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

Sponsor
Enterin Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03781791
Collaborator
(none)
144
Enrollment
51
Locations
2
Arms
36.1
Actual Duration (Months)
2.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Active Investigational Treatment ENT-01
  • Drug: Placebo Treatment
 Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
144 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Dec 10, 2018
Actual Primary Completion Date :
Dec 14, 2021
Actual Study Completion Date :
Dec 14, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Active Treatment

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

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

    		•
    Placebo Comparator: Placebo Treatment

    Placebo tablet will be taken once daily by mouth.

    Drug: Placebo Treatment
    Placebo will be administered in tablet form, once daily.

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of Treatment Related Adverse Events-Safety Endpoint [Through Study treatment up to 10 weeks]

      The number of treatment related adverse events as reported and assessed by NCI CTCAE v.4.3.

    2. Incidence of Treatment Related Adverse Event-Tolerability Endpoints [Through Study treatment Dosing Period up to 10 weeks]

      The number of treatment related adverse events as reported and assessed by NCI CTCAE v.4.3.

    3. Change in baseline weekly CSBM-Primary Efficacy Endpoint [Through Study Treatment Dosing Period up to 10 weeks]

      Change from participant's weekly CSBM baseline rate during treatment fixed Dose period.

    Secondary Outcome Measures

    1. Change in participant constipation severity from baseline-Secondary Efficacy Endpoints [Through Study Treatment Dosing Period up to 10 weeks]

      Participant reported change from baseline as assessed according to Bristol Stool rating scale (0-5) of increasing severity of ease of bowel evacuation.

    Other Outcome Measures

    1. Change in baseline stool Microbiome - Exploratory Outcome [Through Study Treatment Dosing Period and Completion up to 24 weeks]

      Collection of participant baseline intestinal microbiome condition as observed in stool to on treatment related effect of ENT-01 on stool microbiome

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    30 Years to 90 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

    8. Straining during at least 25% of defecations

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

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

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

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

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

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

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

    16. 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.

    17. 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:

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

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

    7. 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)

    8. 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.

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

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

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

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

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

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

    15. Unable to maintain a stable diet regimen.

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

    17. Subjects placed under legal guardianship.

    18. Females who are pregnant or breastfeeding.

    19. History of excessive alcohol use or substance abuse.

    20. Participation in an investigational drug trial within the month 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Banner Sun Health Research Institute Sun City Arizona United States 85351
    2 Clinical Trials, Inc. Little Rock Arkansas United States 72205
    3 The Parkinson's and Movement Disorder Institute Fountain Valley California United States 92708
    4 Neuro Pain Medical Center Fresno California United States 93710
    5 Pacific Neuroscience Medical Group Oxnard California United States 93030
    6 SC3 Research - Pasadena Pasadena California United States 91105
    7 Trial Connections - Care Access Research, Santa Clarita Santa Clarita California United States 91321
    8 Rocky Mountain Movement Disorders Center Englewood Colorado United States 80113
    9 Associated Neurologist of Southern CT Fairfield Connecticut United States 06824
    10 Care Access Research, Norwich Norwich Connecticut United States 06360
    11 Georgetown University Hospital Washington District of Columbia United States 20007
    12 JEM Research Institute Atlantis Florida United States 33462
    13 Parkinson's Disease and Movement Disorders Center of Boca Raton Boca Raton Florida United States 33486
    14 Elias Research - Floridian Research Institute Miami Florida United States 33145
    15 Elias Research - Allied Biomedical Research Institute Miami Florida United States 33155
    16 Pharmax Research of South Florida Miami Florida United States 33175
    17 MEDSOL Clinical Research Port Charlotte Florida United States 33952
    18 Parkinson's Disease Treatment Center of SWFL Port Charlotte Florida United States 33980
    19 Intercoastal Medical Group Sarasota Florida United States 34239
    20 University of South Florida Tampa Florida United States 33603
    21 Palm Beach Neurology and Premier Research Institute West Palm Beach Florida United States 33407
    22 Atlanta Center for Medical Research Atlanta Georgia United States 30331
    23 BTC Network - Community Clinical Research Center Anderson Indiana United States 46011
    24 Interspond - The Neuromedical Clinic of Central Louisiana Alexandria Louisiana United States 71301
    25 The NeuroMedical Center, P.C. Baton Rouge Louisiana United States 70810
    26 Parkinson's and Movement Disorders Center of Maryland Elkridge Maryland United States 21075
    27 Henry Ford West Bloomfield Hospital West Bloomfield Michigan United States 48322
    28 Neurology Associates Clinical Research Lincoln Nebraska United States 68506
    29 Interspond - Neurology Center of Las Vegas Las Vegas Nevada United States 89128
    30 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 13756
    31 Evolution Research Group - Neuroscience Research Institution Toms River New Jersey United States 08755
    32 Neuroscience Researc Institute of NJ Toms River New Jersey United States 08755
    33 Albany Medical College Albany New York United States 12208
    34 Icahn School of Medicine at Mount Sinai New York New York United States 10029
    35 Raleigh Neurology Associates Raleigh North Carolina United States 27607
    36 Wake Forest Baptist Medical Center Wake Forest North Carolina United States 27157
    37 Dayton Center for Neurological Disorders Centerville Ohio United States 45459
    38 University of Cincinnati Cincinnati Ohio United States 45219
    39 Cleveland Clinic Cleveland Ohio United States 44095
    40 Elias Research - Neurology Diagnostics Research Dayton Ohio United States 45459
    41 University of Toledo Medical Center Toledo Ohio United States 43614
    42 The Movement Disorder Clinic of Oklahoma Tulsa Oklahoma United States 74136
    43 Penn State University Hershey Pennsylvania United States 17033
    44 Interspond - Premier Neurology Greer South Carolina United States 29650
    45 Interspond - Metrolina Neurological Associates Indian Land South Carolina United States 29707
    46 North Texas Movement Disorders Institute Bedford Texas United States 76021
    47 BTC Network - Neurological Associates of North Texas Dallas Texas United States 75218
    48 Clinical Trial Network Houston Texas United States 77074
    49 Sentara Neuroscience Institute Norfolk Virginia United States 23456
    50 Evergreen Health - Booth Gardner Parkinson's Care Center Kirkland Washington United States 98034
    51 University Physicians & Surgeons, Inc. dba Marshall Health Huntington West Virginia United States 25701

    Sponsors and Collaborators

    • Enterin Inc.

    Investigators

    • Study Chair: Michael Zasloff, MD PhD, Enterin Inc.
    • Study Director: Denise Barbut, MD, FRCP, Enterin Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Enterin Inc.
    ClinicalTrials.gov Identifier:
    NCT03781791
    Other Study ID Numbers:
    • ENT-01-030
    First Posted:
    Dec 20, 2018
    Last Update Posted:
    Mar 22, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Parkinson Disease
    Constipation

    Study Results

    No Results Posted as of Mar 22, 2022