<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/NCT03291418</url>
  </required_header>
  <id_info>
    <org_study_id>ATB-346-P2GIS</org_study_id>
    <nct_id>NCT03291418</nct_id>
  </id_info>
  <brief_title>To Compare the Gastrointestinal Safety of a 14-Day Oral Dosing Regimen of ATB-346 to Sodium Naproxen in Healthy Subjects</brief_title>
  <official_title>A Double-Blind, Controlled Study to Compare the Gastrointestinal Safety of a 14-Day Oral Dosing Regimen of ATB-346 to Sodium Naproxen in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Antibe Therapeutics Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Antibe Therapeutics Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Double-Blind, Controlled Study to Compare the Gastrointestinal Safety of a 14-Day Oral&#xD;
      Dosing Regimen of ATB-346 to Sodium Naproxen in Healthy Subjects&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Healthy male and female subjects (n=240) are randomized into two dose groups of 120 subjects&#xD;
      each. Gastroduodenal endoscopies are performed pre-dose and post-dose, i.e., after 14 days of&#xD;
      either ATB-346 (250 mg once daily) or naproxen sodium (550 mg twice daily) and the incidence&#xD;
      of gastric mucosal damage is recorded for comparison between the two treatment arms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 8, 2017</start_date>
  <completion_date type="Actual">April 30, 2018</completion_date>
  <primary_completion_date type="Actual">March 31, 2018</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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Encapsulated tablets</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Gastroduodenal ulcers &gt;=3mm diameter</measure>
    <time_frame>At completion of 14 days of oral dosing</time_frame>
    <description>Incidence of gastric or duodenal ulcers of at least 3 mm diameter with unequivocal depth</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gastroduodenal ulcers &gt;=5mm diameter</measure>
    <time_frame>At completion of 14 days of oral dosing</time_frame>
    <description>Incidence of gastric or duodenal ulcers of at least 5 mm diameter with unequivocal depth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>gastroduodenal erosions</measure>
    <time_frame>At completion of 14 days of oral dosing</time_frame>
    <description>Number of gastric and/or duodenal erosions and/or ulcers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dyspepsia</measure>
    <time_frame>At completion of 14 days of oral dosing</time_frame>
    <description>Incidence of dyspepsia leading to study withdrawal</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematocrit</measure>
    <time_frame>At completion of 14 days of oral dosing</time_frame>
    <description>Change from baseline in hematocrit levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Thromboxane B2 levels</measure>
    <time_frame>At completion of 14 days of oral dosing</time_frame>
    <description>Changes from baseline in ex vivo whole blood thromboxane B2 (TXB2) synthesis</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">258</enrollment>
  <condition>Gastric Ulcer</condition>
  <arm_group>
    <arm_group_label>ATB-346 OR Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention: Drug: ATB-346 dosed orally at 250 mg once daily for 14 days Intervention: Drug: Placebo (for ATB-346) dosed once daily for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Naproxen sodium</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intervention: Drug: naproxen sodium dosed orally at 550 mg twice daily for 14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ATB-346 OR Placebo</intervention_name>
    <description>Comparison of gastrointestinal effects</description>
    <arm_group_label>ATB-346 OR Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Naproxen sodium</intervention_name>
    <description>Comparison of gastrointestinal effects</description>
    <arm_group_label>Naproxen sodium</arm_group_label>
    <other_name>Naprosyn</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Adult subjects ≥18 to ≤65 years of age 2. Healthy subject with no history of&#xD;
             significant gastrointestinal (GI) disease, arthritis or bleeding disorders 3. Subject&#xD;
             with laboratory values within normal and acceptable ranges or out of range laboratory&#xD;
             values deemed non-clinically significant, as per investigator discretion 4. BMI ≤35&#xD;
             kg/m2 5. Non-smoker for &gt;1 month prior to screening 6. Subject able and willing to&#xD;
             give written informed consent, and understand and adhere to protocol requirements 7.&#xD;
             Female of childbearing potential using adequate birth control for at least 28 days&#xD;
             prior to the first dose of the study drug and for 60 days after the last drug&#xD;
             administration, as specified in one of the options below:&#xD;
&#xD;
               -  Abstinence from heterosexual intercourse&#xD;
&#xD;
               -  Contraception to include birth control pills, injectable/implant/transdermal&#xD;
                  patch&#xD;
&#xD;
               -  Intrauterine device&#xD;
&#xD;
               -  Cervical cap or diaphragm with use of spermicide&#xD;
&#xD;
               -  Condom with spermicide Male subjects with female partners of childbearing&#xD;
                  potential must agree to abstain from sexual intercourse or use on the above forms&#xD;
                  of contraception for a period of 3 months following the last drug administration.&#xD;
&#xD;
                  8. Female of non-childbearing potential who is either sterile (via complete&#xD;
                  hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state&#xD;
                  for at least one year 9. Subject who consumes no more than 1 alcoholic&#xD;
                  serving/drink per day (e.g. 355 mL (12 fluid (fl) ounces (oz)) of regular beer;&#xD;
                  148 mL (5 fl oz) of wine; 45 mL (1.5 fl oz) of distilled spirits) 10. Subject&#xD;
                  willing to refrain from alcohol consumption for 48 hours prior to the screening&#xD;
                  endoscopy and randomization, and 48 hours prior to the Day 14 endoscopy.&#xD;
&#xD;
                  11. Screening endoscopy is free from any observable gastroduodenal erosions or&#xD;
                  ulcers, and no greater than 10 mucosal petechiae.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Subject with abnormal baseline laboratory values deemed to be clinically&#xD;
