<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/NCT02210182</url>
  </required_header>
  <id_info>
    <org_study_id>OCZ103-300-1401</org_study_id>
    <nct_id>NCT02210182</nct_id>
  </id_info>
  <brief_title>A Phase I Clinical Study on a New Oral Pentamidine Formulation in Hepatocellular Carcinoma</brief_title>
  <official_title>A Phase I Clinical Study on the Hepatic Uptake, Pharmacokinetics, Safety and Tolerance of a New Oral Pentamidine Formulation in Hepatocellular Carcinoma Subjects Undergoing Thermal Ablation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oncozyme Pharma Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Oncozyme Pharma Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate on the Hepatic Uptake, Pharmacokinetics, Safety&#xD;
      and Tolerance of a New Oral Pentamidine Formulation in Hepatocellular Carcinoma Subjects&#xD;
      Undergoing Thermal Ablation&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1, randomized, double-blind, placebo-controlled, sequential-group&#xD;
      administration of a new oral pentamidine formulation to investigate its hepatic uptake,&#xD;
      pharmacokinetics, safety and tolerance in subjects with hepatocellular carcinoma who&#xD;
      undergoes thermal ablation procedure&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</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>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>pharmacokinetics</measure>
    <time_frame>3 days</time_frame>
    <description>Liver concentration of pentamidine in hepatocellular carcinoma tumor and surrounding tissue after oral administration for 3 days at different doses, measured in liver biopsies obtained during thermal ablation procedure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>plasma Pharmacokinetics</measure>
    <time_frame>3 days</time_frame>
    <description>Plasma concentration of pentamidine after oral administration for 3 days at different doses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>3 days</time_frame>
    <description>Safety as assessed by adverse events (AE), vital signs and laboratory parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>markers of efficacy</measure>
    <time_frame>3 days</time_frame>
    <description>The levels of Plasma pharmacodynamic markers of efficacy: ALT and AST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarker</measure>
    <time_frame>3 days</time_frame>
    <description>Tissue biomarker of mechanism of action: Endo-exonuclease</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Oral pentamidine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral pentamidine given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral Pentamidine</intervention_name>
    <description>Oral pentamidine given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days</description>
    <arm_group_label>Oral pentamidine</arm_group_label>
    <other_name>VLX103</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female subjects&#xD;
&#xD;
          2. 18 years of age or older&#xD;
&#xD;
          3. Radiologically established diagnosis of hepatocellular carcinoma (HCC) with tumor&#xD;
             diameter ≤ 5 cm&#xD;
&#xD;
          4. Suitable for and scheduled to undergo thermal ablation as treatment&#xD;
&#xD;
          5. Have a Barcelona score of 0 or A&#xD;
&#xD;
          6. Have a Child Pugh score of A or B&#xD;
&#xD;
          7. Legally and mentally able to give informed consent to participate in the study&#xD;
&#xD;
          8. Signature of a dated Informed Consent Form (ICF) indicating that the subject has been&#xD;
             informed of all the relevant aspects of the trial prior to enrolment&#xD;
&#xD;
          9. Willingness and ability to comply with scheduled visits and trial procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of uncontrolled diabetes, defined as glycated hemoglobin (Hb1Ac) ≥ 8.0&#xD;
&#xD;
          2. History of clinically significant hypoglycaemia, with fasting blood glucose &lt; 3 mmol/L&#xD;
             within 3 months prior to signature of ICF&#xD;
&#xD;
          3. Presence of clinically significant renal impairment, defined as a creatinine clearance&#xD;
             &lt; 60 mL/min&#xD;
&#xD;
          4. Systolic Blood Pressure &lt; 100 mm Hg (if deemed clinically significant by the treating&#xD;
             physician)&#xD;
&#xD;
          5. Current or recent (&lt; 2 years) history of pancreatitis&#xD;
&#xD;
          6. International Normalised Ratio (INR) &gt; 1.5 or presence of severe coagulation disorders&#xD;
             (vg but limited to prothrombin activity &lt; 40% or a platelet count of &lt; 40,000 / mm3)&#xD;
&#xD;
          7. Presence of known vascular invasion, bile duct invasion or extrahepatic metastasis&#xD;
&#xD;
          8. Presence of portal venous thrombosis&#xD;
&#xD;
          9. Concomitant therapy with other investigational agents or participation in another&#xD;
