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

NCT ID: NCT03781791

Last Updated: 2024-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-10
• Study Completion Date: 2021-12-14

Brief 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.

Detailed 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.

Conditions

Constipation; Parkinson Disease

Study Design

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

Study Groups

Active Treatment

ENT-01 tablet will be taken once daily by mouth.

Group Type: EXPERIMENTAL

Active Investigational Treatment ENT-01

Intervention Type: DRUG

ENT-01 will be administered in tablet form, once daily.

Placebo Treatment

Placebo tablet will be taken once daily by mouth.

Group Type: PLACEBO_COMPARATOR

Placebo Treatment

Intervention Type: DRUG

Placebo will be administered in tablet form, once daily.

Interventions

Active Investigational Treatment ENT-01

ENT-01 will be administered in tablet form, once daily.

Intervention Type: DRUG

Placebo Treatment

Placebo will be administered in tablet form, once daily.

Intervention Type: DRUG

Other Intervention Names

ENT-01

Eligibility Criteria

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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Enterin Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Zasloff, MD PhD

Role: STUDY_CHAIR

Enterin Inc.

Denise Barbut, MD, FRCP

Role: STUDY_DIRECTOR

Enterin Inc.

Locations

Banner Sun Health Research Institute

Sun City, Arizona, United States

Clinical Trials, Inc.

Little Rock, Arkansas, United States

The Parkinson's and Movement Disorder Institute

Fountain Valley, California, United States

Neuro Pain Medical Center

Fresno, California, United States

Pacific Neuroscience Medical Group

Oxnard, California, United States

SC3 Research - Pasadena

Pasadena, California, United States

Trial Connections - Care Access Research, Santa Clarita

Santa Clarita, California, United States

Rocky Mountain Movement Disorders Center

Englewood, Colorado, United States

Associated Neurologist of Southern CT

Fairfield, Connecticut, United States

Care Access Research, Norwich

Norwich, Connecticut, United States

Georgetown University Hospital

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

JEM Research Institute

Atlantis, Florida, United States

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, United States

Elias Research - Floridian Research Institute

Miami, Florida, United States

Elias Research - Allied Biomedical Research Institute

Miami, Florida, United States

Pharmax Research of South Florida

Miami, Florida, United States

MEDSOL Clinical Research

Port Charlotte, Florida, United States

Parkinson's Disease Treatment Center of SWFL

Port Charlotte, Florida, United States

Intercoastal Medical Group

Sarasota, Florida, United States

University of South Florida

Tampa, Florida, United States

Palm Beach Neurology and Premier Research Institute

West Palm Beach, Florida, United States

Atlanta Center for Medical Research

Atlanta, Georgia, United States

BTC Network - Community Clinical Research Center

Anderson, Indiana, United States

Interspond - The Neuromedical Clinic of Central Louisiana

Alexandria, Louisiana, United States

The NeuroMedical Center, P.C.

Baton Rouge, Louisiana, United States

Parkinson's and Movement Disorders Center of Maryland

Elkridge, Maryland, United States

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, United States

Neurology Associates Clinical Research

Lincoln, Nebraska, United States

Interspond - Neurology Center of Las Vegas

Las Vegas, Nevada, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 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

Albany Medical College

Albany, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Raleigh Neurology Associates

Raleigh, North Carolina, United States

Wake Forest Baptist Medical Center

Wake Forest, North Carolina, United States

Dayton Center for Neurological Disorders

Centerville, Ohio, United States

University of Cincinnati

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Elias Research - Neurology Diagnostics Research

Dayton, Ohio, United States

University of Toledo Medical Center

Toledo, Ohio, United States

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, United States

Penn State University

Hershey, Pennsylvania, United States

Interspond - Premier Neurology

Greer, South Carolina, United States

Interspond - Metrolina Neurological Associates

Old Point Station, South Carolina, United States

North Texas Movement Disorders Institute

Bedford, Texas, United States

BTC Network - Neurological Associates of North Texas

Dallas, Texas, United States

Clinical Trial Network

Houston, Texas, United States

Sentara Neuroscience Institute

Norfolk, Virginia, United States

Evergreen Health - Booth Gardner Parkinson's Care Center

Kirkland, Washington, United States

University Physicians & Surgeons, Inc. dba Marshall Health

Huntington, West Virginia, United States

Countries

United States

References

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 O, Hidalgo G, Grill S, Li G, Mandell H, Hughes M, Stephenson S, Vandersluis J, Pfeffer M, Duker A, Shivkumar V, Kinney W, MacDougall J, Zasloff M, Barbut D. Oral ENT-01 Targets Enteric Neurons to Treat Constipation in Parkinson Disease : A Randomized Controlled Trial. Ann Intern Med. 2022 Dec;175(12):1666-1674. doi: 10.7326/M22-1438. Epub 2022 Nov 8.

Reference Type: RESULT

PMID: 36343348 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ENT-01-030

Identifier Type: -

Identifier Source: org_study_id