A Study to Evaluate the Safety and Tolerability of SAGE-718 in Participants With Mild Cognitive Impairment or Mild Dementia Due to Alzheimer's Disease (AD)

An Open-Label Evaluation of the Safety and Tolerability of SAGE-718 in Participants With Mild Cognitive Impairment or Mild Dementia Due to Alzheimer's Disease

The primary purpose of this study is to evaluate the safety and tolerability of SAGE-718 and its effects on cognitive and neuropsychiatric symptoms in participants with mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease (AD).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85044
      • Sage Investigational Site
  • California
    • Redlands, California, United States, 92374
      • Sage Investigational Site
  • Florida
    • Miami, Florida, United States, 33137
      • Sage Investigational Site
    • St. Petersburg, Florida, United States, 33713
      • Sage Investigational Site
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Sage Investigational Site
    • Decatur, Georgia, United States, 30033
      • Sage Investigational Site
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • Sage Investigational Site
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Sage Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Sage Investigational Site
  • Ohio
    • North Canton, Ohio, United States, 44720
      • Sage Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant meets the following criteria for MCI or mild dementia due to AD at Screening: has a memory complaint, has clinical dementia rating (CDR) score of 0.5 to 1.0 (inclusive) with a memory box score ≥0.5, has essentially preserved activities of daily living
2. Participant has a score of 15 to 24 (inclusive) on the Montreal Cognitive Assessment at Screening
3. Participant has normal premorbid intelligence quotient (IQ) at Screening
4. Participant has a study partner who is reliable, competent, at least 18 years of age, willing to be available to the study center by phone, support study-specific activities, and accompany the participant to study visits as needed

Exclusion Criteria:

1. Participant has any medical or neurological condition (other than AD) that might be contributing to the participant's cognitive impairment or history of cognitive decline
2. Participant has 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
3. Participant has a history, presence, and/or current evidence of a clinically-significant intracranial abnormality (eg, stroke, hemorrhage, space-occupying lesion) that could account for the observed cognitive impairment (excluding abnormalities consistent with underlying AD pathology)
4. Participant has a history of possible or probable cerebral amyloid angiopathy, according to the Boston Criteria
5. Participant has a history of seizures or epilepsy, with the exception of a single episode of febrile seizures in childhood
6. Participant has current or recent suicidality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAGE-718; Participants received SAGE-718 3 mg oral tablets, once daily in the morning for 14 days.	Drug: SAGE-718; SAGE-718 oral tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	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 the 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.	From first dose of study drug up to last follow up visit (up to 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least One Potentially Clinically Significant (PCS) Change in Vital Signs Measurements	PCS changes for vital signs included: Supine Systolic Blood Pressure (SBP) >180 millimeters of mercury (mmHg), SBP decrease from baseline of ≥ 30 mmHg, standing 1-minute SBP >180 mmHg, standing 3 minutes SBP decrease from baseline of ≥ 30 mmHg, Supine diastolic BP (DBP) decrease from baseline of ≥ 20 mmHg, standing 1-minute DBP decrease from baseline of ≥ 20 mmHg, standing 1-minute DBP increase from baseline of ≥ 20 mmHg, standing 3-minute DBP increase from baseline of ≥ 20 mmHg, orthostatic SBP: supine-1 minute standing ≥ 20 mmHg and supine-3 minute standing ≥ 20 mmHg, orthostatic DBP: supine-1 minute standing ≥ 10 mmHg and supine-3 minute standing ≥ 10 mmHg. Percentage of participants with at least one PCS change in vital signs measurements were reported.	From first dose of study drug up to last follow-up visit (up to 28 days)
Percentage of Participants With at Least One Potentially Clinically Significant Change in Laboratory Assessments	PCS changes for laboratory assessments included: hematology: hematocrit- male low (<0.385 fractions of 1), hemoglobin male low (<115 grams per liter [g/L]) and biochemistry: glucose high (>13.9 millimoles per liter [mmol/L]), potassium low (<3.3 mmol/L), blood urea nitrogen high (>10.71 mmol/L)., Percentage of participants with at least one PCS change in laboratory assessments were reported.	From first dose of study drug up to last follow-up visit (up to 28 days)
Percentage of Participants With at Least One Potentially Clinically Significant Change in Electrocardiogram (ECG) Measurements	PCS changes for ECG measurements included: QTcF Interval >450 to ≤480 milliseconds (msec), >480 to ≤500 msec, and ≥30 to ≤60 msec increase from baseline. Percentage of participants with at least one PCS change in ECG measurements were reported.	From first dose of study drug up to last follow-up visit (up to 28 days)
Percentage of Participants With Suicidal Ideation or Behavior Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)	The C-SSRS scale assesses the lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB). 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 (with score range 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' for suicidal ideation or behavior were reported.	Up to Day 28

Collaborators and Investigators

• Sponsor: Supernus Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2020
• Primary Completion (Actual): September 28, 2021
• Study Completion (Actual): September 28, 2021

Study Registration Dates

• First Submitted: October 20, 2020
• First Submitted That Met QC Criteria: October 20, 2020
• First Posted (Actual): October 26, 2020

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 11, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease
• Other Study ID Numbers: 718-CNA-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