Clinical trial NCT04483479: Orally Administered ENT-01 for Parkinson's Disease-Related Constipation Follow-on Safety "Roll-over" Study (Rollover)
Official title: A Multicenter, Non-Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Orally Administered ENT-01 in Improving Constipation and Neurologic Symptoms in Patients With Parkinson's Disease and Constipation Over a 14-week Period
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Parkinson Disease
Constipation
Lead sponsor: Enterin Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-23
Enrollment: 27
Sex: ALL
Minimum age (years): 30
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a Phase 2b, non-randomized, open-label study.
Primary purpose: TREATMENT

Brief summary: This study will be conducted as an open-label safety follow-on to a multi-center, double-blind, randomized study. All subjects who participated in the randomized study will be offered participation in this unblinded, single-arm, safety study. Approximately 50 subjects will be entered into the study and ENT-01 will be administered daily in escalating doses followed by a fixed dose for 12 weeks. Each subject will participate for approximately 20 weeks; dosing duration will be approximately 14 weeks.

Detailed description: The study will be conducted on an out-patient or in-patient basis with visits performed at the screening visit, at 6 and 12 weeks, and at the end of the 6th week of the wash-out period (end of study).

The dose escalation period will last up to 20 days, the fixed dose period will last 12 weeks, and the wash-out period will last 6 weeks.

Subjects will begin dosing at the same dose level they were stratified to in the ENT-01-030 randomized study (i.e., starting at either 3 tablets or 6 tablets,) and escalate up to a pro-kinetic dose or a maximum dose of 250mg.

Eligibility criteria: Inclusion Criteria:

1. All subjects who participated in the randomized study ENT-01-030 (KARMET Stage 2 Extension subjects) and who completed the dosing period.
2. Subjects aged 30-90 years at the time of screening for the ENT-01-030 study, both genders
3. Subjects must provide informed consent and be willing and able to comply with study procedures.
4. Subjects must be able to read, understand, and accurately record data into the diary to guarantee full participation in the study.
5. 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.
6. 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. Unable to withdraw proton pump inhibitors.
3. 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.
4. Diagnosis of secondary constipation beyond that of Parkinson's disease.
5. A compromised gastrointestinal system which includes:

   * Structural, metabolic, or functional GI diseases or disorders.
   * Acute GI illness within 2 weeks of the screening visit.
   * 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).
6. Neurological disorder other than Parkinson's disease that in the opinion of the investigator might interfere with the conduct of the study.
7. On treatment with intra-jejunal dopamine or carbidopa/levodopa (i.e. Duopa).
8. Subjects starting a new Parkinson's disease medication or modifying an existing medication within 2 weeks prior to enrollment.
9. Unable to maintain a stable diet regimen.
10. Subjects with a cognitive impairment that preclude them from understanding the informed consent.
11. Subjects placed under legal guardianship.
12. History of excessive alcohol use or substance abuse.
13. Any clinically significant abnormalities on screening laboratories or physical examination requiring further evaluation or treatment.
14. Females who are pregnant or breastfeeding.
15. Subject or caregiver unable to administer daily oral dosing of study drug.
16. Participation in a non-Enterin investigational drug trial within the month prior to dosing in the present study.
17. Any other reason, which in the opinion of the investigator would confound proper interpretation of the study.

Primary outcomes:
measure: Number of Participants With Treatment Related Adverse Events
timeFrame: Through study treatment and completion up to 14 weeks
measure: Number of Participants With Treatment Related Recurrent Vomiting
timeFrame: Through study treatment and completion up to 14 weeks
measure: Number of Participants With Treatment Related Recurrent Diarrhea
timeFrame: Through study treatment and completion up to 14 weeks
measure: Number of Participants With Treatment Related Dizziness
timeFrame: Through study treatment and completion up to 14 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: The Parkinson's and Movement Disorder Institute
state: California
city: Pasadena
country: United States
facility: SC3 Research - Pasadena
state: California
city: Englewood
country: United States
facility: Rocky Mountain Movement Disorders Center
state: Colorado
city: Washington
country: United States
facility: Georgetown Universtiy, Department of Neurology
state: District of Columbia
city: Atlantis
country: United States
facility: JEM Research Institute
state: Florida
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Port Charlotte
country: United States
facility: Parkinson's Disease Treatment Center of SWFL
state: Florida
city: Sarasota
country: United States
facility: Intercoastal Medical Group
state: Florida
city: Tampa
country: United States
facility: USF Health Byrd Parkinson's Disease Movement Disorders Center of Excellence
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute at Palm Beach Neurology
state: Florida
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Hershey
country: United States
facility: Penn State University
state: Pennsylvania
city: Kirkland
country: United States
facility: Evergreen Health - Booth Gardner Parkinson's Care Center
state: Washington
city: Huntington
country: United States
facility: University Physicians & Surgeons, Inc. dba Marshall Health
state: West Virginia
Study officials:
affiliation: Enterin Inc.
name: Michael Zasloff, MD, PhD
role: STUDY_CHAIR
affiliation: Enterin Inc.
name: Denise Barbut, MD, FRCP
role: STUDY_DIRECTOR
References: