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

Phase 3TerminatedNCT05366751

Sage Therapeutics97 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Essential Tremor

Interventions

SAGE-324DRUG

SAGE-324 oral tablets

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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 electrocardiogram (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 end of treatment (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 investigational product (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. 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.

Locations (38)

Outcomes

Primary Outcomes

Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as an AE with onset after 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.

Time frame: Up to 814 days

Secondary Outcomes

Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP)

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.

Time frame: Up to 814 days

Number of Participants With PCS Electrocardiogram (ECG) Findings for QT Corrected According to Fridericia's Formula [QTcF])

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.

Data from ClinicalTrials.gov

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Sage Investigational Site

Hoover, Alabama, United States

Sage Investigational Site

Scottsdale, Arizona, United States

Sage Investigational Site

Fountain Valley, California, United States

Sage Investigational Site

Fullerton, California, United States

Sage Investigational Site

Los Angeles, California, United States

Sage Investigational Site

Englewood, Colorado, United States

Sage Investigational Site

Boca Raton, Florida, United States

Sage Investigational Site

Bradenton, Florida, United States

Sage Investigational Site

Coral Springs, Florida, United States

Sage Investigational Site

Hollywood, Florida, United States

...and 28 more locations

Time frame: Up to 814 days

Number of Participants With PCS Laboratory Parameters

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.

Time frame: Up to 814 days

Change From Baseline in Epworth Sleepiness Scale (ESS) Score

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.

Time frame: Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 70, 84, 112, 140, 168, 274, 365, 456, 548, 639, 730, 765, End of Treatment [EOT] (anytime, up to Day 793), End of Study [EOS] (anytime, up to Day 814)

Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses

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.

Time frame: Baseline up to Day 814

Physician Withdrawal Checklist (PWC-20) Scale Total Score

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.

Time frame: EOT (anytime, up to Day 793), EOS (anytime, up to Day 814)