## Protocol Section
### Identification Module
**NCT ID:** NCT04483479

**Acronym:** Rollover

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

**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

#### Organization Study ID Info
**ID:** ENT-01-2b-20-02
#### Organization
**Class:** INDUSTRY
**Full Name:** Enterin Inc.
### Status Module
#### Completion Date
**Date:** 2022-02-17

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-03-19

**Type:** ACTUAL

**Last Update Submit Date:** 2024-02-20

**Overall Status:** TERMINATED

#### Primary Completion Date
**Date:** 2022-02-17

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2024-03-19

**Type:** ACTUAL

**Results First Submit Date:** 2023-10-03

**Results First Submit QC Date:** 2024-02-20

#### Start Date
**Date:** 2020-07-30

**Type:** ACTUAL

**Status Verified Date:** 2024-02

#### Study First Post Date
**Date:** 2020-07-23
**Type:** ACTUAL
**Study First Submit Date:** 2020-07-20
**Study First Submit QC Date:** 2020-07-22
**Why Stopped:** Poor recruitment/retention due to the pandemic. Data was not analyzed due to early termination.
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Enterin Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** 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.

**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.

### Conditions Module

**Conditions:**

- Parkinson Disease

- Constipation

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** This is a Phase 2b, non-randomized, open-label study.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 27

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Orally Administered ENT-01 25mg Tablet Once Daily (Dose dependent on ENT-01-030 dose level stratification)

**Intervention Names:**

- Drug: Active Investigational Treatment ENT-01

**Label:** Active Treatment

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Active Treatment

**Description:** ENT-01 will be administered in tablet form, once daily in escalating doses followed by a fixed-dose for 12 weeks.

**Name:** Active Investigational Treatment ENT-01

**Other Names:**

- ENT-01

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Number of participants with Treatment Related Adverse Events

**Measure:** Number of Participants With Treatment Related Adverse Events

**Time Frame:** Through study treatment and completion up to 14 weeks

**Description:** The number of participants with treatment related episodes of recurrent vomiting defined as 3-5 episodes of vomiting within 24 hours

**Measure:** Number of Participants With Treatment Related Recurrent Vomiting

**Time Frame:** Through study treatment and completion up to 14 weeks

**Description:** The number of participants with treatment related episodes of recurrent diarrhea defined as 7 episodes of diarrhea within 24 hours for 2 consecutive days

