A Multi-Center, Single-Dose, Multiple-Dose, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered ENT-01 for the Treatment of Parkinson's Disease Related Constipation
Overview
- Phase
- Phase 1
- Intervention
- ENT-01
- Conditions
- Parkinson's Disease
- Sponsor
- Enterin Inc.
- Enrollment
- 50
- Locations
- 15
- Primary Endpoint
- Number of Participants With Treatment-related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events.
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a Phase 1/2a study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of an orally-administered medication to relieve symptoms of constipation associated with Parkinson's Disease. Ten patients will be enrolled in Phase 1, and will be studied over an 8-12 week period. Forty patients will be enrolled in Phase 2, and will be studied over an 8-10 week period. All subjects will receive the study drug during one of the observational periods of the study.
Detailed Description
Phase 1 will enroll 10 patients to assess the safety, tolerability, and pharmacokinetics of single escalating doses over a 30-60 day period. The dose-escalation period will be preceded by a 2-week run in period and followed by a 2-week wash-out period. Phase 2 follow the safe completion of Phase 1. It will enroll 40 patients and is composed of 4 periods of study: 1) a 2-week run-in period, 2) a 3-5 week escalating dose period to identify a prokinetic dose in the initial set of 10 patients, 3) a 1-week period of randomized dosing (placebo versus the previously identified pro-kinetic dose), and 4) a 2-week wash-out period. Pharmacodynamics will be assessed along with safety and tolerability. Relative outcomes will be compared within each patient and across groups for the randomized dosing period. Frequency of bowel movements and other non-motor symptoms of Parkinson's Disease will be collected over the course of both phases.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Parkinson's disease diagnosis confirmed by a neurologist specializing in movement disorders
- •Insufficient criteria for a diagnosis of Irritable Bowel Syndrome
- •Constipation for over 6 months, unresponsive to Milk of Magnesia, and requiring at least weekly treatment using an oral laxative, stool softener, bulking agent, and/or a suppository, and dissatisfaction with current treatment.
- •Body Mass Index is 18-40 kg/m2
- •At least 2 of the Rome IV functional constipation criteria are met
- •Loose stools are rarely present without the use of laxatives
- •Patient is willing and able to sign informed consent and comply with all study procedures
- •Patients must be able to read, understand, and accurately record data into the diary to guarantee full participation in the study
- •Females only:
- •Must have negative serum or urine pregnancy tests and must not be lactating
Exclusion Criteria
- •Unable or unwilling to provide informed consent or to comply with study procedures
- •Diagnosis of secondary constipation beyond that of PD
- •Structural or metabolic diseases that affect the GI system
- •Functional GI disorder
- •Unable or unwilling to withdraw from taking the following medications 2 weeks prior to the dose-escalation period and throughout the study: Laxatives, opiates, sedatives, hypnotics, anti-histamines, protein pump inhibitors or any medications which may cause constipation
- •History of recent major surgery (within 60 days of screening)
- •Any clinically significant abnormalities on screening laboratories or physical examination as determined by the Investigator
- •Neurological disorder other than PD
- •On treatment with intra-jejunal dopamine
- •Treatment with COMT inhibitors for fewer than 4 weeks (entacapone, tolcapone, Stalevo)
Arms & Interventions
ENT-01
ENT-01 at a to-be-determined dose taken by mouth every day upon awakening.
Intervention: ENT-01
Placebo Comparator
Placebo to be taken by mouth every day upon awakening
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants With Treatment-related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events.
Time Frame: Through study completion, up to 11 weeks
Specific treatment related events of recurrent vomiting, recurrent diarrhea, abdominal pain, and hypotension will be assessed with respect to grade and frequency of occurrence.
Secondary Outcomes
- Frequency of Bowel Movements(Through study completion, up to 11 weeks)