Essential TremorPhase 2NCT04305275
A Study to Evaluate the Efficacy, Safety, and Tolerability of SAGE-324 in Participants With Essential Tremor
A Phase 2 study testing SAGE-324 in people with Essential Tremor, run by Sage Therapeutics at 27 sites in United States.
Trial summary
This is a phase 2, double-blind, placebo-controlled study to evaluate the safety and efficacy of SAGE-324 compared to placebo on upper limb (UL) tremor reduction in individuals with essential tremor (ET). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Essential Tremor
- What is being tested?
- SAGE-324
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 27 sitesUnited States
- Study dates
- 19 May 2020to 15 Feb 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant has a diagnosis of ET, defined as isolated tremor syndrome consisting of bilateral upper limb action tremor for at least 3 years prior to screening, with or without tremor in other locations and absence of other neurological signs, such as dystonia, ataxia, or parkinsonism, isolated focal tremors (e.g., voice, head), task- and position-specific tremors, sudden tremor onset or evidence of step-wise deterioration of tremor.
- Participant scores at least 1.5 for each of the six items that comprise the combined total upper limb the essential tremor rating assessment scale (TETRAS) (total performance subscale part 4) with the total score for the dominant upper limb (the sum of the three items for either the right or left upper limb, whichever is dominant) being at least 5.5, at both Screening and pre-dose on Day 1.
- Participant is willing to discontinue medications taken for the treatment of ET within 14 days or 5 half-lives prior to receiving investigational product (IP). Medications taken for the treatment of ET that were discontinued prior to receiving IP may be resumed following Day 29.
- Participant has no clinically significant findings, as determined by the investigator, on Screening and pre-dose Day 1 physical examination including mental state examination (MSE) and neurologic examination, 12-lead electrocardiogram (ECG), or screening clinical laboratory tests.
Who cannot join
- Participant has a presence of known causes of enhanced physiological tremor.
- Participant has had recent exposure (14 days prior to Day 1) to tremorgenic drugs.
- Participant has had direct or indirect injury or trauma to the nervous system within 3 months before the onset of tremor.
- Participant has had a previous procedure for the treatment of ET, deep brain stimulation, brain lesioning, or magnetic resonance (MR)-guided procedure, e.g., MR-guided focused ultrasound.
- Participant has historical or clinical evidence of tremor with psychogenic origin (including but not limited to eating disorders, major depression, etc.).
- Participant has history of suicidal behavior within 2 years or answers "YES" to questions 3, 4, or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or at Day 1 or is currently at risk for suicide in the opinion of the investigator.
Show all 9Show fewer
- Participant has used any known moderate or strong cytochrome P450 3A4 and/or inducers within 14 days or 5 half-lives (whichever is longer) prior to Day 1 or consumed grapefruit juice, grapefruit, Seville oranges, pomegranates, tangelos, or St. John's Wort or products containing these within 30 days prior to Day 1. Use of mild cytochrome inhibitors and/or inducers may be permitted.
- Participant has concurrent or recent exposure (14 days or 5 half-lives, whichever is longer, prior to the Day 1 visit) to sedative/hypnotic drugs, stimulants, highly-caffeinated beverages or dietary supplements containing high doses of caffeine, or recent increase above regular daily consumption of caffeine.
- Participant currently uses or has used within 14 days or 5 half-lives (whichever is longer) prior to Day 1, any prescription or over-the-counter medication that is a substrate of the organic anion transporting polypeptide 1B1 (OATP1B1) transporter.
Trial locations and contacts
27 sites in 1 country.
27 sites in 1 country
United States27 sites
Sage Investigational Site
Asheville, North Carolina, 28806
Sage Investigational Site
Boca Raton, Florida, 33486
Sage Investigational Site
Cincinnati, Ohio, 45212
Sage Investigational Site
Dayton, Ohio, 45417
Sage Investigational Site
Decatur, Georgia, 30030
Sage Investigational Site
Englewood, Colorado, 80113
Sage Investigational Site
Farmington Hills, Michigan, 48334
Sage Investigational Site
Fresno, California, 93710
Sage Investigational Site
Gainesville, Florida, 32608
Sage Investigational Site
Hollywood, Florida, 33024
Sage Investigational Site
Houston, Texas, 77030
Sage Investigational Site
Huntington, West Virginia, 25701
Sage Investigational Site
Kansas City, Kansas, 66160
Sage Investigational Site
Long Beach, California, 90806
Sage Investigational Site
Miami, Florida, 33136
Sage Investigational Site
Miami, Florida, 33176
Sage Investigational Site
New York, New York, 10032
Sage Investigational Site
Phoenix, Arizona, 85258
Sage Investigational Site
Port Charlotte, Florida, 33980
Sage Investigational Site
Richmond, Virginia, 23229
Sage Investigational Site
Rogers, Arkansas, 72758
Sage Investigational Site
Savannah, Georgia, 31406
Sage Investigational Site
Spokane, Washington, 99202
Sage Investigational Site
Springfield, Illinois, 62702
Sage Investigational Site
St. Petersburg, Florida, 33713
Sage Investigational Site
Tampa, Florida, 33609
Sage Investigational Site
Tulsa, Oklahoma, 74136
About this study
Official title: A Phase 2, Double-Blind, Placebo-controlled, Randomized Study Evaluating the Efficacy, Safety, and Tolerability of Sage-324 in the Treatment of Individuals With Essential Tremor
This is a phase 2, double-blind, placebo-controlled study to evaluate the safety and efficacy of SAGE-324 compared to placebo on upper limb (UL) tremor reduction in individuals with essential tremor (ET).
