Evaluation of Safety and Tolerability of ENT-01 for the Treatment of Parkinson's Disease Related Constipation

NCT ID: NCT03047629

Last Updated: 2023-12-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-11
• Study Completion Date: 2018-06-14

Brief Summary

This is a Phase 1/2a study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of an orally-administered medication to relieve symptoms of constipation associated with Parkinson's Disease. Ten patients will be enrolled in Phase 1, and will be studied over an 8-12 week period. Forty patients will be enrolled in Phase 2, and will be studied over an 8-10 week period. All subjects will receive the study drug during one of the observational periods of the study.

Detailed Description

Phase 1 will enroll 10 patients to assess the safety, tolerability, and pharmacokinetics of single escalating doses over a 30-60 day period. The dose-escalation period will be preceded by a 2-week run in period and followed by a 2-week wash-out period.

Phase 2 follow the safe completion of Phase 1. It will enroll 40 patients and is composed of 4 periods of study: 1) a 2-week run-in period, 2) a 3-5 week escalating dose period to identify a prokinetic dose in the initial set of 10 patients, 3) a 1-week period of randomized dosing (placebo versus the previously identified pro-kinetic dose), and 4) a 2-week wash-out period. Pharmacodynamics will be assessed along with safety and tolerability. Relative outcomes will be compared within each patient and across groups for the randomized dosing period.

Frequency of bowel movements and other non-motor symptoms of Parkinson's Disease will be collected over the course of both phases.

Conditions

Parkinson's Disease; Constipation

Keywords

non-motor symptoms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ENT-01

ENT-01 at a to-be-determined dose taken by mouth every day upon awakening.

Group Type: EXPERIMENTAL

ENT-01

Intervention Type: DRUG

Daily dosing with ENT-01. ENT-01 is an orally administered proprietary substance formulated as a small 25mg coated tablet. Dosing will range from 25-200mg, and the dose will be taken upon awakening on an empty stomach with 8oz water simultaneous to dopamine.

Placebo Comparator

Placebo to be taken by mouth every day upon awakening

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Daily dosing with a placebo

Interventions

ENT-01

Daily dosing with ENT-01. ENT-01 is an orally administered proprietary substance formulated as a small 25mg coated tablet. Dosing will range from 25-200mg, and the dose will be taken upon awakening on an empty stomach with 8oz water simultaneous to dopamine.

Intervention Type: DRUG

Placebo

Daily dosing with a placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Parkinson's disease diagnosis confirmed by a neurologist specializing in movement disorders

2. Insufficient criteria for a diagnosis of Irritable Bowel Syndrome

3. Constipation for over 6 months, unresponsive to Milk of Magnesia, and requiring at least weekly treatment using an oral laxative, stool softener, bulking agent, and/or a suppository, and dissatisfaction with current treatment.

4. Body Mass Index is 18-40 kg/m2

5. At least 2 of the Rome IV functional constipation criteria are met

6. Loose stools are rarely present without the use of laxatives

7. Patient is willing and able to sign informed consent and comply with all study procedures

8. Patients must be able to read, understand, and accurately record data into the diary to guarantee full participation in the study

Females only:

9. Must have negative serum or urine pregnancy tests and must not be lactating

10. If of child-bearing age: Must agree to using a hormonal (i.e., oral, implantable, or injectable) and either single- or double-barrier method of birth control throughout the study period. A vasectomized partner will be allowed as one in conjunction with another single-barrier method.

11. If unable to have children: Must have this documented in the case report form (i.e., ubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since last menstrual period]). Post-menopausal status will be confirmed by follicle stimulating hormone 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. Diagnosis of secondary constipation beyond that of PD

3. Structural or metabolic diseases that affect the GI system

4. Functional GI disorder

5. Unable or unwilling to withdraw from taking the following medications 2 weeks prior to the dose-escalation period and throughout the study: Laxatives, opiates, sedatives, hypnotics, anti-histamines, protein pump inhibitors or any medications which may cause constipation

6. History of recent major surgery (within 60 days of screening)

7. Any clinically significant abnormalities on screening laboratories or physical examination as determined by the Investigator

8. Neurological disorder other than PD

9. On treatment with intra-jejunal dopamine

10. Treatment with COMT inhibitors for fewer than 4 weeks (entacapone, tolcapone, Stalevo)

11. Unable to maintain a stable diet regimen

12. Patients with a cognitive impairment that preclude them from understanding the informed consent

13. Patients placed under legal guardianship

14. Acute GI illness within 48 hours of the baseline period

15. History of major GI surgery (e.g. previous abdominal surgery, including cholecystectomy), except that patients with uncomplicated appendectomy are allowed

16. ALT or AST > 1.5 X upper limit of normal (ULN) during screening

17. Females who are pregnant or breastfeeding

18. History of excessive alcohol use or substance abuse

19. Patient or caregiver unable to administer daily oral dosing

20. Participation in an investigational clinical study within the 6 months prior to dosing in the present study

21. Any other reason, which in the opinion of the Investigator would confound proper interpretation of the study

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 86 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Enterin Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Denise Barbut, MD FRCP

Role: STUDY_CHAIR

Enterin Inc.

Steven Frucht, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Robert Hauser, MD MBA

Role: PRINCIPAL_INVESTIGATOR

University of South Florida

Locations

Keck Hospital of University of Southern California

Los Angeles, California, United States

Rocky Mountain Movement Disorders Center, PC

Englewood, Colorado, United States

Georgetown Universtiy, Department of Neurology

Washington D.C., District of Columbia, United States

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, United States

Neuroscience Research, University of Florida Jacksonville

Jacksonville, Florida, United States

MEDSOL Clinical Research

Port Charlotte, Florida, United States

Sarasota Memory Hospital Clinical Research Ctr.

Sarasota, Florida, United States

Suncoast Neuroscience Associates, Inc

St. Petersburg, Florida, United States

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

Tampa, Florida, United States

Quest Research Institute

Farmington Hills, Michigan, United States

Movement Disorders Division, Mt. Sinai School of Medicine

New York, New York, United States

Riverhills Healthcare, Inc.

Cincinnati, Ohio, United States

Parkinson's & Movement Disorders Center, UH Cleveland Medical Center

Cleveland, Ohio, United States

Penn State Health, Department of Neurology

Hershey, Pennsylvania, United States

Thomas Jefferson University, Department of Neurology

Philadelphia, Pennsylvania, United States

Countries

United States

References

Hauser RA, Sutherland D, Madrid JA, Rol MA, Frucht S, Isaacson S, Pagan F, Maddux BN, Li G, Tse W, Walter BL, Kumar R, Kremens D, Lew MF, Ellenbogen A, Oguh O, Vasquez A, Kinney W, Lowery M, Resnick M, Huff N, Posner J, Ballman KV, Harvey BE, Camilleri M, Zasloff M, Barbut D. Targeting neurons in the gastrointestinal tract to treat Parkinson's disease. Clin Park Relat Disord. 2019 Jul 2;1:2-7. doi: 10.1016/j.prdoa.2019.06.001. eCollection 2019.

Reference Type: RESULT

PMID: 34316590 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ENT-01

Identifier Type: -

Identifier Source: org_study_id