Orally Administered ENT-01 for Parkinson's Disease-Related Constipation (KARMET)

Parkinson Disease Clinical Trial

— KARMET  

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate Safety, Tolerability and Efficacy of Orally Administered ENT-01 for the Treatment of Parkinson's Disease-Related Constipation (KARMET)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03781791
• Other study ID #: ENT-01-030
• Status: Completed
• Phase: Phase 2
• Start date: December 10, 2018
• Est. completion date: December 14, 2021

Study information

• Verified date: January 2024
• Source: Enterin Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will be conducted as a multi-center, randomized, double-blind, placebo-controlled study. Approximately 72 patients will be randomized 3:1 to treatment or placebo, with approximately 54 patients allocated to receive the active investigational product and approximately 18 patients allocated to receive placebo.

• Study Update-

Amendment 3 - In this amendment, an additional 80 patients (approximately) will be randomized 1:1 to treatment or placebo (double-blind) with approximately 40 subjects allocated to each group.

Description:

The study will be conducted on an out-patient basis. Each patient will have 6 visits to the clinic: a screening visit, a randomization visit, 3 follow up visits, and 1 end of study visit.

Patient randomization will be stratified based upon the baseline weekly complete spontaneous bowel movement rate (CSBM) established during the screening period. Patients will be allowed to adjust their dosing, based upon protocol specifications. Rescue medications will be provided to all patients to ensure they move their bowels on a regular basis.

Patients will also be asked to participate in up to 2 sub-studies: a pk study and/or a stool microbiome study. The first 20 patients to consent to the pk study will have additional blood samples taken at randomization and at 2 follow up visits. The first 20 patients to consent to the stool microbiome study will provide stool samples at randomization and at 2 follow up visits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: December 14, 2021
• Est. primary completion date: December 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 90 Years

Eligibility

Inclusion Criteria:

1. Subjects aged 30-90 years, both genders

2. Subjects must provide written informed consent and be willing and able to comply with study procedures.

3. Subjects must be diagnosed with Parkinson's Disease defined as the presence of at least three of the following cardinal features, in the absence of alternative explanations or atypical features: rest tremor, rigidity, bradykinesia and/or akinesia, postural and gait abnormalities.

4. There are insufficient criteria for Irritable Bowel Syndrome (IBS)

5. Constipation which has been present for over 6 months and is unresponsive to first line, typically over the counter treatments such as Milk of Magnesia (1g), Miralax (17g in 8 ounces of water) or the equivalent at least once weekly with an inconsistent response over a 6-week period or the subject is dissatisfied with first line treatments.

6. Body mass index (BMI) of 18-40 kg/m2

7. Subjects must fulfill Rome IV criteria for functional constipation which includes 2 or more of the following:

1. Straining during at least 25% of defecations

2. Lumpy or hard stools in at least 25% of defecations

3. Sensation of incomplete evacuation for at least 25% of defecations

4. Sensation of anorectal obstruction/blockage for at least 25% of defecations

5. Manual maneuvers to facilitate at least 25% of defecations (e.g., digital evacuation, support of the pelvic floor)

8. Self-report of fewer than 3 complete spontaneous bowel movements per week

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

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

11. 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.

12. 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. Diagnosis of secondary constipation beyond that of Parkinson's Disease

3. Review of Screening Diaries indicates fewer than 11 days of diary completion and/or 3 or more complete spontaneous bowel movements (CSBM) per week based upon the average CSBM rate reported during the Screening Period

4. A compromised gastrointestinal system which includes:

1. Structural, metabolic, or functional GI diseases or disorders

2. Acute GI illness within 2 weeks of the screening visit

3. 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)

5. 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.

6. Unable or unwilling to withdraw from proton pump inhibitors and antacids at the end of the screening period.

7. Unable or unwilling to withdraw from pimavanserin during the study.

8. Any clinically significant abnormalities on screening laboratories or physical examination requiring further evaluation or treatment.

9. Neurological disorder other than Parkinson's Disease that in the opinion of the investigator might interfere with the conduct of the study.

10. On treatment with intra-jejunal dopamine or carbidopa/levodopa (i.e. Duopa).

11. Subjects starting a new Parkinson's Disease medication or modifying an existing medication within 2 weeks prior to enrollment.

12. Unable to maintain a stable diet regimen.

13. Subjects with a cognitive impairment that preclude them from understanding the informed consent.

14. Subjects placed under legal guardianship.

15. Females who are pregnant or breastfeeding.

16. History of excessive alcohol use or substance abuse.

17. Participation in an investigational drug trial within the month prior to dosing in the present study.

18. Any other reason, which, in the opinion of the investigator, would confound proper interpretation of the study.

Related Conditions & MeSH terms

• Constipation
• Parkinson Disease

Intervention

Drug:
• Active Investigational Treatment ENT-01
ENT-01 will be administered in tablet form, once daily.
• Placebo Treatment
Placebo will be administered in tablet form, once daily.

