Evaluation of Safety and Tolerability of ENT-01 for the Treatment of Parkinson's Disease Related Constipation

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
• If of child-bearing age: Must agree to using a hormonal (i.e., oral, implantable, or injectable) and either single- or double-barrier method of birth control throughout the study period. A vasectomized partner will be allowed as one in conjunction with another single-barrier method.
• If unable to have children: Must have this documented in the case report form (i.e., ubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since last menstrual period]). Post-menopausal status will be confirmed by follicle stimulating hormone in women less than 60 years of age.

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)
• Unable to maintain a stable diet regimen
• Patients with a cognitive impairment that preclude them from understanding the informed consent
• Patients placed under legal guardianship
• Acute GI illness within 48 hours of the baseline period
• History of major GI surgery (e.g. previous abdominal surgery, including cholecystectomy), except that patients with uncomplicated appendectomy are allowed
• ALT or AST > 1.5 X upper limit of normal (ULN) during screening
• Females who are pregnant or breastfeeding
• History of excessive alcohol use or substance abuse
• Patient or caregiver unable to administer daily oral dosing
• Participation in an investigational clinical study within the 6 months prior to dosing in the present study
• Any other reason, which in the opinion of the Investigator would confound proper interpretation of the study