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

Parkinson's Disease Clinical Trial

— RASMET  

Official title:

A Multi-Center, Single-Dose, Multiple-Dose, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered ENT-01 for the Treatment of Parkinson's Disease Related Constipation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03047629
• Other study ID #: ENT-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 11, 2017
• Est. completion date: June 14, 2018

Study information

• Verified date: December 2023
• Source: Enterin Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 14, 2018
• Est. primary completion date: April 25, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 86 Years

Eligibility

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

Related Conditions & MeSH terms

• Constipation
• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• 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.

Other:
• Placebo
Daily dosing with a placebo

Locations

Country	Name	City	State
United States	Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida
United States	Riverhills Healthcare, Inc.	Cincinnati	Ohio
United States	Parkinson's & Movement Disorders Center, UH Cleveland Medical Center	Cleveland	Ohio
United States	Rocky Mountain Movement Disorders Center, PC	Englewood	Colorado
United States	Quest Research Institute	Farmington Hills	Michigan
United States	Penn State Health, Department of Neurology	Hershey	Pennsylvania
United States	Neuroscience Research, University of Florida Jacksonville	Jacksonville	Florida
United States	Keck Hospital of University of Southern California	Los Angeles	California
United States	Movement Disorders Division, Mt. Sinai School of Medicine	New York	New York
United States	Thomas Jefferson University, Department of Neurology	Philadelphia	Pennsylvania
United States	MEDSOL Clinical Research	Port Charlotte	Florida
United States	Suncoast Neuroscience Associates, Inc	Saint Petersburg	Florida
United States	Sarasota Memory Hospital Clinical Research Ctr.	Sarasota	Florida
United States	USF Health Byrd Parkinson's Disease Movement Disorders Center of Excellence	Tampa	Florida
United States	Georgetown Universtiy, Department of Neurology	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Enterin Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events.	Specific treatment related events of recurrent vomiting, recurrent diarrhea, abdominal pain, and hypotension will be assessed with respect to grade and frequency of occurrence.	Through study completion, up to 11 weeks
Secondary	Frequency of Bowel Movements	The frequency of spontaneous bowel movements will be assessed at each dose across the study population and compared to baseline measures.	Through study completion, up to 11 weeks