**Measure:** Number of Participants With Treatment Related Recurrent Diarrhea

**Time Frame:** Through study treatment and completion up to 14 weeks

**Description:** 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

**Measure:** Number of Participants With Treatment Related Dizziness

**Time Frame:** Through study treatment and completion up to 14 weeks

### Eligibility Module

**Eligibility Criteria:** 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.

**Maximum Age:** 90 Years

**Minimum Age:** 30 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Fountain Valley

**Country:** United States

**Facility:** The Parkinson's and Movement Disorder Institute

**State:** California

**Zip:** 92708

**Location 2:**

**City:** Pasadena

**Country:** United States

**Facility:** SC3 Research - Pasadena

**State:** California

**Zip:** 91105

**Location 3:**

**City:** Englewood

**Country:** United States

**Facility:** Rocky Mountain Movement Disorders Center

**State:** Colorado

**Zip:** 80113

**Location 4:**

**City:** Washington

**Country:** United States

**Facility:** Georgetown Universtiy, Department of Neurology

**State:** District of Columbia

**Zip:** 20007

**Location 5:**

**City:** Atlantis

**Country:** United States

**Facility:** JEM Research Institute

**State:** Florida

**Zip:** 33462

**Location 6:**

**City:** Boca Raton

**Country:** United States

**Facility:** Parkinson's Disease and Movement Disorders Center of Boca Raton

**State:** Florida

**Zip:** 33486

**Location 7:**

**City:** Port Charlotte

**Country:** United States

**Facility:** Parkinson's Disease Treatment Center of SWFL

**State:** Florida

**Zip:** 33980

**Location 8:**

**City:** Sarasota

**Country:** United States

**Facility:** Intercoastal Medical Group

**State:** Florida

**Zip:** 34239

**Location 9:**

**City:** Tampa

**Country:** United States

**Facility:** USF Health Byrd Parkinson's Disease Movement Disorders Center of Excellence

**State:** Florida

**Zip:** 33613

**Location 10:**

**City:** West Palm Beach

**Country:** United States

**Facility:** Premiere Research Institute at Palm Beach Neurology

**State:** Florida

**Zip:** 33407

**Location 11:**

**City:** Lebanon

**Country:** United States

**Facility:** Dartmouth Hitchcock Medical Center

**State:** New Hampshire

**Zip:** 13756

**Location 12:**

**City:** Albany

**Country:** United States

**Facility:** Albany Medical College

**State:** New York

**Zip:** 12208

**Location 13:**

**City:** New York

**Country:** United States

**Facility:** Icahn School of Medicine at Mount Sinai

**State:** New York

**Zip:** 10029

**Location 14:**

**City:** Cleveland

**Country:** United States

**Facility:** Cleveland Clinic

**State:** Ohio

**Zip:** 44095

**Location 15:**

**City:** Toledo

**Country:** United States

**Facility:** University of Toledo Medical Center

**State:** Ohio

**Zip:** 43614

**Location 16:**

**City:** Hershey

**Country:** United States

**Facility:** Penn State University

**State:** Pennsylvania

**Zip:** 17033

**Location 17:**

**City:** Kirkland

**Country:** United States

**Facility:** Evergreen Health - Booth Gardner Parkinson's Care Center

**State:** Washington

**Zip:** 98034

**Location 18:**

**City:** Huntington

**Country:** United States

**Facility:** University Physicians & Surgeons, Inc. dba Marshall Health

**State:** West Virginia

**Zip:** 25701

#### Overall Officials

**Official 1:**

**Affiliation:** Enterin Inc.

**Name:** Michael Zasloff, MD, PhD

**Role:** STUDY_CHAIR

**Official 2:**

**Affiliation:** Enterin Inc.

**Name:** Denise Barbut, MD, FRCP

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Document Section

### Large Document Module

#### Large Docs

- Date: 2020-06-30

- Filename: Prot_SAP_001.pdf

- Has ICF: False

- Has Protocol: True

- Has SAP: True

- Label: Study Protocol and Statistical Analysis Plan

- Size: 598378

- Type Abbrev: Prot_SAP

- Upload Date: 2023-11-07T10:40

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020734

- Term: Parkinsonian Disorders

- ID: D000001480

- Term: Basal Ganglia Diseases

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000009069

- Term: Movement Disorders

- ID: D000080874

- Term: Synucleinopathies

- ID: D000019636

- Term: Neurodegenerative Diseases

- ID: D000012817

- Term: Signs and Symptoms, Digestive

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

### Condition Browse Module - Browse Leaves

- ID: M6472

- Name: Constipation

- Relevance: HIGH

- As Found: Constipation

- ID: M13213

- Name: Parkinson Disease

- Relevance: HIGH

- As Found: Parkinson's Disease

- ID: M22494

- Name: Parkinsonian Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M25603

- Name: Ganglion Cysts

- Relevance: LOW

- As Found: Unknown

- ID: M16358

- Name: Synovial Cyst

- Relevance: LOW

- As Found: Unknown

- ID: M4774

- Name: Basal Ganglia Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12029

- Name: Movement Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M2217

- Name: Synucleinopathies

- Relevance: LOW

- As Found: Unknown

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15622

- Name: Signs and Symptoms, Digestive

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000010300

- Term: Parkinson Disease

- ID: D000003248

- Term: Constipation

### Misc Info Module

#### Submission Tracking

##### First MCP Info

###### Post Date

- Date: 2023-10-27

- Type: ACTUAL

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

#### Event Groups

**Group ID:** EG000

**Title:** Active Treatment

**Deaths Num At Risk:** 27

**Description:** Orally Administered ENT-01 25mg Tablet Once Daily (Dose dependent on ENT-01-030 dose level stratification)

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.

**ID:** EG000

**Other Num Affected:** 24

**Other Num at Risk:** 27

**Serious Number At Risk:** 27

**Title:** Active Treatment

**Frequency Threshold:** 5

#### Other Events

**Term:** Nausea

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA (Unspecified)

**Term:** Vomiting

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA (Unspecified)

**Term:** Diarrhoea

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA (Unspecified)

**Term:** Tremors

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA (Unspecified)

**Term:** Weight Decreased

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA (Unspecified)

**Term:** Dizziness

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Vascular disorders

**Source Vocabulary:** MedDRA (Unspecified)

**Time Frame:** 20 weeks

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 27

**Units:** Participants

### Group

**ID:** BG000

**Title:** Active Treatment

**Description:** Orally Administered ENT-01 25mg Tablet Once Daily (Dose dependent on ENT-01-030 dose level stratification)

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.

