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

Study Description

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

Condition or disease	Intervention/treatment	Phase
Mild Cognitive Impairment; Mild Dementia; Parkinson Disease; Lewy Body Disease	Drug: Placebo Oral Capsule; Drug: NYX-458	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 99 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 14, 2019
• Estimated Primary Completion Date: December 30, 2022
• Estimated Study Completion Date: December 30, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in physical examination [ Time Frame: Subjects will be followed up to 14 days post-dose ]
   Physical examination
2. 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
3. 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
4. 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
5. 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.
6. 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
7. 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.
8. 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

Secondary Outcome Measures :

1. Change from baseline in the One Back test [ Time Frame: Week 12 ]
   The One Back test is a measure of working memory
2. Change from baseline in the Two Back test [ Time Frame: Week 12 ]
   The Two Back test is a measure of working memory
3. 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
4. Change from baseline in the Identification Test [ Time Frame: Week 12 ]
   The Identification test is a measure of visual attention
5. Change from baseline in the International Shopping List Test [ Time Frame: Week 12 ]
   The International Shopping List test is a measure of verbal learning
6. 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

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Arizona

Aptinyx Clinical Site

Scottsdale, Arizona, United States, 85258

United States, California

Aptinyx Clinical Site

Fresno, California, United States, 93710

Aptinyx Clinical Site

Simi Valley, California, United States, 93065

United States, Florida

Aptinyx Clinical Site

Boca Raton, Florida, United States, 33486

Aptinyx Clinical Site

Bradenton, Florida, United States, 34209

Aptinyx Clinical Site

Miami Lakes, Florida, United States, 33016

Aptinyx Clinical Site

Miami, Florida, United States, 33122

Aptinyx Clinical Site

Miami, Florida, United States, 33165

Aptinyx Clinical Site

Miami, Florida, United States, 33173

Aptinyx Clinical Site

Miami, Florida, United States, 33176

Aptinyx Clinical Site

Orlando, Florida, United States, 32819

Aptinyx Clinical Site

Port Charlotte, Florida, United States, 33980

Aptinyx Clinical Site

Port Orange, Florida, United States, 32127

Aptinyx Clinical Site

Sunrise, Florida, United States, 33351

United States, Georgia

Aptinyx Clinical Site

Decatur, Georgia, United States, 30030

United States, Michigan

Aptinyx Clinical Site

Farmington Hills, Michigan, United States, 48334

United States, Minnesota

Aptinyx Clinical Site

Golden Valley, Minnesota, United States, 55427

United States, New Jersey

Aptinyx Clinical Site

Toms River, New Jersey, United States, 08755

United States, New York

Aptinyx Clinical Site

Poughkeepsie, New York, United States, 12601

United States, North Carolina

Aptinyx Clinical Site

Asheville, North Carolina, United States, 28806

United States, Ohio

Aptinyx Clinical Site

Dayton, Ohio, United States, 45459

United States, Oklahoma

Aptinyx Clinical Site

Tulsa, Oklahoma, United States, 74136

United States, Texas

Aptinyx Clinical Site

Round Rock, Texas, United States, 78681

Aptinyx Clinical Site

Sugar Land, Texas, United States, 77478

United States, Washington

Aptinyx Clinical Site

Bellevue, Washington, United States, 98007

Aptinyx Clinical Site

Spokane, Washington, United States, 99202

Sponsors and Collaborators

Aptinyx

CogState Ltd.

Worldwide Clinical Trials

More Information

• Responsible Party: Aptinyx
• ClinicalTrials.gov Identifier: NCT04148391
• Other Study ID Numbers: NYX-458-2006
• First Posted: November 1, 2019
• Last Update Posted: October 27, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Parkinson Disease; Dementia; Lewy Body Disease; Cognitive Dysfunction; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders