Clinical trial NCT03938922: A Study to Evaluate ENT-01 for the Treatment of Parkinson's Disease Dementia
Official title: A Multicenter, Open Label Study to Evaluate Tolerability and Efficacy of Orally Administered ENT-01 for the Treatment of Parkinson's Disease Dementia.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Parkinson Disease
Dementia
Keywords: PDD
parkinson's disease-related dementia
Lead sponsor: Enterin Inc.
Sponsor class: INDUSTRY
First posted: 2019-05-06
Enrollment: 0
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
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cognition Improvement by Dementia Severity Rating Scale (DSRS) - Primary Outcome
timeFrame: 10 weeks
Secondary outcomes:
measure: Change from Baseline in Montreal Cognitive Assessment (MOCA) - Secondary Outcomes
timeFrame: 10 weeks
measure: Change from Baseline to the End of the Fixed Dose Period in Symptoms Adapted for Parkinson's Disease (SAPS-PD) - Secondary Outcomes
timeFrame: 10 weeks
measure: Change from Baseline to the End of the Fixed Dose Period in Neuropsychiatric Inventory (NPI) and Caregiver Distress (NPI-D) - Secondary Outcomes
timeFrame: 10 weeks
measure: Change from Baseline to the End of the Fixed Dose Period in Parkinson's Disease Questionnaire-39 (PDQ-39) - Secondary Outcomes
timeFrame: 10 weeks
Other outcomes:
measure: To compare the effect of ENT-01 on motor and non-motor symptoms of Parkinson's disease including Movement Disorder Society - Unified Parkinsons' Disease Rating Scale (MDS-UPDRS).
timeFrame: 10 weeks
measure: To compare the effect of ENT-01 on non-motor symptoms of Parkinson's disease for skin-temperature determined Circadian rhythm and weight.
timeFrame: 10 weeks
measure: To compare the effect of ENT-01 on non-motor symptoms of Parkinson's disease for weight.
timeFrame: 10 weeks
Locations:
city: Fresno
country: United States
facility: Neuro Pain Medical Center
state: California
city: Toms River
country: United States
facility: Evolution Research Group - Neuroscience Research Institution
state: New Jersey
city: Dayton
country: United States
facility: Elias Research - Neurology Diagnostics Research
state: Ohio
Study officials:
affiliation: Enterin Inc.
name: Michael Zasloff, MD, Ph.D
role: STUDY_CHAIR
affiliation: Enterin Inc.
name: Denise Barbut, MD, FRCP
role: STUDY_CHAIR
References: