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

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ClinicalTrials.gov Identifier: NCT03047629
Recruitment Status : Active, not recruiting
First Posted : February 9, 2017
Last Update Posted : March 23, 2018
Sponsor:
Information provided by (Responsible Party):
Enterin Inc.

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.

Condition or disease Intervention/treatment Phase
Parkinson's Disease Constipation Drug: ENT-01 Other: Placebo Phase 1 Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 1 is a single group; Phase 2 will begin subsequent to the safe completion of Phase 1. Phase 2 patients will undergo randomization for parallel study during one period of observation of the course of the study phase.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : May 15, 2017
Estimated Primary Completion Date : April 2018
Estimated Study Completion Date : April 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ENT-01
ENT-01 at a to-be-determined dose taken by mouth every day upon awakening.
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.

Placebo Comparator: Placebo Comparator
Placebo to be taken by mouth every day upon awakening
Other: Placebo
Daily dosing with a placebo




Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by common terminology criteria for adverse events. [ Time Frame: Through study completion, up to 11 weeks ]
    Specific treatment related events of recurrent vomiting, recurrent diarrhea, abdominal pain, and hypotension will be assessed with respect to grade and frequency of occurrence.


Secondary Outcome Measures :
  1. Frequency of bowel movements [ Time Frame: Through study completion, up to 11 weeks ]
    The frequency of spontaneous bowel movements will be assessed at each dose across the study population and compared to baseline measures.



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Ages Eligible for Study:   30 Years to 86 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03047629


Locations
United States, California
Keck Hospital of University of Southern California
Los Angeles, California, United States, 90033
United States, Colorado
Rocky Mountain Movement Disorders Center, PC
Englewood, Colorado, United States, 80113
United States, District of Columbia
Georgetown Universtiy, Department of Neurology
Washington, District of Columbia, United States, 20007
United States, Florida
Parkinson's Disease and Movement Disorders Center of Boca Raton
Boca Raton, Florida, United States, 33486
Neuroscience Research, University of Florida Jacksonville
Jacksonville, Florida, United States, 32209
MEDSOL Clinical Research
Port Charlotte, Florida, United States, 33952
Suncoast Neuroscience Associates, Inc
Saint Petersburg, Florida, United States, 33713
Sarasota Memory Hospital Clinical Research Ctr.
Sarasota, Florida, United States, 34239
USF Health Byrd Parkinson's Disease Movement Disorders Center of Excellence
Tampa, Florida, United States, 33613
United States, Michigan
Quest Research Institute
Farmington Hills, Michigan, United States, 48334
United States, New York
Movement Disorders Division, Mt. Sinai School of Medicine
New York, New York, United States, 10029
United States, Ohio
Riverhills Healthcare, Inc.
Cincinnati, Ohio, United States, 45212
Parkinson's & Movement Disorders Center, UH Cleveland Medical Center
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Penn State Health, Department of Neurology
Hershey, Pennsylvania, United States, 17033
Thomas Jefferson University, Department of Neurology
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Enterin Inc.
Investigators
Study Chair: Denise Barbut, MD FRCP Enterin Inc.
Principal Investigator: Steven Frucht, MD NYU, Langone Health
Principal Investigator: Robert Hauser, MD MBA University of South Florida

Responsible Party: Enterin Inc.
ClinicalTrials.gov Identifier: NCT03047629     History of Changes
Other Study ID Numbers: ENT-01
First Posted: February 9, 2017    Key Record Dates
Last Update Posted: March 23, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Anonymized data may be shared with other clinical researchers outside of this study that are involved in similar research at non-participating institutions.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Enterin Inc.:
non-motor symptoms

Additional relevant MeSH terms:
Parkinson Disease
Constipation
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Signs and Symptoms, Digestive
Signs and Symptoms