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 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.

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.

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.

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.

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.