NYX-458 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson's Disease or Lewy Body Dementia (Cognition, Memory, Attention, Thinking)

Study Overview
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Brief Summary
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A Study to Evaluate NYX-458 in Subjects With Mild Cognitive Impairment or Mild Dementia Associated With Parkinson's Disease or Prodromal or Manifest Lewy Body Dementia

Detailed Description
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The study will be a 16 to 18-week study, including a 2 to 4-week screening period, followed by a 12-week double-blind, randomized, placebo-controlled treatment Period, and a 2-week follow-up period. Subjects eligible for the study will be randomized to receive either NYX-458 or placebo.

Official Title
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A Study to Evaluate NYX-458 in Subjects With Mild Cognitive Impairment or Mild Dementia Associated With Parkinson's Disease or Prodromal or Manifest Lewy Body Dementia

Conditions
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Mild Cognitive Impairment, Mild Dementia, Parkinson Disease, Lewy Body Disease

Intervention / Treatment
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* Drug: Placebo Oral Capsule
* Drug: NYX-458


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent Diagnosis of Parkinson's disease and mild cognitive impairment or mild dementia OR diagnosis of mild cognitive impairment or mild dementia with Lewy bodies Presence of subjective cognitive complaints by the patient Verifiable impairment, as defined a CGI-S (Clinical Global Impression-Severity) score of at least 3 (mildly ill). Score on the MoCA (Montreal Cognitive Assessment) between 15 and 25, inclusive. Stable anti-parkinsonian regimen (if applicable) Has a study partner who can accompany the subject at specified study visits Exclusion Criteria: Clinically meaningful motor complications Current use of medications with primarily central nervous system activities Other clinically significant medical histories that may interfere with completing the study.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Matching placebo Capsules | Drug: Placebo Oral Capsule<br>* Matching placebo capsules.<br>|
| Experimental: NYX-458 30 mg<br>Single oral dose taken daily for 12 weeks. | Drug: NYX-458<br>* NYX-458 is a small molecule that modulates the N-methyl-D-aspartate receptor (NMDAR).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in physical examination | Physical examination | Subjects will be followed up to 14 days post-dose | 
| Rates of adverse events and serious adverse events | Adverse events and serious adverse events | Subjects will be followed up to 14 days post-dose | 
| Rates of early termination due to adverse events | Early termination due to adverse events | Subjects will be followed up to 14 days post-dose | 
| Change from baseline in vital signs, clinical laboratory values, and electrocardiogram results | Vital signs, clinical laboratory values, and electrocardiogram results | Subjects will be followed up to 14 days post-dose | 
| Change from baseline dissociative effects, psychosis, and hallucinatory symptoms as measured by the Neuropsychiatric Inventory (NPI-12) | Neuropsychiatric Inventory (NPI-12) - NPI-12 assesses 12 behavioral domains common in dementia. Higher scores indicate more severe illness. | Subjects will be followed up to 14 days post-dose | 
| Change from baseline in suicidal ideation and behavior as measured by the Sheehan Suicidality Tracking Scale (S-STS) | Sheehan Suicidality Tracking Scale (S-STS) is a 16-item scale that assesses the seriousness of suicidality phenomena on a likert-type scale (0 to 4) ranging from 0 = not at all to 4 = extremely | Subjects will be followed up to 14 days post-dose | 
| Change from baseline in motor complications as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 4 | Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 4 includes 6 items assessing motor complications, higher scores indicate more serious illness. | Subjects will be followed up to 14 days post-dose | 
| Change in total score of the Sheehan Suicidality Tracking Scale (S-STS) | Sheehan Suicidality Tracking Scale (S-STS) is a 16-item scale that assesses the seriousness of suicidality phenomena on a likert-type scale (0 to 4) ranging from 0 = not at all to 4 = extremely | Subjects will be followed up to 14 days post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the One Back test | The One Back test is a measure of working memory | Week 12 | 
| Change from baseline in the Two Back test | The Two Back test is a measure of working memory | Week 12 | 
| Change from baseline in the Groton Maze Learning Test | The Groton Maze Learning test is a measure of problem solving and reasoning | Week 12 | 
| Change from baseline in the Identification Test | The Identification test is a measure of visual attention | Week 12 | 
| Change from baseline in the International Shopping List Test | The International Shopping List test is a measure of verbal learning | Week 12 | 
| Change from baseline on Continuous Paired Associate Learning Test | The Continuous Paired Associate Learning test is a measure of visual associate memory | Week 12 |