             significant by the Investigator 2. Ongoing use of any prescription or over-the-counter&#xD;
             medications, or natural/herbal or vitamin preparations, that in the opinion of the&#xD;
             Investigator would interfere with the study objectives, or impact subject safety (with&#xD;
             the exception of systemic contraceptives and hormone replacement therapy) 3. Use of&#xD;
             investigational drugs up to thirty (30) days before screening 4. Use of the following&#xD;
             medications within two weeks prior to randomization:&#xD;
&#xD;
               1. NSAIDs, Aspirin, aspirin-containing products or naproxen-containing medications,&#xD;
                  NSAID-containing products&#xD;
&#xD;
               2. Proton pump inhibitors&#xD;
&#xD;
               3. H-2 blockers&#xD;
&#xD;
               4. Anti-platelet agents&#xD;
&#xD;
               5. Anti-coagulants&#xD;
&#xD;
               6. Antimicrobials&#xD;
&#xD;
               7. Other gastroprotective agents such as antacids, misoprostol, or&#xD;
                  bismuth-containing products 5. Subject-reported past history of gastrointestinal&#xD;
                  ulcer or gastrointestinal bleeding, or any clinically significant&#xD;
                  gastrointestinal disease.&#xD;
&#xD;
                  6. Positive for Helicobacter pylori urea breath test at the screening visit 7.&#xD;
                  Clinically significant gastrointestinal, hepatic or renal disease, or any other&#xD;
                  conditions known to significantly impact or interfere with absorption,&#xD;
                  distribution, metabolism or elimination of the investigational drug(s) 8.&#xD;
                  Clinically significant past or present diseases or illnesses that, in the opinion&#xD;
                  of the investigator, would interfere with the study objectives or integrity or&#xD;
                  with the subject's safety.&#xD;
&#xD;
                  9. Subject with seated pulse rates &lt;50 beats per minute (bpm) or &gt;100 bpm at&#xD;
                  screening 10. Seated blood pressure &lt;100/60 mm Hg or &gt;140/90 mm Hg at screening&#xD;
                  11. Known hypersensitivities to naproxen, other non-steroidal anti-inflammatory&#xD;
                  (NSAID) agents, related products (including excipients and formulations) 12.&#xD;
                  Known hypersensitivities to drugs used for sedation during endoscopy 13. Severe&#xD;
                  hypersensitivity (including angioedema) to any drugs 14. Use of medications with&#xD;
                  known drug-drug interactions including potent enzyme-modifying drugs, potent&#xD;
                  inhibitors and/or inducers of CYP enzymes (such as fluoxetine, barbiturates or&#xD;
                  St. John's Wort) in the previous thirty (30) days before randomization 15. Female&#xD;
                  who is pregnant or breastfeeding 16. Positive test for HIV antigen/antibody&#xD;
                  combination, hepatitis B surface antigen (HBsAg), or anti-Hepatitis C virus tests&#xD;
                  17. Positive urine drug test at screening 18. Positive urine alcohol test prior&#xD;
                  to the screening endoscopy 19. Any clinically significant illness up to thirty&#xD;
                  (30) days before screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Deepen Patel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Topstone Clinical Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Topstone Clinical Research</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M9C 4Z5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>June 4, 2018</last_update_submitted>
  <last_update_submitted_qc>June 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy Volunteers, ATB-346, Naproxen sodium, GI safety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach Ulcer</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Naproxen</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/NCT03291418
org study id: ATB-346-P2GIS
nct id: NCT03291418
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
A Double-Blind, Controlled Study to Compare the Gastrointestinal Safety of a 14-Day Oral
      Dosing Regimen of ATB-346 to Sodium Naproxen in Healthy Subjects
Healthy male and female subjects (n=240) are randomized into two dose groups of 120 subjects
      each. Gastroduodenal endoscopies are performed pre-dose and post-dose, i.e., after 14 days of
      either ATB-346 (250 mg once daily) or naproxen sodium (550 mg twice daily) and the incidence
      of gastric mucosal damage is recorded for comparison between the two treatment arms.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Encapsulated tablets
measure: Gastroduodenal ulcers >=3mm diameter
time frame: At completion of 14 days of oral dosing
description: Incidence of gastric or duodenal ulcers of at least 3 mm diameter with unequivocal depth
measure: Gastroduodenal ulcers >=5mm diameter
time frame: At completion of 14 days of oral dosing
description: Incidence of gastric or duodenal ulcers of at least 5 mm diameter with unequivocal depth
measure: gastroduodenal erosions
time frame: At completion of 14 days of oral dosing
description: Number of gastric and/or duodenal erosions and/or ulcers
measure: Dyspepsia
time frame: At completion of 14 days of oral dosing
description: Incidence of dyspepsia leading to study withdrawal
measure: Hematocrit
time frame: At completion of 14 days of oral dosing
description: Change from baseline in hematocrit levels
measure: Thromboxane B2 levels
time frame: At completion of 14 days of oral dosing
description: Changes from baseline in ex vivo whole blood thromboxane B2 (TXB2) synthesis
arm group label: ATB-346 OR Placebo
arm group type: Experimental
description: Intervention: Drug: ATB-346 dosed orally at 250 mg once daily for 14 days Intervention: Drug: Placebo (for ATB-346) dosed once daily for 14 days
arm group label: Naproxen sodium
arm group type: Active Comparator
description: Intervention: Drug: naproxen sodium dosed orally at 550 mg twice daily for 14 days
intervention type: Drug
intervention name: ATB-346 OR Placebo
description: Comparison of gastrointestinal effects
arm group label: ATB-346 OR Placebo
intervention type: Drug
intervention name: Naproxen sodium
description: Comparison of gastrointestinal effects
arm group label: Naproxen sodium
other name: Naprosyn
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Deepen Patel, MD
role: Principal Investigator
affiliation: Topstone Clinical Research
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Stomach Ulcer
mesh term: Naproxen