Clinical trial NCT05366751: A Study to Evaluate the Long-term Safety and Tolerability of SAGE-324 in Participants With Essential Tremor
Official title: An Open-label Study of the Long-term Safety and Tolerability of SAGE-324 in Participants With Essential Tremor
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Essential Tremor
Keywords: SAGE-324
Lead sponsor: Sage Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-05-09
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With at least One Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: Percentage of Participants With Change from Baseline in Vital Sign Parameters
timeFrame: Baseline up to approximately 5 years
measure: Percentage of Participants With Change from Baseline in Electrocardiogram (ECG) Parameters
timeFrame: Baseline up to approximately 5 years
measure: Percentage of Participants With Change from Baseline in Clinical Laboratory Parameters
timeFrame: Baseline up to approximately 5 years
measure: Percentage of Participants With Change from Baseline in Epworth Sleepiness Scale (ESS) Score
timeFrame: Baseline up to approximately 5 years
measure: Percentage of Participants With Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses
timeFrame: Baseline up to approximately 5 years
measure: Physician Withdrawal Checklist (PWC-20) Scale Score
timeFrame: Baseline up to approximately 5 years
Other outcomes:
Locations:
city: Hoover
country: United States
facility: Sage Investigational Site
state: Alabama
city: Scottsdale
country: United States
facility: Sage Investigational Site
state: Arizona
city: Fountain Valley
country: United States
facility: Sage Investigational Site
state: California
city: Fullerton
country: United States
facility: Sage Investigational Site
state: California
city: Los Angeles
country: United States
facility: Sage Investigational Site
state: California
city: Englewood
country: United States
facility: Sage Investigational Site
state: Colorado
city: Boca Raton
country: United States
facility: Sage Investigational Site
state: Florida
city: Bradenton
country: United States
facility: Sage Investigational Site
state: Florida
city: Coral Springs
country: United States
facility: Sage Investigational Site
state: Florida
city: Hollywood
country: United States
facility: Sage Investigational Site
state: Florida
city: Miami
country: United States
facility: Sage Investigational Site
state: Florida
city: Miami
country: United States
facility: Sage Investigational Site
state: Florida
city: Miami
country: United States
facility: Sage Investigational Site
state: Florida
city: Naples
country: United States
facility: Sage Investigational Site
state: Florida
city: Tampa
country: United States
facility: Sage Investigational Site
state: Florida
city: Winter Park
country: United States
facility: Sage Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Sage Investigational Site
state: Georgia
city: Decatur
country: United States
facility: Sage Investigational Site
state: Georgia
city: Kansas City
country: United States
facility: Sage Investigational Site
state: Kansas
city: Lexington
country: United States
facility: Sage Investigational Site
state: Kentucky
city: Shreveport
country: United States
facility: Sage Investigational Site
state: Louisiana
city: Boston
country: United States
facility: Sage Investigational Site
state: Massachusetts
city: Farmington Hills
country: United States
facility: Sage Investigational Site
state: Michigan
city: New York
country: United States
facility: Sage Investigational Site
state: New York
city: New York
country: United States
facility: Sage Investigational Site
state: New York
city: Asheville
country: United States
facility: Sage Investigational Site
state: North Carolina
city: Dayton
country: United States
facility: Sage Investigational Site
state: Ohio
city: Tulsa
country: United States
facility: Sage Investigational Site
state: Oklahoma
city: Memphis
country: United States
facility: Sage Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Sage Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: Sage Investigational Site
state: Texas
city: Houston
country: United States
facility: Sage Investigational Site
state: Texas
city: Katy
country: United States
facility: Sage Investigational Site
state: Texas
city: Round Rock
country: United States
facility: Sage Investigational Site
state: Texas
city: Fairfax
country: United States
facility: Sage Investigational Site
state: Virginia
city: Kirkland
country: United States
facility: Sage Investigational Site
state: Washington
city: Spokane
country: United States
facility: Sage Investigational Site
state: Washington
Study officials:
References: