to be neutropenic (&lt;500 Absolute neutrophil count (ANC)/µl) for &gt;10&#xD;
      days will be treated. F901318 will be given in conjunction with fluconazole or posaconzaole&#xD;
      in order to assess safe treatment regimens for both combinations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      'F901318 has potent in vitro efficacy against Aspergillus spp. including azole-resistant&#xD;
      strains and consistent efficacy in in vivo mouse models of infection. F901318 is active by&#xD;
      both oral and intravenous routes of administration in preclinical efficacy studies.&#xD;
&#xD;
      Non-clinical studies and phase I clinical trials show that F901318 has a good overall safety&#xD;
      profile and limited potential for drug-drug interactions. F901318 exhibits a highly promising&#xD;
      profile which can potentially address the critical treatment requirements for invasive&#xD;
      Aspergillus infections in a changing clinical environment in which new classes of antifungals&#xD;
      are needed.&#xD;
&#xD;
      This phase IIa study aims to confirm PK and safety information of F901318 from phase I and&#xD;
      bridge them to a neutropenic AML patient population, which represents the main population for&#xD;
      future efficacy trials. Coadministration of fluconazole or posaconazole will allow&#xD;
      recognizing potential factors of suboptimal F901318 exposure without the risk of fatal&#xD;
      disseminating infection.'&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study no longer required&#xD;
  </why_stopped>
  <start_date type="Anticipated">March 2017</start_date>
  <completion_date type="Anticipated">March 2018</completion_date>
  <primary_completion_date type="Anticipated">September 2017</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Patients in group low dose fluconazole will be enrolled ahead of group high dose fluconazole. Group posaconazole will be enrolled in parallel according to prevaling practice in the institutions involved in the study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety (adverse events)</measure>
    <time_frame>63 days</time_frame>
    <description>Adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (Area under concentration/time curve)</measure>
    <time_frame>14 days</time_frame>
    <description>Area under concentration/time curve</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>F901318 with fluconazole low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>safety assessment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>F901318 with fluconazole high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>safety assessment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>F901318 with posaconazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>safety assessment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>F901318 with fluconazole low dose</intervention_name>
    <description>adverse events</description>
    <arm_group_label>F901318 with fluconazole low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>F901318 with fluconazole high dose</intervention_name>
    <description>adverse events</description>
    <arm_group_label>F901318 with fluconazole high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>F901318 with posaconazole</intervention_name>
    <description>adverse events</description>
    <arm_group_label>F901318 with posaconazole</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participating patients need to fulfil all of the following criteria:&#xD;
&#xD;
               1. Patients diagnosed with AML and entering treatment of chemotherapy.&#xD;
&#xD;
               2. Patients are expected to be neutropenic (ANC &lt;500/µl) for &gt;10 days.&#xD;
&#xD;
               3. Provision of written informed consent prior to any study specific procedures.&#xD;
&#xD;
               4. Ability and willingness to comply with the protocol.&#xD;
&#xD;
               5. Patients aged over 18 years.&#xD;
&#xD;
               6. Patients with body weight ≥60 kg&#xD;
&#xD;
               7. Group F only: patient receives according to local clinical standard either&#xD;
&#xD;
                    -  no fungal prophylaxis or&#xD;
&#xD;
                    -  only topical fungal prophylaxis (e.g. Ampho moronal®) or&#xD;
&#xD;
                    -  fluconazole as routine fungal prophylaxis&#xD;
&#xD;
               8. Group P only: patient receives posaconazole as fungal prophylaxis according to&#xD;
                  local clinical standard&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any of the following will exclude a patient from the study:&#xD;
&#xD;
               1. Documented lung infiltrate at screening.&#xD;
&#xD;
               2. Evidence for active fungal infection, such as documented serum GMI ≥0.5 at&#xD;
                  screening (within 5 days before study start)&#xD;
&#xD;
               3. Current IFD or prior history of IFD or patients who received systemic antifungal&#xD;
                  therapy for proven or probable IFD in the last 12 months.&#xD;
&#xD;
               4. Patients who received any systemic antifungal therapy for more than 72 hours&#xD;
                  immediately prior to first administration of study medication. Echinocandins,&#xD;
                  posaconazole (group P, see also inclusion criterion 8), and topical polyenes or&#xD;
                  nystatin are acceptable.&#xD;
&#xD;
               5. Concomitant exposure to phenobarbital and long acting barbiturates, triazolam,&#xD;
                  carbamazepine, phenytoin, pimozide, cisaprid, efavirenz, ritonavir, rifabutin,&#xD;
                  rifampicin, ergot alkaloids (ergotamine, dihydroergotamin), ibrutinib,&#xD;
                  idelalisib, vinca alkaloids, digoxin, dofetilide, quinidine, St. John´s wort,&#xD;
                  everolimus, sirolimus, astemizole, terfenadine, methadone, alfentanil, fentanyl&#xD;
                  and other structurally related opiates, warfarin (see also section 8.8 for&#xD;
                  details).&#xD;
&#xD;
               6. Documented prolongation of the QTc interval (&gt;450 ms).&#xD;
&#xD;
               7. Concomitant medication that prolongs QT interval (except for cytostatic drugs&#xD;
                  used during chemotherapy, such as mitoxantrone).&#xD;
&#xD;
               8. Any other concomitant medical condition that, in the opinion of the investigator,&#xD;
                  may be an unacceptable additional risk to the patient should he/she participate&#xD;
                  in the study.&#xD;
&#xD;
               9. History of convulsion.&#xD;
&#xD;
              10. Female patients only: Positive result of pregnancy test or breastfeeding.&#xD;
&#xD;
              11. Female patients of childbearing potential who do not practice sexual abstinence&#xD;
                  as their common way of life and confirm to stay sexually abstinent also during&#xD;
                  their participation in the study or who do not use or do not agree to use&#xD;
                  appropriate contraceptive methods (prior to and during the study, including 14&#xD;
                  days after the last dose of study therapy) as defined in ICH guideline M3(R2) on&#xD;
                  non-clinical safety studies for the conduct of human clinical trials and&#xD;
                  marketing authorisation for pharmaceuticals (EMA/CPMP/ICH/286/1995). Hormonal&#xD;
                  contraception alone is not considered appropriate. See section 9.3.2 for&#xD;
                  additional information.&#xD;
&#xD;
              12. Known hypersensitivity to any component of the study medication.&#xD;
&#xD;
              13. A history of additional risk factors for Torsade de pointes (e.g., heart failure,&#xD;
                  hypokalaemia, cardiomyopathy, sinus bradycardia, symptomatic arrhythmias, family&#xD;
                  history of long QT Syndrome).&#xD;
&#xD;
              14. Patient has had acute hepatitis in the prior 6 months, chronic hepatitis,&#xD;
                  cirrhosis (any Child-Pugh class), acute hepatic failure, or acute decompensation&#xD;
                  of chronic hepatic failure&#xD;
&#xD;
              15. Presence of hepatic disease as indicated by aspartate aminotransferase (AST) or&#xD;
                  alanine transaminase (ALT) &gt;3 × upper limit of normal (ULN) at Screening.&#xD;
                  Patients with AST and/or ALT &gt;3 × ULN and &lt;5 × ULN are eligible if these&#xD;
                  elevations are acute, not accompanied by a total bilirubin ≥2xULN and documented&#xD;
                  by the investigator as being directly related to an infectious process being&#xD;
                  treated. During the clinical study, the investigator is responsible for, without&#xD;
                  delay, determining whether the patient meets potential Hy's law criteria&#xD;
                  (according to FDA [16]).&#xD;
&#xD;
              16. Patient has a total bilirubin &gt;3 × ULN, unless isolated hyperbilirubinemia is&#xD;
                  directly related to an acute infection or due to known Gilbert's disease.&#xD;
&#xD;
              17. Calculated creatinine clearance (CrCl) &lt;50 mL/minute.&#xD;
&#xD;
              18. Medical history of oliguria (&lt;20 mL/h) unresponsive to fluid challenge.&#xD;
&#xD;
              19. Suspected other or additional cause for neutropenia or immunosuppression (other&#xD;
                  than AML or myelodysplastic syndrome).&#xD;
&#xD;
              20. Any other medical condition, which may affect the clinical evaluability of the&#xD;
                  patient.&#xD;
&#xD;
              21. Patients previously enrolled in this study.&#xD;
&#xD;
              22. Patient has participated or intends to participate in any other clinical study&#xD;
                  that involves the administration of an investigational medication at the time of&#xD;
                  presentation, during the course of the study, or during the 30 days prior to&#xD;
                  study start. New combinations of labelled substances for chemotherapy are&#xD;
                  allowed.&#xD;
&#xD;
              23. Chronic external ocular disease&#xD;
&#xD;
              24. Contact lens use intended during study treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oliver A Cornely, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Cologne</affiliation>
  </overall_official>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 30, 2017</study_first_posted>
  <last_update_submitted>February 13, 2018</last_update_submitted>
  <last_update_submitted_qc>February 13, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2018</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>Leukemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluconazole</mesh_term>
    <mesh_term>Posaconazole</mesh_term>
    <mesh_term>Olorofim</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03036046
org study id: F901318C21
nct id: NCT03036046
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Non-randomized, multi-centre, open label, uncontrolled, multiple dose, phase IIa study.

      A total of 18 patients diagnosed with acute myeloid leukaemia (AML) scheduled for
      chemotherapy and expected to be neutropenic (<500 Absolute neutrophil count (ANC)/µl) for >10
      days will be treated. F901318 will be given in conjunction with fluconazole or posaconzaole
      in order to assess safe treatment regimens for both combinations.
'F901318 has potent in vitro efficacy against Aspergillus spp. including azole-resistant
      strains and consistent efficacy in in vivo mouse models of infection. F901318 is active by
      both oral and intravenous routes of administration in preclinical efficacy studies.

      Non-clinical studies and phase I clinical trials show that F901318 has a good overall safety
      profile and limited potential for drug-drug interactions. F901318 exhibits a highly promising
      profile which can potentially address the critical treatment requirements for invasive
      Aspergillus infections in a changing clinical environment in which new classes of antifungals
      are needed.

      This phase IIa study aims to confirm PK and safety information of F901318 from phase I and
      bridge them to a neutropenic AML patient population, which represents the main population for
      future efficacy trials. Coadministration of fluconazole or posaconazole will allow
      recognizing potential factors of suboptimal F901318 exposure without the risk of fatal
      disseminating infection.'
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Patients in group low dose fluconazole will be enrolled ahead of group high dose fluconazole. Group posaconazole will be enrolled in parallel according to prevaling practice in the institutions involved in the study
primary purpose: Treatment
masking: None (Open Label)
measure: Safety (adverse events)
time frame: 63 days
description: Adverse events
measure: Pharmacokinetics (Area under concentration/time curve)
time frame: 14 days
description: Area under concentration/time curve
arm group label: F901318 with fluconazole low dose
arm group type: Experimental
description: safety assessment
arm group label: F901318 with fluconazole high dose
arm group type: Experimental
description: safety assessment
arm group label: F901318 with posaconazole
arm group type: Experimental
description: safety assessment
intervention type: Drug
intervention name: F901318 with fluconazole low dose
description: adverse events
arm group label: F901318 with fluconazole low dose
intervention type: Drug
intervention name: F901318 with fluconazole high dose
description: adverse events
arm group label: F901318 with fluconazole high dose
intervention type: Drug
intervention name: F901318 with posaconazole
description: adverse events
arm group label: F901318 with posaconazole
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Oliver A Cornely, MD
role: Principal Investigator
affiliation: University Hospital Cologne
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Fluconazole
mesh term: Posaconazole
mesh term: Olorofim
sharing ipd: No