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** <=18 years

#### Measurement

**Group ID:** BG000

**Value:** 3

**Category Title:** Between 18 and 65 years

#### Measurement

**Group ID:** BG000

**Value:** 24

**Category Title:** >=65 years

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 9

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 18

**Category Title:** Male

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 3

**Category Title:** Hispanic or Latino

#### Measurement

**Group ID:** BG000

**Value:** 23

**Category Title:** Not Hispanic or Latino

#### Measurement

**Group ID:** BG000

**Value:** 1

**Category Title:** Unknown or Not Reported

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 27

**Class Title:** United States

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 4.63

**Value:** 26.7

**Class Title:** 

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Age, Categorical
**Unit of Measure:** Participants
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Ethnicity (NIH/OMB)
**Unit of Measure:** Participants
### Measure 4
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Region of Enrollment
**Unit of Measure:** Participants
### Measure 5
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** BMI
**Unit of Measure:** KG/m^2
## Results Section - More Information Module
### Certain Agreement
**Restrictive Agreement:** True
### Limitations and Caveats
**Description:** Study was terminated early due to poor recruitment/retention due to the pandemic.
### Point of Contact
**Email:** r.larson@enterininc.com
**Organization:** Enterin
**Phone:** 5054692670
**Title:** Dr. Richard Larson, Chief Medical Officer
## Results Section - Outcome Measures Module
### Outcome Measure 1
### Outcome Measure 2
### Outcome Measure 3
### Outcome Measure 4
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 23
**Title:** 
#### Outcome Measure 2
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 5
**Title:** 
#### Outcome Measure 3
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 8
**Title:** 
#### Outcome Measure 4
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 8
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** Number of participants with Treatment Related Adverse Events
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Reporting Status:** POSTED
**Time Frame:** Through study treatment and completion up to 14 weeks
**Title:** Number of Participants With Treatment Related Adverse Events
**Type:** PRIMARY
**Unit of Measure:** Participants
##### Group
**Description:** Orally Administered ENT-01 25mg Tablet Once Daily (Dose dependent on ENT-01-030 dose level stratification)

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.
**ID:** OG000
**Title:** Active Treatment
#### Outcome Measure 2
**Description:** The number of participants with treatment related episodes of recurrent vomiting defined as 3-5 episodes of vomiting within 24 hours
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Reporting Status:** POSTED
**Time Frame:** Through study treatment and completion up to 14 weeks
**Title:** Number of Participants With Treatment Related Recurrent Vomiting
**Type:** PRIMARY
**Unit of Measure:** Participants
##### Group
**Description:** Orally Administered ENT-01 25mg Tablet Once Daily (Dose dependent on ENT-01-030 dose level stratification)

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.
**ID:** OG000
**Title:** Active Treatment
#### Outcome Measure 3
**Description:** The number of participants with treatment related episodes of recurrent diarrhea defined as 7 episodes of diarrhea within 24 hours for 2 consecutive days
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Reporting Status:** POSTED
**Time Frame:** Through study treatment and completion up to 14 weeks
**Title:** Number of Participants With Treatment Related Recurrent Diarrhea
**Type:** PRIMARY
**Unit of Measure:** Participants
##### Group
**Description:** Orally Administered ENT-01 25mg Tablet Once Daily (Dose dependent on ENT-01-030 dose level stratification)

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.
**ID:** OG000
**Title:** Active Treatment
#### Outcome Measure 4
**Description:** 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
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Reporting Status:** POSTED
**Time Frame:** Through study treatment and completion up to 14 weeks
**Title:** Number of Participants With Treatment Related Dizziness
**Type:** PRIMARY
**Unit of Measure:** Participants
##### Group
**Description:** Orally Administered ENT-01 25mg Tablet Once Daily (Dose dependent on ENT-01-030 dose level stratification)

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.
**ID:** OG000
**Title:** Active Treatment
### Participant Flow Module
#### Group
**Description:** Orally Administered ENT-01 25mg Tablet Once Daily (Dose dependent on ENT-01-030 dose level stratification)

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.
**ID:** FG000
**Title:** Active Treatment
#### Period
**Title:** Overall Study
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 27
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 12
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 15
**Has Results:** True