A Study to Evaluate the Safety and Tolerability of SAGE-718 in Participants With Parkinson's Disease Mild Cognitive Impairment (PD-MCI)

An Open-Label Evaluation of the Safety and Tolerability of SAGE-718 in Participants With Parkinson's Disease Mild Cognitive Impairment

The primary purpose of this two-part study was to evaluate the safety and tolerability of SAGE-718 and its effects on cognitive, neuropsychiatric, and motor symptoms in participants with Parkinson's disease mild cognitive impairment (PD-MCI).

Study Overview

• Status: Completed
• Conditions: Parkinson Disease; Cognitive Dysfunction
• Intervention / Treatment: Drug: SAGE-718

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Sage Investigational Site
  • Florida
    • Port Charlotte, Florida, United States, 33980
      • Sage Investigational Site
    • West Palm Beach, Florida, United States, 33407
      • Sage Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Sage Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Meet the following criteria for PD-MCI: Have a confirmed diagnosis of idiopathic PD according to 2015 Movement Disorder Society (MDS) clinical diagnostic criteria; Meet MDS Task Force Criteria for MCI in PD.
2. Have a score of 20 to 25 (inclusive) on the Montreal Cognitive Assessment (MoCA) at Screening.
3. Meet criteria for Hoehn & Yahr Stage I to III (mild to moderate motor severity) at Screening.
4. Have stable motor symptoms for at least 4 weeks prior to screening, in the opinion of the investigator.

Exclusion Criteria:

1. Have a diagnosis of dementia of any etiology, including but not limited to: Dementia associated with PD (probable or possible), Dementia with Lewy Bodies, Alzheimer's Dementia, and Vascular Dementia.
2. Have any indication of parkinsonism other than idiopathic PD.
3. In the opinion of the investigator, be experiencing unpredictable fluctuations in motor and/or nonmotor symptoms associated with PD.
4. Have an ongoing central nervous system condition other than idiopathic PD, including active neurologic and/or nonremitted psychiatric disorders, in the opinion of the investigator.
5. Have a history of brain surgery, deep brain stimulation, a significant head injury causing loss of consciousness greater than 30 minutes, or hospitalization due to a brain injury.
6. Have experienced significant psychotic symptoms within the past 3 months, including those associated with PD medications, as determined by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: SAGE-718 3 mg; Participants received SAGE-718 3 milligrams (mg) tablets, once daily with food in the morning for 14 days.	Drug: SAGE-718; Oral tablets.
Experimental: Part B: SAGE-718 3 mg; Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 28 days.	Drug: SAGE-718; Oral tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)	An adverse event (AE) was any untoward medical occurrence in a participant administered with a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.	From first dose of study drug up to 28 days
Part B: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)	An AE was any untoward medical occurrence in a participant administered with a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.	From first dose of study drug up to 42 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A and B: Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements	Vital signs included temperature, respiratory rate, heart rate (supine and standing), systolic blood pressure (supine and standing) and diastolic blood pressure (supine and standing). Percentage of participants with clinically significant change in vital signs measurements which were deemed clinically significant by the investigator were reported.	From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B
Part A and B: Percentage of Participants With Clinically Significant Changes in Laboratory Assessments	Laboratory tests assessments included hematology, biochemistry, coagulation and urinalysis. Percentage of participants with clinically significant change in laboratory assessments which were deemed clinically significant by the investigator were reported.	From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B
Part A and B: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements	Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR interval, QRS duration, QT interval, and corrected QT interval by Fridericia [QTcF]). Percentage of participants with clinically significant change in ECG measurements which were deemed clinically significant by the investigator were reported.	From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B
Part A and B: Percentage of Participants With a Response of 'Yes' to Any Suicidal Ideation or Suicidal Behaviors Item Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)	The C-SSRS scale consisted of a baseline evaluation (at screening) that assessed the lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and a postbaseline evaluation that focused on suicidality since the last study visit. The C-SSRS included "yes" or "no"' responses for assessment of suicidal ideation and behavior as well as numeric ratings for the severity of ideation, if present (from 1 to 5, with 5 being the most severe). The C-SSRS SI items involved wish to be dead, non-specific active suicidal thoughts, active SI with any methods, active SI with some intent and active SI with a specific plan. The C-SSRS SB items involved preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal) and completed suicide. Percentage of participants with a response of 'yes' are reported for both suicidal ideation and behavior in this OM.	From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B

Collaborators and Investigators

• Sponsor: Sage Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2020
• Primary Completion (Actual): March 25, 2022
• Study Completion (Actual): March 25, 2022

Study Registration Dates

• First Submitted: July 15, 2020
• First Submitted That Met QC Criteria: July 15, 2020
• First Posted (Actual): July 17, 2020

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Parkinson's Disease; Cognitive Dysfunction; SAGE-718
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Parkinson Disease; Cognitive Dysfunction
• Other Study ID Numbers: 718-CNP-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No