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

NCT03781791 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ENT-01-030
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 51

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.

Conditions

Constipation; Parkinson Disease

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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.

Study Arms (2)

Active Treatment

EXPERIMENTAL

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

Drug: Active Investigational Treatment ENT-01

Placebo Treatment

PLACEBO COMPARATOR

Placebo tablet will be taken once daily by mouth.

Drug: Placebo Treatment

Interventions

Active Investigational Treatment ENT-01 DRUG

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

Also known as: ENT-01

Active Treatment

Placebo Treatment DRUG

Placebo will be administered in tablet form, once daily.

Placebo Treatment

Eligibility Criteria

• Age: 30 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects aged 30-90 years, both genders
• Subjects must provide written informed consent and be willing and able to comply with study procedures.
• 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.
• There are insufficient criteria for Irritable Bowel Syndrome (IBS)
• 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.
• Body mass index (BMI) of 18-40 kg/m2
• Subjects must fulfill Rome IV criteria for functional constipation which includes 2 or more of the following:
• Straining during at least 25% of defecations
• Lumpy or hard stools in at least 25% of defecations
• Sensation of incomplete evacuation for at least 25% of defecations
• Sensation of anorectal obstruction/blockage for at least 25% of defecations
• Manual maneuvers to facilitate at least 25% of defecations (e.g., digital evacuation, support of the pelvic floor)
• Self-report of fewer than 3 complete spontaneous bowel movements per week
• Loose stools are rarely present without the use of laxatives
• Subjects must be able to read, understand, and accurately record data into the diary to guarantee full participation in the study.

You may not qualify if:

• Unable or unwilling to provide informed consent or to comply with study procedures.
• Diagnosis of secondary constipation beyond that of Parkinson's Disease
• 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
• A compromised gastrointestinal system which includes:
• Structural, metabolic, or functional GI diseases or disorders
• Acute GI illness within 2 weeks of the screening visit
• 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.
• Unable or unwilling to withdraw from proton pump inhibitors and antacids at the end of the screening period.
• Unable or unwilling to withdraw from pimavanserin during the study.
• Any clinically significant abnormalities on screening laboratories or physical examination requiring further evaluation or treatment.
• Neurological disorder other than Parkinson's Disease that in the opinion of the investigator might interfere with the conduct of the study.
• On treatment with intra-jejunal dopamine or carbidopa/levodopa (i.e. Duopa).
• Subjects starting a new Parkinson's Disease medication or modifying an existing medication within 2 weeks prior to enrollment.
• Unable to maintain a stable diet regimen.
• Subjects with a cognitive impairment that preclude them from understanding the informed consent.

Sponsors & Collaborators

• Enterin Inc.: lead

Study Sites (51)

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

Clinical Trials, Inc.

Little Rock, Arkansas, 72205, United States

Location

The Parkinson's and Movement Disorder Institute

Fountain Valley, California, 92708, United States

Location

Neuro Pain Medical Center

Fresno, California, 93710, United States

Location

Pacific Neuroscience Medical Group

Oxnard, California, 93030, United States

Location

SC3 Research - Pasadena

Pasadena, California, 91105, United States

Location

Trial Connections - Care Access Research, Santa Clarita

Santa Clarita, California, 91321, United States

Location

Rocky Mountain Movement Disorders Center

Englewood, Colorado, 80113, United States

Location

Associated Neurologist of Southern CT

Fairfield, Connecticut, 06824, United States

Location

Care Access Research, Norwich

Norwich, Connecticut, 06360, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

JEM Research Institute

Atlantis, Florida, 33462, United States

Location

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

Elias Research - Floridian Research Institute

Miami, Florida, 33145, United States

Location

Elias Research - Allied Biomedical Research Institute

Miami, Florida, 33155, United States

Location

Pharmax Research of South Florida

Miami, Florida, 33175, United States

Location

MEDSOL Clinical Research

Port Charlotte, Florida, 33952, United States

Location

Parkinson's Disease Treatment Center of SWFL

Port Charlotte, Florida, 33980, United States

Location

Intercoastal Medical Group

Sarasota, Florida, 34239, United States

Location

University of South Florida

Tampa, Florida, 33603, United States

Location

Palm Beach Neurology and Premier Research Institute

West Palm Beach, Florida, 33407, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

BTC Network - Community Clinical Research Center

Anderson, Indiana, 46011, United States

Location

Interspond - The Neuromedical Clinic of Central Louisiana

Alexandria, Louisiana, 71301, United States

Location

The NeuroMedical Center, P.C.

Baton Rouge, Louisiana, 70810, United States

Location

Parkinson's and Movement Disorders Center of Maryland

Elkridge, Maryland, 21075, United States

Location

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, 48322, United States

Location

Neurology Associates Clinical Research

Lincoln, Nebraska, 68506, United States

Location

Interspond - Neurology Center of Las Vegas

Las Vegas, Nevada, 89128, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 13756, United States

Location

Evolution Research Group - Neuroscience Research Institution

Toms River, New Jersey, 08755, United States

Location

Neuroscience Researc Institute of NJ

Toms River, New Jersey, 08755, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Raleigh Neurology Associates

Raleigh, North Carolina, 27607, United States

Location

Wake Forest Baptist Medical Center

Wake Forest, North Carolina, 27157, United States

Location

Dayton Center for Neurological Disorders

Centerville, Ohio, 45459, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44095, United States

Location

Elias Research - Neurology Diagnostics Research

Dayton, Ohio, 45459, United States

Location

University of Toledo Medical Center

Toledo, Ohio, 43614, United States

Location

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, 74136, United States

Location

Penn State University

Hershey, Pennsylvania, 17033, United States

Location

Interspond - Premier Neurology

Greer, South Carolina, 29650, United States

Location

Interspond - Metrolina Neurological Associates

Old Point Station, South Carolina, 29707, United States

Location

North Texas Movement Disorders Institute

Bedford, Texas, 76021, United States

Location

BTC Network - Neurological Associates of North Texas

Dallas, Texas, 75218, United States

Location

Clinical Trial Network

Houston, Texas, 77074, United States

Location

Sentara Neuroscience Institute

Norfolk, Virginia, 23456, United States

Location

Evergreen Health - Booth Gardner Parkinson's Care Center

Kirkland, Washington, 98034, United States

Location

University Physicians & Surgeons, Inc. dba Marshall Health

Huntington, West Virginia, 25701, United States

Location

Related 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 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.

  PMID: 36343348 RESULT

MeSH Terms

Conditions

Constipation; Parkinson Disease

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Richard Larson, MD Chief Medical Officer
• Organization: Enterin

r.larson@enterininc.com

505-469-2670

Study Officials

• Michael Zasloff, MD PhD

  Enterin Inc.

  STUDY CHAIR

• Denise Barbut, MD, FRCP

  Enterin Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: December 20, 2018
• Study Start: December 10, 2018
• Primary Completion: December 14, 2021
• Study Completion: December 14, 2021
• Last Updated: February 20, 2024
• Results First Posted: December 4, 2023

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (51)