<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/NCT04483479</url>
  </required_header>
  <id_info>
    <org_study_id>ENT-01-2b-20-02</org_study_id>
    <nct_id>NCT04483479</nct_id>
  </id_info>
  <brief_title>Orally Administered ENT-01 for Parkinson's Disease-Related Constipation Follow-on Safety &quot;Roll-over&quot; Study (Rollover)</brief_title>
  <acronym>Rollover</acronym>
  <official_title>A Multicenter, Non-Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Orally Administered ENT-01 in Improving Constipation and Neurologic Symptoms in Patients With Parkinson's Disease and Constipation Over a 14-week Period</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 an open-label safety follow-on to a multi-center,&#xD;
      double-blind, randomized study. All subjects who participated in the randomized study will be&#xD;
      offered participation in this unblinded, single-arm, safety study. Approximately 50 subjects&#xD;
      will be entered into the study and ENT-01 will be administered daily in escalating doses&#xD;
      followed by a fixed dose for 12 weeks. Each subject will participate for approximately 20&#xD;
      weeks; dosing duration will be approximately 14 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be conducted on an out-patient or in-patient basis with visits performed at&#xD;
      the screening visit, at 6 and 12 weeks, and at the end of the 6th week of the wash-out period&#xD;
      (end of study).&#xD;
&#xD;
      The dose escalation period will last up to 20 days, the fixed dose period will last 12 weeks,&#xD;
      and the wash-out period will last 6 weeks.&#xD;
&#xD;
      Subjects will begin dosing at the same dose level they were stratified to in the ENT-01-030&#xD;
      randomized study (i.e., starting at either 3 tablets or 6 tablets,) and escalate up to a&#xD;
      pro-kinetic dose or a maximum dose of 250mg.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Poor recruitment/retention due to the pandemic. Data was not analyzed due to early termination.&#xD;
  </why_stopped>
  <start_date type="Actual">July 30, 2020</start_date>
  <completion_date type="Actual">February 17, 2022</completion_date>
  <primary_completion_date type="Actual">February 17, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a Phase 2b, non-randomized, open-label study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment Related Adverse Events - Primary SAFETY Endpoint</measure>
    <time_frame>Through study treatment and completion up to 14 weeks</time_frame>
    <description>The number of treatment related adverse events as evaluated with subject report, vital signs, chemical chemistry and electrocardiograms (EKG)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Treatment Related Recurrent Vomiting - TOLERABILITY Endpoints</measure>
    <time_frame>Through study treatment and completion up to 14 weeks</time_frame>
    <description>The number of treatment related episodes of recurrent vomiting defined as 3-5 episodes of vomiting within 24 hours.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Treatment Related Recurrent Diarrhea - TOLERABILITY Endpoints</measure>
    <time_frame>Through study treatment and completion up to 14 weeks</time_frame>
    <description>The number of treatment related episodes of recurrent diarrhea defined as 7 episodes of diarrhea within 24 hours for 2 consecutive days.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Treatment Related Dizziness - TOLERABILITY Endpoints</measure>
    <time_frame>Through study treatment and completion up to 14 weeks</time_frame>
    <description>The number of treatment related episodes of dizziness defined as lightheadedness or fainting on rising from lying to sitting or standing and severe enough to require non-urgent medical intervention within 24 hours.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Baseline Weekly CSBM Rate - Primary EFFICACY Endpoint</measure>
    <time_frame>Through study treatment up to 12 weeks</time_frame>
    <description>Change from baseline in weekly CSBM rate during the 12 weeks of treatment over baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>MDS-UPDRS - Secondary EFFICACY Endpoints</measure>
    <time_frame>Through study treatment up to 12 weeks</time_frame>
    <description>Change from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score at the end of the 12-week fixed dose period. Score range: 0-272. Higher score indicates increased disease severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MMSE - Secondary EFFICACY Endpoints</measure>
    <time_frame>Through study treatment up to 12 weeks</time_frame>
    <description>Change from baseline in cognition as assessed by the Mini-Mental State Examination (MMSE) at the 12-week fixed dose period. Score range: 0-30. Below the score of 24, lower score indicates an increasing severity of cognitive impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SAPS-PD - Secondary EFFICACY Endpoints</measure>
    <time_frame>Through study treatment up to 12 weeks</time_frame>
    <description>Change from baseline in psychosis as assessed by the Scale for the Assessment of Positive Symptoms for Parkinson's Disease Psychosis (SAPS-PD) score at the 12-week fixed dose period. Score range: 0-45. Higher score indicates increased presence of psychosis.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Parkinson Disease</condition>
  <condition>Constipation</condition>
  <arm_group>
    <arm_group_label>Active Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Orally Administered ENT-01 25mg Tablet Once Daily (Dose dependent on ENT-01-030 dose level stratification)</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 in escalating doses followed by a fixed-dose for 12 weeks.</description>
    <arm_group_label>Active Treatment</arm_group_label>
    <other_name>ENT-01</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. All subjects who participated in the randomized study ENT-01-030 (KARMET Stage 2&#xD;
             Extension subjects) and who completed the dosing period.&#xD;
&#xD;
          2. Subjects aged 30-90 years at the time of screening for the ENT-01-030 study, both&#xD;
             genders&#xD;
&#xD;
          3. Subjects must provide informed consent and be willing and able to comply with study&#xD;
             procedures.&#xD;
&#xD;
          4. Subjects must be able to read, understand, and accurately record data into the diary&#xD;
             to guarantee full participation in the study.&#xD;
&#xD;
          5. 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;
          6. 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. Unable to withdraw proton pump inhibitors.&#xD;
&#xD;
          3. 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;
          4. Diagnosis of secondary constipation beyond that of Parkinson's disease.&#xD;
&#xD;
          5. A compromised gastrointestinal system which includes:&#xD;
&#xD;
               -  Structural, metabolic, or functional GI diseases or disorders.&#xD;
