Trial Outcomes & Findings for 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) (NCT NCT04602624)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

From first dose of study drug up to last follow up visit (up to 28 days)

Results posted on

2025-09-15

Participant Flow

Participants were enrolled at investigative sites in the United States from 07 December 2020 to 28 September 2021.

A total of 58 participants were screened, of which 26 participants were enrolled to receive SAGE-718.

Participant milestones

Participant milestones
Measure	SAGE-718 Participants received SAGE-718 3 mg oral tablets, once daily in the morning for 14 days.
Overall Study STARTED	26
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	SAGE-718 Participants received SAGE-718 3 mg oral tablets, once daily in the morning for 14 days.
Overall Study Protocol Deviation	1
Overall Study Withdrawal by Participant	1

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SAGE-718 n=26 Participants Participants received SAGE-718 3 mg oral tablets, once daily in the morning for 14 days.
Age, Continuous	67.0 years STANDARD_DEVIATION 9.11 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	21 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first dose of study drug up to last follow up visit (up to 28 days)

Population: Safety Set included all participants who were administered IP.

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.

Outcome measures

Outcome measures
Measure	SAGE-718 n=26 Participants Participants received SAGE-718 3 mg oral tablets, once daily in the morning for 14 days.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	7 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to last follow-up visit (up to 28 days)

Population: Safety Set included all participants who were administered IP. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.

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.

Outcome measures

Outcome measures
Measure	SAGE-718 n=25 Participants Participants received SAGE-718 3 mg oral tablets, once daily in the morning for 14 days.
Percentage of Participants With at Least One Potentially Clinically Significant (PCS) Change in Vital Signs Measurements	64.0 percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug up to last follow-up visit (up to 28 days)

Population: Safety Set included all participants who were administered IP. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.

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.

Outcome measures

Outcome measures
Measure	SAGE-718 n=25 Participants Participants received SAGE-718 3 mg oral tablets, once daily in the morning for 14 days.
Percentage of Participants With at Least One Potentially Clinically Significant Change in Laboratory Assessments Hematology	12.0 percentage of participants
Percentage of Participants With at Least One Potentially Clinically Significant Change in Laboratory Assessments Biochemistry	16.0 percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug up to last follow-up visit (up to 28 days)

Population: Safety Set included all participants who were administered IP. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.

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.

Outcome measures

Outcome measures
Measure	SAGE-718 n=25 Participants Participants received SAGE-718 3 mg oral tablets, once daily in the morning for 14 days.
Percentage of Participants With at Least One Potentially Clinically Significant Change in Electrocardiogram (ECG) Measurements	32.0 percentage of participants

SECONDARY outcome

Timeframe: Up to Day 28

Population: Safety Set included all participants who were administered IP.

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.

Outcome measures

Outcome measures
Measure	SAGE-718 n=26 Participants Participants received SAGE-718 3 mg oral tablets, once daily in the morning for 14 days.
Percentage of Participants With Suicidal Ideation or Behavior Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)	0 percentage of participants

Adverse Events

SAGE-718

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	SAGE-718 n=26 participants at risk Participants received SAGE-718 3 mg oral tablets, once daily in the morning for 14 days.
Gastrointestinal disorders Constipation	7.7% 2/26 • Screening up to last follow-up visit (approximately 49 days) Safety Set included all participants who were administered IP.
Gastrointestinal disorders Nausea	3.8% 1/26 • Screening up to last follow-up visit (approximately 49 days) Safety Set included all participants who were administered IP.
Infections and infestations Urinary tract infection	3.8% 1/26 • Screening up to last follow-up visit (approximately 49 days) Safety Set included all participants who were administered IP.
Nervous system disorders Headache	7.7% 2/26 • Screening up to last follow-up visit (approximately 49 days) Safety Set included all participants who were administered IP.
Psychiatric disorders Agitation	3.8% 1/26 • Screening up to last follow-up visit (approximately 49 days) Safety Set included all participants who were administered IP.
Psychiatric disorders Insomnia	3.8% 1/26 • Screening up to last follow-up visit (approximately 49 days) Safety Set included all participants who were administered IP.

Additional Information

Medical Monitor

Sage Therapeutics

Phone: (617) 299-8380

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI can either be a party and subject to the same restrictions as the institution, or if not a party, the restrictions are described on the face of the contract (i.e., PI is a contractor of the institution; PI is part of a larger group of study personnel; institution has contracted with or otherwise bound all study personnel under confidentiality obligations and requirements to vest intellectual property to the institution).
Publication restrictions are in place

Restriction type: OTHER