A Study to Evaluate ENT-01 for the Treatment of Parkinson's Disease Dementia

A Multicenter, Open Label Study to Evaluate Tolerability and Efficacy of Orally Administered ENT-01 for the Treatment of Parkinson's Disease Dementia.

This study will be conducted as a multi-center, open label study in the US. There will be 40 patient to receive the active investigational product.

The study will be conducted on an out-patient basis. Each patient will have 5 visits to the clinic: a screening visit, a randomization visit, 1 followup visit, 1 end of treatment visit, and 1 end of study visit.

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.

Inclusion Criteria:

• Patients aged 30-90 years, both genders
• Patients or care-giver must provide informed consent and be willing and able to comply with study procedures.
• Patients 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.
• Patients must have dementia as defined by (1) decline in cognitive function and (2) functional impairment, which together in, in the opinion of the investigator, has resulted in a clinical diagnosis of dementia.
• MoCA < 24 in support of a dementia diagnosis
• Have a reliable and actively involved caregiver who must be able to communicate in English and be willing to comply with protocol requirements.
• If on anti-parkinsonian agents, participants must be on stable dosage for at least 4 weeks prior to baseline.
• If on medications enhancing cognition (rivastigmine, galantamine, donepezil, memantine), participants must be on stable dosage for at least 8 weeks prior to baseline.
• If on antidepressant medications, participants must be on stable dosage for at least 4 weeks prior to baseline.
• If on clozapine, pimavanserin or quetiapine to address drug-induced or disease-related psychosis, participants must be on stable dosage for 4 weeks prior to baseline.
• Female patients of childbearing potential 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.
• Female patients unable to bear children must have this documented in the case report form (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:

• Patient or caregiver unable or unwilling to provide informed consent or to comply with study procedures.
• Unable to withdraw proton pump inhibitors at the end of run-in period.
• Unable to withdraw from anti-cholinergics at the beginning of the run-in period
• Any clinically significant abnormalities on screening laboratories or physical examination requiring further evaluation or treatment.
• Neurological disorder other than Parkinson's disease that in the opinion of the investigator might interfere with the conduct of the study
• Females who are pregnant or breastfeeding
• History of excessive alcohol use or substance abuse
• Psychotic disorder was present before the diagnosis of Parkinson's disease
• Patient or caregiver unable to administer daily oral dosing of study drug
• Caregiver unwilling or unable to unable to complete stool diary, dispense study medication and accompany the patient to all visits
• Participation in an investigational drug trial within the month prior to dosing in the present study.
• A compromised gastrointestinal system which includes: Structural, metabolic, or functional GI diseases or disorders; History of major GI surgery within 30 days (a history of cholecystectomy, polypectomy, hernia repair, appendicectomy, gastric surgery for peptic ulcer and gastric banding for obesity are not exclusionary as long as they were performed more than 30 days before the screening visit. Partial or complete colectomy is exclusionary).
• Review of Screening period diaries indicates either of the following: Fewer than 11 days of diary completion; More than 5 complete spontaneous bowel movements per week based upon the average Complete Spontaneous Bowel Movement (CSBM) rate reported during the Screening Period.
• Any other reason, which in the opinion of the investigator would confound proper interpretation of the study.