Orally Administered ENT-01 for Parkinson's Disease-Related Constipation Follow-on Safety "Roll-over" Study (Rollover) (Rollover)

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

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.

Study Overview

• Status: Terminated
• Conditions: Parkinson Disease; Constipation
• Intervention / Treatment: Drug: Active Investigational Treatment ENT-01

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Fountain Valley, California, United States, 92708
      • The Parkinson's and Movement Disorder Institute
    • Pasadena, California, United States, 91105
      • SC3 Research - Pasadena
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Movement Disorders Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown Universtiy, Department of Neurology
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center of Boca Raton
    • Port Charlotte, Florida, United States, 33980
      • Parkinson's Disease Treatment Center of SWFL
    • Sarasota, Florida, United States, 34239
      • Intercoastal Medical Group
    • Tampa, Florida, United States, 33613
      • USF Health Byrd Parkinson's Disease Movement Disorders Center of Excellence
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute at Palm Beach Neurology
  • New Hampshire
    • Lebanon, New Hampshire, United States, 13756
      • Dartmouth Hitchcock Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • New York, New York, United States, 10029
      • Icahn School Of Medicine At Mount Sinai
  • Ohio
    • Cleveland, Ohio, United States, 44095
      • Cleveland Clinic
    • Toledo, Ohio, United States, 43614
      • University of Toledo Medical Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State University
  • Washington
    • Kirkland, Washington, United States, 98034
      • Evergreen Health - Booth Gardner Parkinson's Care Center
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • University Physicians & Surgeons, Inc. dba Marshall Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. All subjects who participated in the randomized study ENT-01-030 (KARMET Stage 2 Extension subjects) and who completed the dosing period.
2. Subjects aged 30-90 years at the time of screening for the ENT-01-030 study, both genders
3. Subjects must provide informed consent and be willing and able to comply with study procedures.
4. Subjects must be able to read, understand, and accurately record data into the diary to guarantee full participation in the study.
5. Female subjects must have negative serum or urine pregnancy tests and must not be lactating. For females able to bear children, a hormonal (i.e., oral, implantable, or injectable) and single-barrier method, or a double-barrier method of birth control must be used throughout the study. A vasectomized partner will be allowed as one in conjunction with another single-barrier method.
6. Female subjects unable to bear children must have this documented in the CRF (i.e., tubal ligation, hysterectomy, or postmenopausal [defined as a minimum of one year since the last menstrual period]). Post-menopausal status will be confirmed by follicle stimulating hormone (FSH) in women less than 60 years of age.

Exclusion Criteria:

1. Unable or unwilling to provide informed consent or to comply with study procedures.
2. Unable to withdraw proton pump inhibitors.
3. Unable or unwilling to withdraw from laxatives, opiates, clonazepam, or any medications which may cause constipation 2 weeks prior to the dose adjustment period and throughout the rest of the study.
4. Diagnosis of secondary constipation beyond that of Parkinson's disease.

5. A compromised gastrointestinal system which includes:

   • Structural, metabolic, or functional GI diseases or disorders.
   • Acute GI illness within 2 weeks of the screening visit.
   • History of major GI surgery within 30 days of the screening visit (a history of cholecystectomy, polypectomy, hernia repair or appendicectomy are not exclusionary as long as they were performed more than 30 days before the screening visit).
6. Neurological disorder other than Parkinson's disease that in the opinion of the investigator might interfere with the conduct of the study.
7. On treatment with intra-jejunal dopamine or carbidopa/levodopa (i.e. Duopa).
8. Subjects starting a new Parkinson's disease medication or modifying an existing medication within 2 weeks prior to enrollment.
9. Unable to maintain a stable diet regimen.
10. Subjects with a cognitive impairment that preclude them from understanding the informed consent.
11. Subjects placed under legal guardianship.
12. History of excessive alcohol use or substance abuse.
13. Any clinically significant abnormalities on screening laboratories or physical examination requiring further evaluation or treatment.
14. Females who are pregnant or breastfeeding.
15. Subject or caregiver unable to administer daily oral dosing of study drug.
16. Participation in a non-Enterin investigational drug trial within the month prior to dosing in the present study.
17. Any other reason, which in the opinion of the investigator would confound proper interpretation of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Treatment; Orally Administered ENT-01 25mg Tablet Once Daily (Dose dependent on ENT-01-030 dose level stratification)	Drug: Active Investigational Treatment ENT-01; ENT-01 will be administered in tablet form, once daily in escalating doses followed by a fixed-dose for 12 weeks.; Other Names: ENT-01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Related Adverse Events	Number of participants with Treatment Related Adverse Events	Through study treatment and completion up to 14 weeks
Number of Participants With Treatment Related Recurrent Vomiting	The number of participants with treatment related episodes of recurrent vomiting defined as 3-5 episodes of vomiting within 24 hours	Through study treatment and completion up to 14 weeks
Number of Participants With Treatment Related Recurrent Diarrhea	The number of participants with treatment related episodes of recurrent diarrhea defined as 7 episodes of diarrhea within 24 hours for 2 consecutive days	Through study treatment and completion up to 14 weeks
Number of Participants With Treatment Related Dizziness	The number of participants with 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	Through study treatment and completion up to 14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MDS-UPDRS - Secondary EFFICACY Endpoints	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.	Through study treatment up to 12 weeks
MMSE - Secondary EFFICACY Endpoints	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.	Through study treatment up to 12 weeks
SAPS-PD - Secondary EFFICACY Endpoints	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.	Through study treatment up to 12 weeks

Collaborators and Investigators

• Sponsor: Enterin Inc.
• Investigators: Study Chair: Michael Zasloff, MD, PhD, Enterin Inc.; Study Director: Denise Barbut, MD, FRCP, Enterin Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2020
• Primary Completion (Actual): February 17, 2022
• Study Completion (Actual): February 17, 2022

Study Registration Dates

• First Submitted: July 20, 2020
• First Submitted That Met QC Criteria: July 22, 2020
• First Posted (Actual): July 23, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Digestive; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Constipation
• Other Study ID Numbers: ENT-01-2b-20-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No