A Study to Evaluate the Long-term Safety and Tolerability of SAGE-324 in Participants With Essential Tremor

Number of participants with PCS postbaseline vital sign values are summarized for categories: supine and standing (1 and 3 minutes [min]) heart rate - maximum absolute value greater than (>)120 beats/min, minimum absolute value less than (<)40 beats/min. Supine and standing (1 and 3 min) SBP - maximum absolute value >180 millimeters of mercury (mmHg), minimum absolute value <90 mmHg, and increase or decrease from baseline of greater than or equal to (≥)30 mmHg; supine and standing (1 and 3 min) DBP - maximum absolute value >110 mmHg, minimum absolute value <50 mmHg, and increase or decrease from baseline of ≥20 mmHg. Only those categories where at least 1 participant met the PCS criterion at least once during postbaseline duration are reported.

Number of participants with PCS postbaseline values for QTcF are categorized as follows: absolute value >450 milliseconds (msec) and ≤480msec; absolute value >480 msec and ≤500msec; absolute value >500 msec and increase from baseline >30 and ≤60 msec; increase from baseline >60 msec. Only those categories where at least 1 participant met the PCS criterion at least once during postbaseline are reported.

Clinical laboratory test values are considered PCS if they meet either the lower-limit or higher-limit PCS criteria defined in the categories below. Number of participants with PCS laboratory values are summarized for clinical chemistry, liver function tests, hematology, and coagulation. Only those categories where at least 1 participant had a non-PCS value at Baseline and met the PCS criterion at least once during post-baseline are reported. Number analyzed is the number of participants with data available for analyses for the specified category.

ESS consists of 8 items where participants rate, on a 4-point scale of 0 (no chance of dozing) to 3 (high chance of dozing), their usual chances of dozing off or falling asleep while engaged in 8 different activities. ESS total score is sum of the 8 individual item scores and estimates a participant's average sleep propensity. ESS score can range from 0 to 24. ESS score ≥ 10 was used to indicate excessive daytime sleepiness. A higher score indicates more severe excessive daytime sleepiness. Baseline was defined as last non-missing measurement prior to the first dose of investigational product. All participants received SAGE-324 according to a predefined up-titration scheme. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.

C-SSRS scale consists of baseline evaluation that assesses lifetime experience of participant with suicidal ideation \& behavior, \& post-baseline evaluation that focuses on suicidality since last study visit. C-SSRS included 'yes'/'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1-5, with 5 being most severe). Higher score indicated more severe symptoms. If any of assessments in suicidal behavior are 'Yes', category is considered as 'Suicidal behavior'. If any of assessments in suicidal ideation is 'Yes', but all assessments in suicidal behavior are 'No', category is considered as 'Suicidal ideation'. Baseline: any 'Yes' in any question in suicidal ideation/behavior prior to first dose of investigational product, excluding lifetime assessments. Data is reported for only those timepoints where participants had at least one 'yes' response to suicidal ideation or suicidal behavior except at Baseline.

PWC is based on 35-item Penn Physician Withdrawal Checklist that was developed to measure benzodiazepine and benzodiazepine-like discontinuation symptoms. PWC-20 is a shorter version of Penn Physician Withdrawal Checklist and is made up of a list of 20 symptoms (e.g., loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability) that are rated on a scale of 0 (not present) to 3 (severe). Total scores can range from 0 to 60; higher scores indicating more severe symptoms. PWC-20 assessments were conducted at EOT and EOS to monitor for presence of potential withdrawal symptoms following discontinuation of IP. EOT was defined as first available assessment after last dose of study treatment and within 1 day of last dose of study treatment. All participants received SAGE-324 according to a predefined up-titration scheme. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.