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

Sage Therapeutics

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Essential Tremor

Treatments: Drug: SAGE-324

Study type: Interventional

Funder types: Industry

Identifiers

NCT05366751

324-ETD-303

Details and patient eligibility

About

The primary purpose of this study is to evaluate the long-term safety and tolerability of SAGE-324 in participants with essential tremor (ET).

Enrollment: 97 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Participant is in good physical health and has no clinically significant findings (excluding ET) that may impact their ability to participate in the study, as determined by the investigator, on physical examination, 12-lead ECG, or clinical laboratory tests.

2. Participant has a clinician-confirmed diagnosis of ET in compliance with all the following criteria:

   1. Duration of at least 3 years
   2. Absence of other neurological signs, such as dystonia, ataxia, parkinsonism, task- and position-specific tremors, sudden tremor onset, or evidence of stepwise deterioration of tremor
   3. Absence of historical or clinical evidence of tremor with psychogenic origin (including, but not limited to, eating disorders and major depression)

3. Participant has completed the planned EOT visit and was not early terminated during the planned Treatment Period in another SAGE-324 study.

4. Participant is willing to limit use of alcohol to 2 units per day for males and 1 unit per day for females starting at least 1 week prior to Day 1 and through the End of Study (EOS) Visit.

   1. Participant will limit alcohol use to at least 2 hours before self-administration of IP in the evening.
   2. Participant will not use alcohol starting 24 hours prior to scheduled in-clinic study visits until all assessments have been completed.

5. Participant is willing to maintain prestudy consumption of products that contain nicotine starting at least 1 week prior to Day 1 and through EOS Visit.

Exclusion criteria

1. Participant has presence of alcohol withdrawal state.
2. Participant has had direct or indirect injury or trauma to the nervous system within 3 months before the onset of tremor.
3. Participant is taking and unable to discontinue the use of primidone at least 7 days prior to administration of the first dose of SAGE-324.
4. Participant has a history (within 3 years of Screening) or ongoing oncologic disease, excluding skin cancers (squamous or basal cell carcinoma) for which treatment has been completed and any carcinoma in situ.
5. Participant has an ongoing clinically relevant medical or psychiatric condition that, in the judgment of the investigator, is not well managed and poses a risk for participation in the study.
6. Participant has history of substance dependence and/or abuse prior to Screening, has a positive screen for drugs of abuse at Screening or predose on Day 1, (unless prescribed) or has a positive screen for alcohol or cotinine predose on Day 1. Participants with nicotine use disorder that impacts their tremor are excluded.
7. Participant has a known allergy to SAGE-324 or any excipient.
8. Female participant has a positive pregnancy test or confirmed pregnancy or is breastfeeding.
9. Participant has had exposure to another investigational drug or device within 30 days or 5 half-lives of the other investigational drug, whichever is longer, prior to the Day 1 visit and for the duration of the study.
10. Participant has a history of suicidal behavior within 2 years or answers "YES" to questions 3, 4, or 5 on the C-SSRS at Screening or at Day 1 or is currently at risk of suicide in the opinion of the investigator.
11. Participant has any condition or comorbidity that in the opinion of the investigator would limit or interfere with the participant's ability to complete or partake in the study.
12. Participant has used any known moderate or strong cytochrome P450 3A4 inhibitors and/or inducers within 14 days or 5 half-lives (whichever is longer) prior to Day 1 or consumed grapefruit juice, grapefruit, Seville oranges, or St. John's Wort or products containing these within 30 days prior to Day 1 and is unwilling to refrain from taking these medications or foods for the duration of dosing. Use of mild cytochrome inhibitors and/or inducers may be permitted.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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97 participants in 1 patient group

SAGE-324 60 mg

Experimental group

Description:

Participants will receive SAGE-324 oral tablets from Day 1 to the End of Treatment (EOT) Period at a starting dose of 15 milligrams (mg). The dose will be up titrated in 15 mg increments to 60 mg. In case of intolerable adverse events, the dose will be down titrated in 15 mg decrements.

Treatment:

Drug: SAGE-324