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

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ClinicalTrials.gov Identifier: NCT03781791
Recruitment Status : Recruiting
First Posted : December 20, 2018
Last Update Posted : December 25, 2018
Sponsor:
Information provided by (Responsible Party):
Enterin Inc.

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.

Condition or disease Intervention/treatment Phase
Constipation Parkinson Disease 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 10 patients to consent to the pk study will have additional blood samples taken at randomization and at 2 follow up visits. The first 10 patients to consent to the stool microbiome study will provide stool samples at randomization and at 2 follow up visits.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 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 : December 10, 2018
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine


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 Name: 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.




Primary Outcome Measures :
  1. Incidence of Treatment Related Adverse Events-Safety Endpoint [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Through Study Treatment Dosing Period up to 10 weeks ]
    Change from participant's weekly CSBM baseline rate during treatment fixed Dose period.

  4. Change in baseline stool Microbiome - Exploratory Outcome [ Time Frame: 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


Secondary Outcome Measures :
  1. Change in participant constipation severity from baseline-Secondary Efficacy Endpoints [ Time Frame: 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.



Information from the National Library of Medicine

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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. Subjects aged 30-86 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.

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): NCT03781791


Contacts
Contact: Denise Barbut, MD, FRCP (215) 634-9243 d.barbut@enterininc.com

Locations
United States, California
Neuro Pain Medical Center Recruiting
Fresno, California, United States, 93710
Contact: Perminder Bhatia, MD    559-437-9700    BHATIA@neuropain.com   
Principal Investigator: Perminder Bhatia, MD         
Sub-Investigator: David Baker, PAC         
United States, Connecticut
Associated Neurologist of Southern CT Recruiting
Fairfield, Connecticut, United States, 06824
Contact: Irina Gamerman    203-333-1151 ext 2    igamerman@anscneuro.com   
Principal Investigator: Srinath Kadimi, MD         
United States, Florida
Elias Research - Jem Research Institute Recruiting
Atlantis, Florida, United States, 33462
Contact: Melissa Daggerhart    561-968-2933    mdaggerhart@jemri.net   
Principal Investigator: Mark Goldstein, MD         
Sub-Investigator: Eric D. Kramer, MD         
Sub-Investigator: Cassandra I. Mateo, MD         
Sub-Investigator: Elizabeth R. Sheldon, ARNP         
Sub-Investigator: Mara Bailey, Psy. D.         
Sub-Investigator: Anna L. Curtis         
University of South Florida Active, not recruiting
Tampa, Florida, United States, 33603
United States, Indiana
BTC Network - Community Clinical Research Center Recruiting
Anderson, Indiana, United States, 46011
Contact: Lesia McBride    765-298-2040    lmcbride@ecommunity.com   
Principal Investigator: Larry Blankenship, MD         
United States, Louisiana
Interspond - The Neuromedical Clinic of Central Louisiana Recruiting
Alexandria, Louisiana, United States, 71301
Contact: Julie Clement, RDN, LDN    608-848-8900    ghidalgo@interspond.com   
Principal Investigator: Gonzalo Hidalgo, MD         
Sub-Investigator: Ariel Orlando Antezana-Antezana, MD         
Sub-Investigator: Julie Clement, RDN, LDN         
United States, Maryland
Parkinson's and Movement Disorders Center of Maryland Recruiting
Elkridge, Maryland, United States, 21075
Contact: Stephen Grill, MD    443-755-0030    sgrill@pdmdcenter.com   
Principal Investigator: Stephen Grill, MD         
Sub-Investigator: Molly Del Santo, MD         
Sub-Investigator: Steven Geller, MD         
United States, Nebraska
Neurology Associates Clinical Research Recruiting
Lincoln, Nebraska, United States, 68506
Contact: Greg Rugh    402-486-3430    greg@somnos.com   
Principal Investigator: Gary Pattee, MD         
Sub-Investigator: James A. Bobenhouse, MD         
Sub-Investigator: Ashley D. Calhoun, LPN         
Sub-Investigator: Desirae R. Eschiti, LPN         
United States, New Jersey
Evolution Research Group - Neuroscience Research Institution Active, not recruiting
Toms River, New Jersey, United States, 08755
United States, Ohio
Elias Research - Neurology Diagnostics Research Recruiting
Dayton, Ohio, United States, 45459
Contact: Robin McKeen    208-346-8900    Joel.Vandersluis@eliasresearch.com   
Principal Investigator: Joel Vandersluis, MD         
Sub-Investigator: Leah Lang         
Sub-Investigator: Abdelfatah Abou Issa         
United States, Oklahoma
The Movement Disorder Clinic of Oklahoma Recruiting
Tulsa, Oklahoma, United States, 74136
Contact: Melissa Benson    918-392-4530    melissa.benson@mdcok.com   
Principal Investigator: Kevin Klos, MD         
United States, Pennsylvania
Penn State University Not yet recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Bryan Mullen    717-425-0419    bmullen1@pennstatehealth.psu.edu   
Principal Investigator: Thyagarajan Subramanian, MD         
United States, Virginia
Sentara Neuroscience Institute Recruiting
Norfolk, Virginia, United States, 23456
Contact: Lisa H Richardson    757-507-0642    lhrichar@sentara.com   
Principal Investigator: Karen M Thomas, DO         
Sponsors and Collaborators
Enterin Inc.
Investigators
Study Chair: Michael Zasloff, MD PhD Enterin Inc.
Study Director: Denise Barbut, MD, FRCP Enterin Inc.

Responsible Party: Enterin Inc.
ClinicalTrials.gov Identifier: NCT03781791     History of Changes
Other Study ID Numbers: ENT-01-030
First Posted: December 20, 2018    Key Record Dates
Last Update Posted: December 25, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
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
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