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

• ClinicalTrials.gov Identifier: NCT04148391
• Recruitment Status: Active, not recruiting
• First Posted: November 1, 2019
• Last Update Posted: October 27, 2022
• Sponsor: Aptinyx
• Collaborators: CogState Ltd.; Worldwide Clinical Trials
• Information provided by (Responsible Party): Aptinyx

Tracking Information

• First Submitted Date: October 30, 2019
• First Posted Date: November 1, 2019
• Last Update Posted Date: October 27, 2022
• Actual Study Start Date: November 14, 2019
• Estimated Primary Completion Date: December 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 25, 2021)

• Change from baseline in physical examination [ Time Frame: Subjects will be followed up to 14 days post-dose ]
  Physical examination
• Rates of adverse events and serious adverse events [ Time Frame: Subjects will be followed up to 14 days post-dose ]
  Adverse events and serious adverse events
• Rates of early termination due to adverse events [ Time Frame: Subjects will be followed up to 14 days post-dose ]
  Early termination due to adverse events
• Change from baseline in vital signs, clinical laboratory values, and electrocardiogram results [ Time Frame: Subjects will be followed up to 14 days post-dose ]
  Vital signs, clinical laboratory values, and electrocardiogram results
• Change from baseline dissociative effects, psychosis, and hallucinatory symptoms as measured by the Neuropsychiatric Inventory (NPI-12) [ Time Frame: Subjects will be followed up to 14 days post-dose ]
  Neuropsychiatric Inventory (NPI-12) - NPI-12 assesses 12 behavioral domains common in dementia. Higher scores indicate more severe illness.
• Change from baseline in suicidal ideation and behavior as measured by the Sheehan Suicidality Tracking Scale (S-STS) [ Time Frame: Subjects will be followed up to 14 days post-dose ]
  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
• Change from baseline in motor complications as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 4 [ Time Frame: Subjects will be followed up to 14 days post-dose ]
  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.
• Change in total score of the Sheehan Suicidality Tracking Scale (S-STS) [ Time Frame: Subjects will be followed up to 14 days post-dose ]
  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

• Original Primary Outcome Measures (submitted: October 30, 2019): Number of Subjects With Adverse Events [ Time Frame: Subjects will be followed up to 14 days post-dose ]

Current Secondary Outcome Measures (submitted: March 25, 2021)

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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: NYX-458 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson's Disease or Lewy Body Dementia (Cognition, Memory, Attention, Thinking)
• Official Title: 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
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Mild Cognitive Impairment
• Mild Dementia
• Parkinson Disease
• Lewy Body Disease

Intervention

• Drug: Placebo Oral Capsule
  Matching placebo capsules.
• Drug: NYX-458
  NYX-458 is a small molecule that modulates the N-methyl-D-aspartate receptor (NMDAR).

Study Arms

• Placebo Comparator: Placebo
  Matching placebo Capsules
  Intervention: Drug: Placebo Oral Capsule
• Experimental: NYX-458 30 mg
  Single oral dose taken daily for 12 weeks.
  Intervention: Drug: NYX-458

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 26, 2022): 99
• Original Estimated Enrollment (submitted: October 30, 2019): 135
• Estimated Study Completion Date: December 30, 2022
• Estimated Primary Completion Date: December 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04148391
• Other Study ID Numbers: NYX-458-2006
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Aptinyx
• Original Responsible Party: Same as current
• Current Study Sponsor: Aptinyx
• Original Study Sponsor: Same as current

Collaborators

• CogState Ltd.
• Worldwide Clinical Trials

• Investigators: Not Provided
• PRS Account: Aptinyx
• Verification Date: October 2022