<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/NCT03781791</url>
  </required_header>
  <id_info>
    <org_study_id>ENT-01-030</org_study_id>
    <nct_id>NCT03781791</nct_id>
  </id_info>
  <brief_title>Orally Administered ENT-01 for Parkinson's Disease-Related Constipation (KARMET)</brief_title>
  <acronym>KARMET</acronym>
  <official_title>A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate Safety, Tolerability and Efficacy of Orally Administered ENT-01 for the Treatment of Parkinson's Disease-Related Constipation (KARMET)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Enterin Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Enterin Inc.</source>
  <oversight_info>
    <has_dmc>Yes</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 study will be conducted as a multi-center, randomized, double-blind, placebo-controlled&#xD;
      study. Approximately 72 patients will be randomized 3:1 to treatment or placebo, with&#xD;
      approximately 54 patients allocated to receive the active investigational product and&#xD;
      approximately 18 patients allocated to receive placebo.&#xD;
&#xD;
      - Study Update-&#xD;
&#xD;
      Amendment 3 - In this amendment, an additional 80 patients (approximately) will be randomized&#xD;
      1:1 to treatment or placebo (double-blind) with approximately 40 subjects allocated to each&#xD;
      group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be conducted on an out-patient basis. Each patient will have 6 visits to the&#xD;
      clinic: a screening visit, a randomization visit, 3 follow up visits, and 1 end of study&#xD;
      visit.&#xD;
&#xD;
      Patient randomization will be stratified based upon the baseline weekly complete spontaneous&#xD;
      bowel movement rate (CSBM) established during the screening period. Patients will be allowed&#xD;
      to adjust their dosing, based upon protocol specifications. Rescue medications will be&#xD;
      provided to all patients to ensure they move their bowels on a regular basis.&#xD;
&#xD;
      Patients will also be asked to participate in up to 2 sub-studies: a pk study and/or a stool&#xD;
      microbiome study. The first 20 patients to consent to the pk study will have additional blood&#xD;
      samples taken at randomization and at 2 follow up visits. The first 20 patients to consent to&#xD;
      the stool microbiome study will provide stool samples at randomization and at 2 follow up&#xD;
      visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 10, 2018</start_date>
  <completion_date type="Actual">December 14, 2021</completion_date>
  <primary_completion_date type="Actual">December 14, 2021</primary_completion_date>
  <phase>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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment Related Adverse Events-Safety Endpoint</measure>
    <time_frame>Through Study treatment up to 10 weeks</time_frame>
    <description>The number of treatment related adverse events as reported and assessed by NCI CTCAE v.4.3.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Treatment Related Adverse Event-Tolerability Endpoints</measure>
    <time_frame>Through Study treatment Dosing Period up to 10 weeks</time_frame>
    <description>The number of treatment related adverse events as reported and assessed by NCI CTCAE v.4.3.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in baseline weekly CSBM-Primary Efficacy Endpoint</measure>
    <time_frame>Through Study Treatment Dosing Period up to 10 weeks</time_frame>
    <description>Change from participant's weekly CSBM baseline rate during treatment fixed Dose period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in participant constipation severity from baseline-Secondary Efficacy Endpoints</measure>
    <time_frame>Through Study Treatment Dosing Period up to 10 weeks</time_frame>
    <description>Participant reported change from baseline as assessed according to Bristol Stool rating scale (0-5) of increasing severity of ease of bowel evacuation.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in baseline stool Microbiome - Exploratory Outcome</measure>
    <time_frame>Through Study Treatment Dosing Period and Completion up to 24 weeks</time_frame>
    <description>Collection of participant baseline intestinal microbiome condition as observed in stool to on treatment related effect of ENT-01 on stool microbiome</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">144</enrollment>
  <condition>Constipation</condition>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Active Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ENT-01 tablet will be taken once daily by mouth.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Treatment</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo tablet will be taken once daily by mouth.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Active Investigational Treatment ENT-01</intervention_name>
    <description>ENT-01 will be administered in tablet form, once daily.</description>
    <arm_group_label>Active Treatment</arm_group_label>
    <other_name>ENT-01</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Treatment</intervention_name>
    <description>Placebo will be administered in tablet form, once daily.</description>
    <arm_group_label>Placebo Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects aged 30-90 years, both genders&#xD;
&#xD;
          2. Subjects must provide written informed consent and be willing and able to comply with&#xD;
             study procedures.&#xD;
&#xD;
          3. Subjects must be diagnosed with Parkinson's Disease defined as the presence of at&#xD;
             least three of the following cardinal features, in the absence of alternative&#xD;
             explanations or atypical features: rest tremor, rigidity, bradykinesia and/or&#xD;
             akinesia, postural and gait abnormalities.&#xD;
&#xD;
          4. There are insufficient criteria for Irritable Bowel Syndrome (IBS)&#xD;
&#xD;
          5. Constipation which has been present for over 6 months and is unresponsive to first&#xD;
             line, typically over the counter treatments such as Milk of Magnesia (1g), Miralax&#xD;
             (17g in 8 ounces of water) or the equivalent at least once weekly with an inconsistent&#xD;
             response over a 6-week period or the subject is dissatisfied with first line&#xD;
             treatments.&#xD;
&#xD;
          6. Body mass index (BMI) of 18-40 kg/m2&#xD;
&#xD;
          7. Subjects must fulfill Rome IV criteria for functional constipation which includes 2 or&#xD;
             more of the following:&#xD;
&#xD;
               1. Straining during at least 25% of defecations&#xD;
&#xD;
               2. Lumpy or hard stools in at least 25% of defecations&#xD;
&#xD;
               3. Sensation of incomplete evacuation for at least 25% of defecations&#xD;
&#xD;
               4. Sensation of anorectal obstruction/blockage for at least 25% of defecations&#xD;
&#xD;
               5. Manual maneuvers to facilitate at least 25% of defecations (e.g., digital&#xD;
                  evacuation, support of the pelvic floor)&#xD;
&#xD;
          8. Self-report of fewer than 3 complete spontaneous bowel movements per week&#xD;
&#xD;
          9. Loose stools are rarely present without the use of laxatives&#xD;
&#xD;
         10. Subjects must be able to read, understand, and accurately record data into the diary&#xD;
             to guarantee full participation in the study.&#xD;
&#xD;
         11. Female subjects must have negative serum or urine pregnancy tests and must not be&#xD;
             lactating. For females able to bear children, a hormonal (i.e., oral, implantable, or&#xD;
             injectable) and single-barrier method, or a double-barrier method of birth control&#xD;
             must be used throughout the study. A vasectomized partner will be allowed as one in&#xD;
             conjunction with another single-barrier method.&#xD;
&#xD;
         12. Female subjects unable to bear children must have this documented in the CRF (i.e.,&#xD;
             tubal ligation, hysterectomy, or postmenopausal [defined as a minimum of one year&#xD;
             since the last menstrual period]). Post-menopausal status will be confirmed by&#xD;
             follicle stimulating hormone (FSH) in women less than 60 years of age.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unable or unwilling to provide informed consent or to comply with study procedures.&#xD;
&#xD;
          2. Diagnosis of secondary constipation beyond that of Parkinson's Disease&#xD;
&#xD;
          3. Review of Screening Diaries indicates fewer than 11 days of diary completion and/or 3&#xD;
             or more complete spontaneous bowel movements (CSBM) per week based upon the average&#xD;
             CSBM rate reported during the Screening Period&#xD;
&#xD;
          4. A compromised gastrointestinal system which includes:&#xD;
&#xD;
               1. Structural, metabolic, or functional GI diseases or disorders&#xD;
&#xD;
               2. Acute GI illness within 2 weeks of the screening visit&#xD;
&#xD;
               3. History of major GI surgery within 30 days of the screening visit (a history of&#xD;
                  cholecystectomy, polypectomy, hernia repair or appendicectomy are not&#xD;
                  exclusionary as long as they were performed more than 30 days before the&#xD;
                  screening visit)&#xD;
&#xD;
          5. Unable or unwilling to withdraw from laxatives, opiates, clonazepam, or any&#xD;
             medications which may cause constipation, 2 weeks prior to the dose adjustment period&#xD;
             and throughout the rest of the study.&#xD;
&#xD;
          6. Unable or unwilling to withdraw from proton pump inhibitors and antacids at the end of&#xD;
             the screening period.&#xD;
&#xD;
          7. Unable or unwilling to withdraw from pimavanserin during the study.&#xD;
&#xD;
          8. Any clinically significant abnormalities on screening laboratories or physical&#xD;
             examination requiring further evaluation or treatment.&#xD;
&#xD;
          9. Neurological disorder other than Parkinson's Disease that in the opinion of the&#xD;
             investigator might interfere with the conduct of the study.&#xD;
&#xD;
         10. On treatment with intra-jejunal dopamine or carbidopa/levodopa (i.e. Duopa).&#xD;
&#xD;
         11. Subjects starting a new Parkinson's Disease medication or modifying an existing&#xD;
             medication within 2 weeks prior to enrollment.&#xD;
&#xD;
         12. Unable to maintain a stable diet regimen.&#xD;
&#xD;
         13. Subjects with a cognitive impairment that preclude them from understanding the&#xD;
             informed consent.&#xD;
&#xD;
         14. Subjects placed under legal guardianship.&#xD;
&#xD;
         15. Females who are pregnant or breastfeeding.&#xD;
&#xD;
         16. History of excessive alcohol use or substance abuse.&#xD;
&#xD;
         17. Participation in an investigational drug trial within the month prior to dosing in the&#xD;
             present study.&#xD;
&#xD;
         18. Any other reason, which, in the opinion of the investigator, would confound proper&#xD;
             interpretation of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Zasloff, MD PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Enterin Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Denise Barbut, MD, FRCP</last_name>
    <role>Study Director</role>
    <affiliation>Enterin Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banner Sun Health Research Institute</name>
      <address>
        <city>Sun City</city>
        <state>Arizona</state>
        <zip>85351</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trials, Inc.</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Parkinson's and Movement Disorder Institute</name>
      <address>
        <city>Fountain Valley</city>
        <state>California</state>
        <zip>92708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neuro Pain Medical Center</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <zip>93710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Neuroscience Medical Group</name>
      <address>
        <city>Oxnard</city>
        <state>California</state>
        <zip>93030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SC3 Research - Pasadena</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trial Connections - Care Access Research, Santa Clarita</name>
      <address>
        <city>Santa Clarita</city>
        <state>California</state>
        <zip>91321</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Movement Disorders Center</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Associated Neurologist of Southern CT</name>
      <address>
        <city>Fairfield</city>
        <state>Connecticut</state>
        <zip>06824</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Care Access Research, Norwich</name>
      <address>
        <city>Norwich</city>
        <state>Connecticut</state>
        <zip>06360</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgetown University Hospital</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JEM Research Institute</name>
      <address>
        <city>Atlantis</city>
        <state>Florida</state>
        <zip>33462</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkinson's Disease and Movement Disorders Center of Boca Raton</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elias Research - Floridian Research Institute</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33145</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elias Research - Allied Biomedical Research Institute</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33155</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pharmax Research of South Florida</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33175</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MEDSOL Clinical Research</name>
      <address>
        <city>Port Charlotte</city>
        <state>Florida</state>
        <zip>33952</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkinson's Disease Treatment Center of SWFL</name>
      <address>
        <city>Port Charlotte</city>
        <state>Florida</state>
        <zip>33980</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Intercoastal Medical Group</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Florida</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Palm Beach Neurology and Premier Research Institute</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlanta Center for Medical Research</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BTC Network - Community Clinical Research Center</name>
      <address>
        <city>Anderson</city>
        <state>Indiana</state>
        <zip>46011</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Interspond - The Neuromedical Clinic of Central Louisiana</name>
      <address>
        <city>Alexandria</city>
        <state>Louisiana</state>
        <zip>71301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The NeuroMedical Center, P.C.</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70810</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkinson's and Movement Disorders Center of Maryland</name>