             clinical trial within 3 months of signature of ICF&#xD;
&#xD;
         10. Previous use of pentamidine with treatment discontinuation of less than 6 months prior&#xD;
             to signature of ICF&#xD;
&#xD;
         11. Any of the following conditions: Ongoing clinically significant cardiac dysrhythmias&#xD;
             such as atrial fibrillation ; QTc interval &gt; 450 msec for males or &gt; 470 msec for&#xD;
             females or uncontrolled intercurrent cardiac illness, e.g. unstable angina; severe&#xD;
             coronary disease, ventricular arrhythmias, bradycardia &lt; 50 bpm (unless caused by&#xD;
             beta-blocker); a history of additional risk factors for torsades de pointes (e.g.,&#xD;
             heart failure or family history of Long QTC Syndrome)&#xD;
&#xD;
         12. Presence of clinically significant hypokalemia or hypomagnesemia&#xD;
&#xD;
         13. Concurrent use of nephrotoxic drugs&#xD;
&#xD;
         14. Concurrent use of cardiotoxic drugs&#xD;
&#xD;
         15. Concurrent use of drugs that may be associated with pancreatitis&#xD;
&#xD;
         16. History of allergy or hypersensitivity to pentamidine&#xD;
&#xD;
         17. Pregnancy or breastfeeding. All female subjects of childbearing potential must have a&#xD;
             negative urine pregnancy test prior to first dose of study medication.&#xD;
&#xD;
         18. Acute or chronic severe medical or psychiatric condition, or laboratory abnormality&#xD;
             that would impart, in the judgement of the investigator, excess risk associated with&#xD;
             trial participation of study drug administration, or which in the judgement of the&#xD;
             investigator, would make the subject inappropriate for entry into this trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Patrick Colin, B.Pharm, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Verlyx Pharma Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dr. Kelly Burak</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N4Z6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dr Morris Sherman</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dr Marc Bilodeau</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X 3J4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 6, 2014</study_first_posted>
  <last_update_submitted>March 11, 2016</last_update_submitted>
  <last_update_submitted_qc>March 11, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 14, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatocellular carcinoma</keyword>
  <keyword>Oral Pentamidine</keyword>
  <keyword>Endo-exonuclease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pentamidine</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/NCT02210182
org study id: OCZ103-300-1401
nct id: NCT02210182
lead sponsor: 
has dmc: Yes
The purpose of this study is to investigate on the Hepatic Uptake, Pharmacokinetics, Safety
      and Tolerance of a New Oral Pentamidine Formulation in Hepatocellular Carcinoma Subjects
      Undergoing Thermal Ablation
This is a Phase 1, randomized, double-blind, placebo-controlled, sequential-group
      administration of a new oral pentamidine formulation to investigate its hepatic uptake,
      pharmacokinetics, safety and tolerance in subjects with hepatocellular carcinoma who
      undergoes thermal ablation procedure
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: pharmacokinetics
time frame: 3 days
description: Liver concentration of pentamidine in hepatocellular carcinoma tumor and surrounding tissue after oral administration for 3 days at different doses, measured in liver biopsies obtained during thermal ablation procedure
measure: plasma Pharmacokinetics
time frame: 3 days
description: Plasma concentration of pentamidine after oral administration for 3 days at different doses
measure: Adverse events
time frame: 3 days
description: Safety as assessed by adverse events (AE), vital signs and laboratory parameters
measure: markers of efficacy
time frame: 3 days
description: The levels of Plasma pharmacodynamic markers of efficacy: ALT and AST
measure: Biomarker
time frame: 3 days
description: Tissue biomarker of mechanism of action: Endo-exonuclease
arm group label: Oral pentamidine
arm group type: Experimental
description: Oral pentamidine given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days
intervention type: Drug
intervention name: Oral Pentamidine
description: Oral pentamidine given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days
arm group label: Oral pentamidine
other name: VLX103
intervention type: Other
intervention name: Placebo
description: Placebo given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Patrick Colin, B.Pharm, PhD
role: Study Director
affiliation: Verlyx Pharma Inc
facility: 
facility: 
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Pentamidine