Locations

Country	Name	City	State
United States	Albany Medical College	Albany	New York
United States	Interspond - The Neuromedical Clinic of Central Louisiana	Alexandria	Louisiana
United States	BTC Network - Community Clinical Research Center	Anderson	Indiana
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	JEM Research Institute	Atlantis	Florida
United States	The NeuroMedical Center, P.C.	Baton Rouge	Louisiana
United States	North Texas Movement Disorders Institute	Bedford	Texas
United States	Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida
United States	Dayton Center for Neurological Disorders	Centerville	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	BTC Network - Neurological Associates of North Texas	Dallas	Texas
United States	Elias Research - Neurology Diagnostics Research	Dayton	Ohio
United States	Parkinson's and Movement Disorders Center of Maryland	Elkridge	Maryland
United States	Rocky Mountain Movement Disorders Center	Englewood	Colorado
United States	Associated Neurologist of Southern CT	Fairfield	Connecticut
United States	The Parkinson's and Movement Disorder Institute	Fountain Valley	California
United States	Neuro Pain Medical Center	Fresno	California
United States	Interspond - Premier Neurology	Greer	South Carolina
United States	Penn State University	Hershey	Pennsylvania
United States	Clinical Trial Network	Houston	Texas
United States	University Physicians & Surgeons, Inc. dba Marshall Health	Huntington	West Virginia
United States	Interspond - Metrolina Neurological Associates	Indian Land	South Carolina
United States	Evergreen Health - Booth Gardner Parkinson's Care Center	Kirkland	Washington
United States	Interspond - Neurology Center of Las Vegas	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Neurology Associates Clinical Research	Lincoln	Nebraska
United States	Clinical Trials, Inc.	Little Rock	Arkansas
United States	Elias Research - Allied Biomedical Research Institute	Miami	Florida
United States	Elias Research - Floridian Research Institute	Miami	Florida
United States	Pharmax Research of South Florida	Miami	Florida
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Sentara Neuroscience Institute	Norfolk	Virginia
United States	Care Access Research, Norwich	Norwich	Connecticut
United States	Pacific Neuroscience Medical Group	Oxnard	California
United States	SC3 Research - Pasadena	Pasadena	California
United States	MEDSOL Clinical Research	Port Charlotte	Florida
United States	Parkinson's Disease Treatment Center of SWFL	Port Charlotte	Florida
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	Trial Connections - Care Access Research, Santa Clarita	Santa Clarita	California
United States	Intercoastal Medical Group	Sarasota	Florida
United States	Banner Sun Health Research Institute	Sun City	Arizona
United States	University of South Florida	Tampa	Florida
United States	University of Toledo Medical Center	Toledo	Ohio
United States	Evolution Research Group - Neuroscience Research Institution	Toms River	New Jersey
United States	Neuroscience Researc Institute of NJ	Toms River	New Jersey
United States	The Movement Disorder Clinic of Oklahoma	Tulsa	Oklahoma
United States	Wake Forest Baptist Medical Center	Wake Forest	North Carolina
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Palm Beach Neurology and Premier Research Institute	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Enterin Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Camilleri M, Subramanian T, Pagan F, Isaacson S, Gil R, Hauser RA, Feldman M, Goldstein M, Kumar R, Truong D, Chhabria N, Walter BL, Eskenazi J, Riesenberg R, Burdick D, Tse W, Molho E, Robottom B, Bhatia P, Kadimi S, Klos K, Shprecher D, Marquez-Mendoza — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Number of Participants Who Experience Treatment Related Adverse Events-Safety Endpoint	The number of treatment related adverse events as reported and assessed by NCI CTCAE v.4.3.	Through Study treatment up to 10 weeks
Primary	The Number of Participants Who Experience Dose Limiting Toxicity Adverse Events	The number of participants who experience dose limiting toxicity adverse events as reported and assessed by NCI CTCAE v.4.3.; Per protocol, dose limiting toxicity adverse events are vomiting, diarrhea, abdominal pain and dizziness.	Through Study treatment Dosing Period up to 10 weeks
Primary	Change in Baseline Weekly CSBM-Primary Efficacy Endpoint	Change from participant's weekly CSBM baseline rate during treatment fixed Dose period.; The fixed dose period begins on the first day or the subject's highest dose at which the subject did not experience a dose limiting toxicity (nausea, vomiting, diarrhea or dizziness) The fixed dose period will not be a specific time period for all subjects since each subject will start the fixed dose period based on their tolerability to ENT-01 dosing.	25 day treatment period, part of which is at a fixed dose.