test of 6 cognitive or functional domains, including memory, orientation, judgment, community affairs, home hobbies, and personal care are scored by certified raters after interviewing both participants and their informants. Higher score is indicative of more severe disease. The minimum score is 0 and the maximum score is 18. The CDR-SB is a co-primary outcome with ADAS-Cog12

The ADAS-Cog was developed to assess the level of cognitive dysfunction in Alzheimer's disease. It is also used in studies of interventions in people with mild cognitive impairment. It is also used for assessing the efficacy of antidementia treatments. The test is administered and scored by a certified rater to assess the cognitive domains of memory, language, orientation and praxis. A higher score is indicative of more severe disease, with 0 (no cognitive deficit) being the lowest score possible and 80 being the highest score and associated with severe cognitive impairment. ADAS-Cog12 is a co-primary outcome with CDR-SB.

Primary endpoints assessed changes from baseline in neurophysiological health and oxidative stress using advanced neuroimaging analyses. Analysis methods utilized blinded expert evaluation between baseline and completion scans.

Objective computerized neurocognitive testing assessing attention, sustained attention, verbal memory, verbal learning, psychomotor function and processing speed. A composite cognitive score is calculated as the mean of standardized (z-score-transformed) performance scores across the tasks. Higher composite scores indicate better cognitive performance. \*This study is designed as a signal-seeking proof-of-concept Phase 2 study. The primary outcome is intended for estimation and hypothesis generation rather than formal hypothesis testing. No single endpoint is designated as definitive for study success

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is comprised of 4 parts: This study will use MDS-UPDRS Parts I, II, and III. The primary efficacy endpoint is change in the modified MDS-UPDRS Part III score. Scores (0-4: Normal to severe impact) are derived from clinician and subject input to allow the assessment of symptomatic worsening, stability, or improvement.

Unified Parkinson's disease rating scale Part III total score is the cumulative score of a 33 question assessment of disease impact on patient's ability to move, with each part scored on a scale of 0-4, with 0 being no effect of disease and 4 being severe disease. a total score of 0 indicates no disease and a total score of 132 indicates the most severe disease

The total sum of time in which a patient self categorizes themselves as in the "off" state determined by diary entries. 0 hours is the minimum/best score, which indicates continuous L-dopa-like activity for the 24 hour period. 24 hours is the worst score and indicates that there was no L-dopa-like benefit at any time during the 24 hour period.

An average score will be calculated from assessments of the Unified Parkinson's disease rating scale Part III total score, which is the cumulative score of a 33 question assessment of disease impact on patient's ability to move, with each question scored on a scale of 0-4, with 0 being no effect of disease and 4 being severe disease. a total score of 0 indicates no disease and a total score of 132 indicates the most severe disease. Scores will be collected several times during the eight hours following L-dopa and/or NE3107 administration.

the cumulative score of a 13 question assessment of disease impact on patient's cognitive impairment, with each question scored on a scale of 0-4, with 0 being no effect of disease and 4 being severe disease. a total score of 0 indicates no disease and a total score of 42 indicates the most severe disease. This test asks about the impact of disease on cognition, but does not directly measure cognitive capability.

the cumulative score of a 13 question assessment of disease impact on patient's Motor Aspects of Experiences of Daily Living, with each question scored on a scale of 0-4, with 0 being no effect of disease and 4 being a severe effect. a total score of 0 indicates no disease and a total score of 42 indicates the most severe disease.

The total sum of time in which a patient self categorizes themselves as in the "on" state, with or without dyskinesia determined by diary entries. 0 hours is the minimum/worst score, which indicates no L-dopa-like activity for the 24 hour period. 24 hours is the best score and indicates that there was no L-dopa-like benefit at any time during the 24 hour period.

AIMS is a 12-item clinician-rated scale to assess severity of dyskinesias (orofacial movements and extremity and truncal movements) in patients taking L-dopa. Questions assess the overall severity, incapacitation, and the patient's level of awareness of the movements, and distress associated with them. Questions are scored from 0 (no symptom) to 4 (severe). the minimum total score of 0 indicates no dyskinesia and the maximum total score of 48 indicates severe dyskinesia.

Length of time from L-dopa administration to beginning of L-dopa activity producing "on-state". Patient self assessment of the time L-dopa-like activity begins after L-dopa administration. A decrease in the time to onset may shorten the time in the off-state and be considered a patient benefit. An increase in time to onset may lengthen time in the off-state and be considered a general worsening of response to treatment.

The Non-Motor Symptoms Scale (NMSS) is a 30-item rater-based scale to assess a wide range of non-motor symptoms in patients with Parkinson's disease (PD). The NMSS measures the severity and frequency of non-motor symptoms across nine dimensions. The scale can be used for patients at all stages of PD. For each question, scores of severity (0 to 3, with 0 being none and 3 being major source of distress) and frequency (1 to 4, 1= rarely and 4 = very frequent) are recorded and the product of the two calculated. The sum of the products yields the overall score. The minimum total score of 0 indicates no non-motor symptoms and the maximum score of 360 indicates severe disease.

the plasma concentration vs time curve for L-dopa will be calculated from the L-dopa concentration in plasma samples collected prior to dosing and at 0.5, 1, 2, 3, 4, and 8 hours after L-dopa administration on days on which NE3107 is not administered (Day 1) and three days on which NE3107 is co-administered (Day 2, 3, and 14). Changes in L-dopa area under the curve could be associated with changes in activity against motor symptoms of disease.

the maximum plasma concentration for L-dopa will be determined in plasma samples collected prior to dosing and at 0.5, 1, 2, 3, 4, and 8 hours after L-dopa administration on days on which NE3107 is not administered (Day 1) and three days on which NE3107 is co-administered (Day 2, 3, and 14). Changes in L-dopa Cmax could be associated with changes in activity against motor symptoms of disease.

the plasma concentration vs time curve for NE3107 will be calculated from the NE3107 concentration in plasma samples collected prior to dosing and at 0.5, 1, 2, 3, 4, and 8 hours

the maximum plasma concentration for NE3107 will be determined in plasma samples collected prior to dosing and at 0.5, 1, 2, 3, 4, and 8 hours after NE3107 administration