A Study to Evaluate the Effects of SAGE-718 in Participants With Parkinson's Disease Cognitive Impairment

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the effect of SAGE-718 on cognitive performance in participants with Parkinson's disease mild cognitive impairment (PD-MCI).

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of SAGE-718 in Parkinson's Disease Cognitive Impairment

Conditions
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Parkinson Disease, Cognitive Dysfunction

Intervention / Treatment
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* Drug: SAGE-718
* Drug: SAGE-718-matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the following criteria for PD-MCI: Have a confirmed diagnosis of idiopathic Parkinson's disease (PD) according to 2015 Movement Disorder Society (MDS) clinical diagnostic criteria and meet MDS Task Force criteria for MCI in PD (excluding requirement for United Kingdom PD Brain Bank diagnostic criteria). Meet the following criteria for MoCA: For participants meeting Level 1 PD-MCI criteria, have a Montreal Cognitive Assessment (MoCA) score of 20 to 25 (inclusive) at Screening; For participants meeting Level 2 PD-MCI criteria (within the past year), have a MoCA score of 18 to 25 (inclusive) at Screening. Meet criteria for modified Hoehn & Yahr Stage I to III (mild to moderate motor severity) at Screening. Have stable motor symptoms for at least 4 weeks prior to Screening, in the opinion of the investigator. Must be able to complete the Color Trails Test 1 (including the ability to follow rater redirection and correct errors), and, based on participant's performance and investigator's opinion, participant is expected to be capable of engaging in prolonged cognitive testing for the duration of the study. Exclusion Criteria: Have a diagnosis of dementia of any etiology, including but not limited to: Dementia with Lewy bodies, Alzheimer's dementia, and vascular dementia. Have any parkinsonism other than PD, including secondary parkinsonism or atypical parkinsonism. In the opinion of the investigator, be experiencing fluctuations in motor symptoms associated with PD that will interfere with completing study procedures. Have an ongoing central nervous system condition other than PD that in the opinion of the investigator could influence the outcome of the study. Have experienced significant psychotic symptoms, including hallucinations or delusions, within the past 3 months, in the opinion of the investigator. Have a history of brain surgery, deep brain stimulation, or any history of hospitalization due to a brain injury. Have a history, presence, and/or current evidence clinically relevant intracranial abnormality (e.g., stroke, hemorrhage, space-occupying lesion).

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAGE-718<br>Participants will receive SAGE-718 capsules, orally, once daily in the morning for 42 days. | Drug: SAGE-718<br>* Softgel capsules<br>|
| Placebo Comparator: Placebo<br>Participants will receive SAGE-718-matching placebo capsules, orally, once daily in the morning for 42 days. | Drug: SAGE-718-matching placebo<br>* Softgel capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Day 42 in the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding Test Score | WAIS-IV coding test is a valid and sensitive measure of cognitive dysfunction that correlates with real-world functional outcomes (e.g., the ability to accomplish everyday tasks) and recovery from functional disability used to assess processing speed. The participant is required to identify the symbols matched to numbers using a key and write in the symbol beneath the associated number. The total score ranges from 0 to 135 and is based on the total number of codes correctly completed over a 120-second time limit. Higher scores indicate better processing speed. Positive change from baseline indicates better processing speed. | Baseline up to Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with at Least One Treatment-Emergent Adverse Event (TEAE) and TEAEs by Severity |  | Up to Day 70 | 
| Number of Participants who Withdraw Due to Adverse Events (AEs) |  | Up to Day 70 |