&#xD;
               -  Acute GI illness within 2 weeks of the screening visit.&#xD;
&#xD;
               -  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;
          6. 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;
          7. On treatment with intra-jejunal dopamine or carbidopa/levodopa (i.e. Duopa).&#xD;
&#xD;
          8. Subjects starting a new Parkinson's disease medication or modifying an existing&#xD;
             medication within 2 weeks prior to enrollment.&#xD;
&#xD;
          9. Unable to maintain a stable diet regimen.&#xD;
&#xD;
         10. Subjects with a cognitive impairment that preclude them from understanding the&#xD;
             informed consent.&#xD;
&#xD;
         11. Subjects placed under legal guardianship.&#xD;
&#xD;
         12. History of excessive alcohol use or substance abuse.&#xD;
&#xD;
         13. Any clinically significant abnormalities on screening laboratories or physical&#xD;
             examination requiring further evaluation or treatment.&#xD;
&#xD;
         14. Females who are pregnant or breastfeeding.&#xD;
&#xD;
         15. Subject or caregiver unable to administer daily oral dosing of study drug.&#xD;
&#xD;
         16. Participation in a non-Enterin investigational drug trial within the month prior to&#xD;
             dosing in the present study.&#xD;
&#xD;
         17. 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>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>SC3 Research - Pasadena</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91105</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>Georgetown Universtiy, Department of Neurology</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>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>USF Health Byrd Parkinson's Disease Movement Disorders Center of Excellence</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Premiere Research Institute at Palm Beach Neurology</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33407</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>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>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44095</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>Penn State University</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</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>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>June 28, 2023</last_update_submitted>
  <last_update_submitted_qc>June 28, 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/NCT04483479
org study id: ENT-01-2b-20-02
nct id: NCT04483479
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will be conducted as an open-label safety follow-on to a multi-center,
      double-blind, randomized study. All subjects who participated in the randomized study will be
      offered participation in this unblinded, single-arm, safety study. Approximately 50 subjects
      will be entered into the study and ENT-01 will be administered daily in escalating doses
      followed by a fixed dose for 12 weeks. Each subject will participate for approximately 20
      weeks; dosing duration will be approximately 14 weeks.
The study will be conducted on an out-patient or in-patient basis with visits performed at
      the screening visit, at 6 and 12 weeks, and at the end of the 6th week of the wash-out period
      (end of study).

      The dose escalation period will last up to 20 days, the fixed dose period will last 12 weeks,
      and the wash-out period will last 6 weeks.

      Subjects will begin dosing at the same dose level they were stratified to in the ENT-01-030
      randomized study (i.e., starting at either 3 tablets or 6 tablets,) and escalate up to a
      pro-kinetic dose or a maximum dose of 250mg.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a Phase 2b, non-randomized, open-label study.
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment Related Adverse Events - Primary SAFETY Endpoint
time frame: Through study treatment and completion up to 14 weeks
description: The number of treatment related adverse events as evaluated with subject report, vital signs, chemical chemistry and electrocardiograms (EKG)
measure: Incidence of Treatment Related Recurrent Vomiting - TOLERABILITY Endpoints
time frame: Through study treatment and completion up to 14 weeks
description: The number of treatment related episodes of recurrent vomiting defined as 3-5 episodes of vomiting within 24 hours.
measure: Incidence of Treatment Related Recurrent Diarrhea - TOLERABILITY Endpoints
time frame: Through study treatment and completion up to 14 weeks
description: The number of treatment related episodes of recurrent diarrhea defined as 7 episodes of diarrhea within 24 hours for 2 consecutive days.
measure: Incidence of Treatment Related Dizziness - TOLERABILITY Endpoints
time frame: Through study treatment and completion up to 14 weeks
description: The number of treatment related episodes of dizziness defined as lightheadedness or fainting on rising from lying to sitting or standing and severe enough to require non-urgent medical intervention within 24 hours.
measure: Change in Baseline Weekly CSBM Rate - Primary EFFICACY Endpoint
time frame: Through study treatment up to 12 weeks
description: Change from baseline in weekly CSBM rate during the 12 weeks of treatment over baseline.
measure: MDS-UPDRS - Secondary EFFICACY Endpoints
time frame: Through study treatment up to 12 weeks
description: Change from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score at the end of the 12-week fixed dose period. Score range: 0-272. Higher score indicates increased disease severity.
measure: MMSE - Secondary EFFICACY Endpoints
time frame: Through study treatment up to 12 weeks
description: Change from baseline in cognition as assessed by the Mini-Mental State Examination (MMSE) at the 12-week fixed dose period. Score range: 0-30. Below the score of 24, lower score indicates an increasing severity of cognitive impairment.
measure: SAPS-PD - Secondary EFFICACY Endpoints
time frame: Through study treatment up to 12 weeks
description: Change from baseline in psychosis as assessed by the Scale for the Assessment of Positive Symptoms for Parkinson's Disease Psychosis (SAPS-PD) score at the 12-week fixed dose period. Score range: 0-45. Higher score indicates increased presence of psychosis.
arm group label: Active Treatment
arm group type: Experimental
description: Orally Administered ENT-01 25mg Tablet Once Daily (Dose dependent on ENT-01-030 dose level stratification)
intervention type: Drug
intervention name: Active Investigational Treatment ENT-01
description: ENT-01 will be administered in tablet form, once daily in escalating doses followed by a fixed-dose for 12 weeks.
arm group label: Active Treatment
other name: ENT-01
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.
facility: 
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country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Constipation
sharing ipd: No