Study to Evaluate SAGE-324 in Participants With Essential Tremor

Inclusion Criteria:

1. Diagnosis of ET, as defined by all of the following criteria:

• Isolated tremor syndrome consisting of bilateral upper limb action tremor

• At least 3 years duration

• With or without tremor in other locations (eg, head, voice, or lower limbs)

2. Absence of other neurological signs, such as dystonia, ataxia, or parkinsonism,isolated focal tremors (eg, voice, head), task- and position-specific tremors,sudden tremor onset, or evidence of stepwise deterioration of tremor.

3. Participant has the following:

• Scores of at least 12 in the combined TETRAS Performance Subscale Item 4 (upperlimb tremor) at both Screening and pre-dose on Day 1

• Scores of at least 6 in the total TETRAS Performance Subscale Item 4 score forthe dominant upper limb (the sum of the three items for either the right orleft upper limb, whichever is dominant) at both Screening and pre-dose on Day 1

4. Participant has a baseline TETRAS ADL Subscale score of at least 20 at Screening.

5. Willing to discontinue medications taken for the treatment of ET except propranololat least 14 days or 5 half-lives (whichever is longer) prior to receiving theinvestigational product (IP). Medications taken for the treatment of ET that werediscontinued prior to receiving IP may be resumed following Day 97. Participants inthe adjunct therapy cohort must be on a stable dose of propranolol (maximum totaldaily propranolol dose up to 320 mg allowed) for the treatment of ET from 3 monthsprior to Screening through Day 97 of the study.

6. Participant is willing to limit use of alcohol to 2 units per day for males and 1unit per day for females starting at least 1 week prior to Day 1 and through Day 97of the study.

7. Participant is willing to maintain prestudy consumption of products that containnicotine starting at least 1 week prior to Day 1 and through Day 97 of the study.

Exclusion Criteria:

1. Presence of known causes of enhanced physiological tremor.

2. Participant has had newly administered tremorgenic drugs (14 days or 5 half-lives [whichever is longer] prior to Day 1) or presence of alcohol withdrawal state.

3. Direct or indirect injury or trauma to the nervous system within 3 months before theonset of tremor.

4. Previous procedure for the treatment of ET, deep brain stimulation, brain lesioning,or magnetic resonance (MR) guided procedure, eg, MR-guided focused ultrasound. Useof Cala Trio bracelet for the treatment of ET from two weeks prior to Day 1 throughDay 97 is prohibited.

5. Participant has had botulinum toxin for treatment of ET within 6 months ofScreening.

6. Historical or clinical evidence of tremor with functional neurological syndromeorigin.

7. Participant currently requires propranolol treatment for a medical condition otherthan ET.

8. Participant has history of substance abuse or dependence prior to Screening, has apositive screen for drugs of abuse at Screening or predose on Day 1. Participantswith nicotine use disorder that impacts their tremor are excluded.