      <address>
        <city>Elkridge</city>
        <state>Maryland</state>
        <zip>21075</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford West Bloomfield Hospital</name>
      <address>
        <city>West Bloomfield</city>
        <state>Michigan</state>
        <zip>48322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurology Associates Clinical Research</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Interspond - Neurology Center of Las Vegas</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>13756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Evolution Research Group - Neuroscience Research Institution</name>
      <address>
        <city>Toms River</city>
        <state>New Jersey</state>
        <zip>08755</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neuroscience Researc Institute of NJ</name>
      <address>
        <city>Toms River</city>
        <state>New Jersey</state>
        <zip>08755</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albany Medical College</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Raleigh Neurology Associates</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest Baptist Medical Center</name>
      <address>
        <city>Wake Forest</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dayton Center for Neurological Disorders</name>
      <address>
        <city>Centerville</city>
        <state>Ohio</state>
        <zip>45459</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elias Research - Neurology Diagnostics Research</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45459</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Toledo Medical Center</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Movement Disorder Clinic of Oklahoma</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn State University</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Interspond - Premier Neurology</name>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <zip>29650</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Interspond - Metrolina Neurological Associates</name>
      <address>
        <city>Indian Land</city>
        <state>South Carolina</state>
        <zip>29707</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Texas Movement Disorders Institute</name>
      <address>
        <city>Bedford</city>
        <state>Texas</state>
        <zip>76021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BTC Network - Neurological Associates of North Texas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Network</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77074</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sentara Neuroscience Institute</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23456</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Evergreen Health - Booth Gardner Parkinson's Care Center</name>
      <address>
        <city>Kirkland</city>
        <state>Washington</state>
        <zip>98034</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Physicians &amp; Surgeons, Inc. dba Marshall Health</name>
      <address>
        <city>Huntington</city>
        <state>West Virginia</state>
        <zip>25701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Camilleri M, Subramanian T, Pagan F, Isaacson S, Gil R, Hauser RA, Feldman M, Goldstein M, Kumar R, Truong D, Chhabria N, Walter BL, Eskenazi J, Riesenberg R, Burdick D, Tse W, Molho E, Robottom B, Bhatia P, Kadimi S, Klos K, Shprecher D, Marquez-Mendoza O, Hidalgo G, Grill S, Li G, Mandell H, Hughes M, Stephenson S, Vandersluis J, Pfeffer M, Duker A, Shivkumar V, Kinney W, MacDougall J, Zasloff M, Barbut D. Oral ENT-01 Targets Enteric Neurons to Treat Constipation in Parkinson Disease : A Randomized Controlled Trial. Ann Intern Med. 2022 Dec;175(12):1666-1674. doi: 10.7326/M22-1438. Epub 2022 Nov 8. Erratum In: Ann Intern Med. 2023 Jan;176(1):144.</citation>
    <PMID>36343348</PMID>
  </results_reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>June 27, 2023</last_update_submitted>
  <last_update_submitted_qc>June 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2023</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>Parkinson Disease</mesh_term>
    <mesh_term>Constipation</mesh_term>
  </condition_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/NCT03781791
org study id: ENT-01-030
nct id: NCT03781791
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will be conducted as a multi-center, randomized, double-blind, placebo-controlled
      study. Approximately 72 patients will be randomized 3:1 to treatment or placebo, with
      approximately 54 patients allocated to receive the active investigational product and
      approximately 18 patients allocated to receive placebo.

      - Study Update-

      Amendment 3 - In this amendment, an additional 80 patients (approximately) will be randomized
      1:1 to treatment or placebo (double-blind) with approximately 40 subjects allocated to each
      group.
The study will be conducted on an out-patient basis. Each patient will have 6 visits to the
      clinic: a screening visit, a randomization visit, 3 follow up visits, and 1 end of study
      visit.

      Patient randomization will be stratified based upon the baseline weekly complete spontaneous
      bowel movement rate (CSBM) established during the screening period. Patients will be allowed
      to adjust their dosing, based upon protocol specifications. Rescue medications will be
      provided to all patients to ensure they move their bowels on a regular basis.

      Patients will also be asked to participate in up to 2 sub-studies: a pk study and/or a stool
      microbiome study. The first 20 patients to consent to the pk study will have additional blood
      samples taken at randomization and at 2 follow up visits. The first 20 patients to consent to
      the stool microbiome study will provide stool samples at randomization and at 2 follow up
      visits.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Incidence of Treatment Related Adverse Events-Safety Endpoint
time frame: Through Study treatment up to 10 weeks
description: The number of treatment related adverse events as reported and assessed by NCI CTCAE v.4.3.
measure: Incidence of Treatment Related Adverse Event-Tolerability Endpoints
time frame: Through Study treatment Dosing Period up to 10 weeks
description: The number of treatment related adverse events as reported and assessed by NCI CTCAE v.4.3.
measure: Change in baseline weekly CSBM-Primary Efficacy Endpoint
time frame: Through Study Treatment Dosing Period up to 10 weeks
description: Change from participant's weekly CSBM baseline rate during treatment fixed Dose period.
measure: Change in participant constipation severity from baseline-Secondary Efficacy Endpoints
time frame: Through Study Treatment Dosing Period up to 10 weeks
description: Participant reported change from baseline as assessed according to Bristol Stool rating scale (0-5) of increasing severity of ease of bowel evacuation.
measure: Change in baseline stool Microbiome - Exploratory Outcome
time frame: Through Study Treatment Dosing Period and Completion up to 24 weeks
description: Collection of participant baseline intestinal microbiome condition as observed in stool to on treatment related effect of ENT-01 on stool microbiome
arm group label: Active Treatment
arm group type: Experimental
description: ENT-01 tablet will be taken once daily by mouth.
arm group label: Placebo Treatment
arm group type: Placebo Comparator
description: Placebo tablet will be taken once daily by mouth.
intervention type: Drug
intervention name: Active Investigational Treatment ENT-01
description: ENT-01 will be administered in tablet form, once daily.
arm group label: Active Treatment
other name: ENT-01
intervention type: Drug
intervention name: Placebo Treatment
description: Placebo will be administered in tablet form, once daily.
arm group label: Placebo Treatment
criteria: 
gender: All
minimum age: 30 Years
maximum age: 90 Years
healthy volunteers: No
last name: Michael Zasloff, MD PhD
role: Study Chair
affiliation: Enterin Inc.
last name: Denise Barbut, MD, FRCP
role: Study Director
affiliation: Enterin Inc.
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country: United States
citation: Camilleri M, Subramanian T, Pagan F, Isaacson S, Gil R, Hauser RA, Feldman M, Goldstein M, Kumar R, Truong D, Chhabria N, Walter BL, Eskenazi J, Riesenberg R, Burdick D, Tse W, Molho E, Robottom B, Bhatia P, Kadimi S, Klos K, Shprecher D, Marquez-Mendoza O, Hidalgo G, Grill S, Li G, Mandell H, Hughes M, Stephenson S, Vandersluis J, Pfeffer M, Duker A, Shivkumar V, Kinney W, MacDougall J, Zasloff M, Barbut D. Oral ENT-01 Targets Enteric Neurons to Treat Constipation in Parkinson Disease : A Randomized Controlled Trial. Ann Intern Med. 2022 Dec;175(12):1666-1674. doi: 10.7326/M22-1438. Epub 2022 Nov 8. Erratum In: Ann Intern Med. 2023 Jan;176(1):144.
PMID: 36343348
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Constipation
sharing ipd: No