<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/NCT04406415</url>
  </required_header>
  <id_info>
    <org_study_id>NAF-101</org_study_id>
    <secondary_id>UG3DA047682-02</secondary_id>
    <nct_id>NCT04406415</nct_id>
  </id_info>
  <brief_title>Oral Nafamostat in Healthy Volunteers</brief_title>
  <official_title>A Single-Center, Double-Blind, Placebo-Controlled, Phase 1b Multiple Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Sequential Dose Regimens of Oral Nafamostat Mesylate in Healthy Volunteers Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ensysce Biosciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Ensysce Biosciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, double-blind, placebo-controlled Multiple Ascending Dose (MAD) study to&#xD;
      evaluate the safety, tolerability and pharmacokinetics of oral nafamostat solution&#xD;
      administered t.i.d.. for up to 5 days in healthy volunteer adult subjects&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects will undergo a medical screening (Days -1 to -10) and, if eligible, informed consent&#xD;
      will be obtained prior to 6 days of confinement at the clinic site. Up to 20 subjects will be&#xD;
      randomized. Subjects will be stratified to include an equal number of male and female&#xD;
      subjects who will receive active drug within each dose cohort, and an equal number of male&#xD;
      and female subjects in the combined placebo group. Separate groups of volunteers will be used&#xD;
      for each dose cohort. There will be 4 dose cohorts in this study with active drug doses of&#xD;
      10, 50, 100, and 200 mg nafamostat in succeeding cohorts. Each cohort of 5 subjects will&#xD;
      enroll 2 male and 2 female to receive active drug and 1 subject (male or female) to receive&#xD;
      placebo for a total of 20 subjects. The placebo subject from each cohort will be combined&#xD;
      into a placebo cohort that will have 4 subjects to compare to 4 subjects in each of the&#xD;
      active dose groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 21, 2020</start_date>
  <completion_date type="Actual">May 14, 2021</completion_date>
  <primary_completion_date type="Actual">November 11, 2020</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Double-blind, placebo-controlled, Multiple Ascending Dose (MAD) study with 4 active drug cohorts</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>This is a double-blinded study. Subjects will not be informed of their treatment assignment (active or placebo); however, investigators and clinical site staff will have access to the randomization codes.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and Tolerability</measure>
    <time_frame>14 Days</time_frame>
    <description>Number of participants with adverse events including out-of-range clinical laboratory measures, vital signs, ECG, and spontaneous adverse event reports throughout the 14 day study period</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (Cmax)</measure>
    <time_frame>Pre-dose (0 hr) and at 0.5, 1, 2, 3, 4, 6, and 8 hr after first dose on Day 1 and again after the last dose on Day 5</time_frame>
    <description>Peak plasma concentrations of nafamostat</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (Tmax)</measure>
    <time_frame>Pre-dose (0 hr) and at 0.5, 1, 2, 3, 4, 6, and 8 hr after first dose on Day 1 and again after the last dose on Day 5</time_frame>
    <description>Time to peak plasma concentrations of nafamostat</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (AUC)</measure>
    <time_frame>Pre-dose (0 hr) and at 0.5, 1, 2, 3, 4, 6, and 8 hr after first dose on Day 1 and again after the last dose on Day 5</time_frame>
    <description>Area under the plasma concentration vs. time curve (AUC) for nafamostat</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Selection</measure>
    <time_frame>5 Days</time_frame>
    <description>Identify dose of nafamostat to maintain a concentration of 3.5 ng/mL (10 nM) or higher for 4 hours or longer after each dose</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Pharmacokinetics</condition>
  <arm_group>
    <arm_group_label>10 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 mg nafamostat three times a day (t.i.d., approximately q8h) for up to 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>50 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 mg nafamostat three times a day (t.i.d., approximately q8h) for up to 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>100 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100 mg nafamostat three times a day (t.i.d., approximately q8h) for up to 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>200 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>200 mg nafamostat three times a day (t.i.d., approximately q8h) for up to 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo administered three times a day (t.i.d., approximately q8h) for up to 5 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nafamostat Mesilate</intervention_name>
    <description>Oral nafamostat, 10, 50, 100, or 200 mg administered three times daily for up to 5 days</description>
    <arm_group_label>10 mg</arm_group_label>
    <arm_group_label>100 mg</arm_group_label>
    <arm_group_label>200 mg</arm_group_label>
    <arm_group_label>50 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral placebo administered three times daily for up to 5 days</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females, age 18 to 70 years old, able and willing to provide written informed&#xD;
             consent to participate in the study;&#xD;
&#xD;
          2. Subjects must be in generally good health as determined by pre-study medical history,&#xD;
             physical examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG);&#xD;
&#xD;
          3. Subjects must be willing to remain in confinement at the clinical study unit for 6.5&#xD;
             consecutive days and to return to the unit at Day 14±2 for followup safety&#xD;
             assessments;&#xD;
&#xD;
          4. Body mass index (BMI) 19-32 kg/m2;&#xD;
&#xD;
          5. Normal blood pressure (BP) [systolic BP 90-140 mmHg, diastolic BP 50-90 mmHg] and&#xD;
             heart rate (HR) [resting HR 45-90 beats per minute (bpm)] without medication;&#xD;
&#xD;
          6. Clinical chemistry profile including electrolytes, alkaline phosphatase (ALK), lactate&#xD;
             dehydrogenase (LDH), creatine phosphokinase (CPK), creatinine, and urea must be within&#xD;
             the normal range without medication; screening liver enzymes may be up to 1.5x normal&#xD;
             range; screening CPK must be within 2x normal range;&#xD;
&#xD;
          7. Urinalysis including urinary creatinine must be within normal limits (trace findings&#xD;
             and minor deviations are acceptable per the clinical decision of the Principal&#xD;
             Investigator);&#xD;
&#xD;
          8. Subjects must be non-smokers or willing to abstain from smoking for the duration of&#xD;
             study;&#xD;
&#xD;
          9. Subjects must be able to read, understand and follow the study instructions;&#xD;
&#xD;
         10. Male subjects and their female sexual partners must agree to use double barrier&#xD;
             contraception during the study period and for 2 months afterward, or provide proof of&#xD;
             post-menopausal state (minimum 1 year) or surgical sterility.&#xD;
&#xD;
         11. Female subjects will be non-pregnant, non-lactating, and either postmenopausal for at&#xD;
             least 1 year, or surgically sterile for at least 3 months, or will agree to use&#xD;
             double-barrier contraception from 28 days and/or their last confirmed menstrual period&#xD;
             prior to study enrollment (whichever is longer) until 2 months after Clinic Discharge.&#xD;
             Double barrier contraception may include, but is not limited to, non-hormonal&#xD;
             intrauterine device with spermicide, female condom with spermicide, diaphragm with&#xD;
             spermicide, cervical cap with spermicide; having a male sexual partner who agrees to&#xD;
             use a male condom with spermicide; or having a sterile sexual partner. Females will&#xD;
             refrain from using hormonal contraceptives for at least 28 days prior to study entry&#xD;
             until the end of the study period (Day 14). For all females, the pregnancy test result&#xD;
             must be negative at Screening and Pre-Study Baseline (Days -1 to -10).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of any non-study medication(s) including low dose aspirin for cardiovascular&#xD;
             prophylaxis within one week prior and two weeks after receipt of study drug;&#xD;
&#xD;
          2. Use of chemotherapy agents or history of cancer, other than non-metastatic skin cancer&#xD;
             that has been completely excised, within five years prior to the screening visit;&#xD;
&#xD;
          3. History of bacterial or viral infection requiring treatment with antibiotics or&#xD;
             antivirals within 1 month of study;&#xD;
&#xD;
          4. History of congestive heart failure;&#xD;
&#xD;
          5. Use of drugs which are P450 inducers or inhibitors within the past 30 days (e.g.&#xD;
             cimetidine, paroxetine, fluoxetine, haloperidol, ketoconazole, itraconazole,&#xD;
             fluconazole, erythromycin, clarithromycin);&#xD;
&#xD;
          6. Use of any dietary aids or foods that are known to modulate drug metabolizing enzymes&#xD;
             (e.g. St. John's Wort, grapefruit juice) within 14 days of dose administration;&#xD;
&#xD;
          7. History of seizure disorder;&#xD;
&#xD;
          8. Serious psychosocial co-morbidities;&#xD;
&#xD;
          9. Cognitive or psychiatric disorders, or any other condition that could interfere with&#xD;
             compliance with study procedures and/or confinement in a clinical study unit for 6.5&#xD;
             days;&#xD;
&#xD;
         10. History of drug or alcohol abuse within one year prior to screening;&#xD;
&#xD;
         11. Use of any other investigational drug within 1 month prior to enrollment;&#xD;
&#xD;
         12. Use of prescription drugs within 1 month prior to enrollment;&#xD;
&#xD;
         13. Use of over the counter medication excluding routine vitamins, but including mega-dose&#xD;
             vitamin therapy, within one week of enrollment;&#xD;
&#xD;
         14. Donation and/or receipt of any blood or blood products within 3 months prior to&#xD;
             enrollment;&#xD;
&#xD;
         15. Family history of significant cardiac disease (i.e. sudden death in first degree&#xD;
             relative; myocardial infarction prior to 50 years old).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>William K Schmidt, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Ensysce Biosciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Arizona Research Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85023</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>May 24, 2020</study_first_submitted>
  <study_first_submitted_qc>May 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>October 11, 2021</last_update_submitted>
  <last_update_submitted_qc>October 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nafamostat</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/NCT04406415
org study id: NAF-101
secondary id: UG3DA047682-02
nct id: NCT04406415
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized, double-blind, placebo-controlled Multiple Ascending Dose (MAD) study to
      evaluate the safety, tolerability and pharmacokinetics of oral nafamostat solution
      administered t.i.d.. for up to 5 days in healthy volunteer adult subjects
Subjects will undergo a medical screening (Days -1 to -10) and, if eligible, informed consent
      will be obtained prior to 6 days of confinement at the clinic site. Up to 20 subjects will be
      randomized. Subjects will be stratified to include an equal number of male and female
      subjects who will receive active drug within each dose cohort, and an equal number of male
      and female subjects in the combined placebo group. Separate groups of volunteers will be used
      for each dose cohort. There will be 4 dose cohorts in this study with active drug doses of
      10, 50, 100, and 200 mg nafamostat in succeeding cohorts. Each cohort of 5 subjects will
      enroll 2 male and 2 female to receive active drug and 1 subject (male or female) to receive
      placebo for a total of 20 subjects. The placebo subject from each cohort will be combined
      into a placebo cohort that will have 4 subjects to compare to 4 subjects in each of the
      active dose groups.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Double-blind, placebo-controlled, Multiple Ascending Dose (MAD) study with 4 active drug cohorts
primary purpose: Treatment
masking: Single (Participant)
masking description: This is a double-blinded study. Subjects will not be informed of their treatment assignment (active or placebo); however, investigators and clinical site staff will have access to the randomization codes.
measure: Safety and Tolerability
time frame: 14 Days
description: Number of participants with adverse events including out-of-range clinical laboratory measures, vital signs, ECG, and spontaneous adverse event reports throughout the 14 day study period
measure: Pharmacokinetics (Cmax)
time frame: Pre-dose (0 hr) and at 0.5, 1, 2, 3, 4, 6, and 8 hr after first dose on Day 1 and again after the last dose on Day 5
description: Peak plasma concentrations of nafamostat
measure: Pharmacokinetics (Tmax)
time frame: Pre-dose (0 hr) and at 0.5, 1, 2, 3, 4, 6, and 8 hr after first dose on Day 1 and again after the last dose on Day 5
description: Time to peak plasma concentrations of nafamostat
measure: Pharmacokinetics (AUC)
time frame: Pre-dose (0 hr) and at 0.5, 1, 2, 3, 4, 6, and 8 hr after first dose on Day 1 and again after the last dose on Day 5
description: Area under the plasma concentration vs. time curve (AUC) for nafamostat
measure: Dose Selection
time frame: 5 Days
description: Identify dose of nafamostat to maintain a concentration of 3.5 ng/mL (10 nM) or higher for 4 hours or longer after each dose
arm group label: 10 mg
arm group type: Experimental
description: 10 mg nafamostat three times a day (t.i.d., approximately q8h) for up to 5 days
arm group label: 50 mg
arm group type: Experimental
description: 50 mg nafamostat three times a day (t.i.d., approximately q8h) for up to 5 days
arm group label: 100 mg
arm group type: Experimental
description: 100 mg nafamostat three times a day (t.i.d., approximately q8h) for up to 5 days
arm group label: 200 mg
arm group type: Experimental
description: 200 mg nafamostat three times a day (t.i.d., approximately q8h) for up to 5 days
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo administered three times a day (t.i.d., approximately q8h) for up to 5 days
intervention type: Drug
intervention name: Nafamostat Mesilate
description: Oral nafamostat, 10, 50, 100, or 200 mg administered three times daily for up to 5 days
arm group label: 10 mg
arm group label: 100 mg
arm group label: 200 mg
arm group label: 50 mg
intervention type: Drug
intervention name: Placebo
description: Oral placebo administered three times daily for up to 5 days
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: William K Schmidt, PhD
role: Study Director
affiliation: Ensysce Biosciences
facility: 
country: United States
responsible party type: Sponsor
mesh term: Nafamostat
sharing ipd: No