- Conditions
- Essential Tremor
- Being tested
- SAGE-324, SAGE-324 Placebo
- Keywords
- Essential Tremor, SAGE-324
- Medical subject headings
- Essential Tremor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAGE-324Drug
SAGE-324 oral tablet
SAGE-324 PlaceboDrug
SAGE-324 matched placebo oral tablet
| Study group | Role | What they receive |
|---|---|---|
| SAGE-324 60 mg | Experimental | Participants received SAGE-324, 60 milligrams (mg), oral tablets, once daily (QD), in the morning for 28 days. Receives: Drug: SAGE-324 |
| SAGE-324 Matched Placebo | Placebo comparator | Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days. Receives: Drug: SAGE-324 Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score on Day 29
The Essential Tremor Rating Assessment Scale (TETRAS) is a clinical evaluation of essential tremor. The TETRAS performance subscale upper limb tremor score is a component of TETRAS. The TETRAS performance subscale upper limb tremor total score is the sum of the TETRAS individual item scores from both arms of the body. The TETRAS individual item score included TETRAS Performance Subscale items 4a, 4b, and 4c scores [4a: limbs extended forward maneuver, 4b: wing-beating (elbows flexed) maneuver, and 4c: kinetic (finger-nose-finger) maneuver] scores from both arms of the body. Each individual item score ranges from 0 to 4; with 0 to 12 being the score range for each arm of the body. The total upper limb score combined for both arms ranges from 0 to 24. Higher scores=more severe tremor. A negative change from baseline =improvement. Mixed model repeated measures (MMRM) was used for the analysis.
Measured: Baseline, Day 29
Secondary outcomes (5)
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42
TETRAS is a clinical evaluation of essential tremor. The TETRAS performance subscale upper limb tremor score is a component of TETRAS. The TETRAS performance subscale upper limb tremor total score is the sum of the TETRAS individual item scores from both arms of the body. The TETRAS individual item score included TETRAS Performance Subscale items 4a, 4b, and 4c scores [4a: limbs extended forward maneuver, 4b: wing-beating (elbows flexed) maneuver, and 4c: kinetic (finger-nose-finger) maneuver] scores from both arms of the body. Each individual item score ranges from 0 to 4; with 0 to 12 being the score range for each arm of the body. The total upper limb score combined for both arms ranges from 0 to 24. Higher scores=more severe tremor. A negative change from baseline =improvement. MMRM was used for the analysis.
Measured: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, and 42
Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42
Kinesia ONE™ measures three-dimensional motion converted to scores. Motion in both arms were captured. The accelerometer-based Kinesia ONE individual scores is the sum of the individual item scores across both arms of the body. The individual items included forward outstretched postural tremor, lateral "wing beating" postural tremor, and kinetic tremor scores from both arms of the body. Each individual item score ranges from 0 (no tremor) to 4 (severe tremor); with 0 to 12 being the score range for each arm of the body. The Kinesia ONE total score combined for both arms ranges from 0 to 24. Higher scores=more tremors/greater tremor amplitude. A negative change from baseline indicates improvement. MMRM was used for the analysis.
Measured: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, 29, and 42
Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42
The ADL subscale assesses how ET impacts typical activities of daily living (speech, eating, drinking, dressing, personal hygiene, writing, occupational impairment, social impact, and activities affected by UL tremor. It consists of 12 items, each rated from 0 (normal activity) to 4 (severe abnormality). The overall ADL score, calculated as the sum of subscale items ranges from 0 to 48. Higher scores indicate greater tremor severity, while a negative change from baseline indicates improvement. MMRM was used for the analysis.
Measured: Baseline, Days 8, 15, 22, 29, and 42
Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42
The total performance score is based on the overall rating of tremor amplitude in the voice, limbs, head, face, and trunk while performing pre-specified tasks, and functional task capabilities (handwriting, spiral drawing, and holding a pen over a dot). Each of these items is rated from 0 (no tremor) to 4 (severe tremor) with an overall performance score of 0 to 64, calculated as the sum of subscale items. Higher scores indicate greater tremor severity. A negative change from baseline indicates improvement. MMRM was used for the analysis.
Measured: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, 29, and 42
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with the treatment. A TEAE was defined as an AE with onset after the start of investigational product (IP), or any worsening of a preexisting medical condition/AE with onset after the start of IP and throughout the study.
Measured: From the first dose of the study drug up to the end of the study (i.e., up to approximately 42 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2020
- Study start19 May 2020
- Primary completion1 Feb 2021
- Study completion15 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Essential TremorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sage Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04305275
- Sponsor's protocol ID
- 324-ETD-201
- Status last verified
- Mar 2024
- First submitted
- 10 Mar 2020
- Last updated
- 17 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Double-Blind, Placebo-controlled, Randomized Study Evaluating the Efficacy, Safety, and Tolerability of Sage-324 in the Treatment of Individuals With Essential Tremor
- ClinicalTrials.gov ID
- NCT04305275
- Acronym / sponsor ID
- 324-ETD-201
- Conditions
- Essential Tremor
- Keywords
- Essential Tremor, SAGE-324
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Sage TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 19 May 2020 (actual)
- Primary completion
- 1 Feb 2021 (actual)
- Study completion
- 15 Feb 2021 (actual)
- First posted
- 12 Mar 2020 (actual)
- Results
- Posted 17 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 2, double-blind, placebo-controlled study to evaluate the safety and efficacy of SAGE-324 compared to placebo on upper limb (UL) tremor reduction in individuals with essential tremor (ET).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SAGE-324 60 mg | Experimental | Drug: SAGE-324Participants received SAGE-324, 60 milligrams (mg), oral tablets, once daily (QD), in the morning for 28 days. |
| SAGE-324 Matched Placebo | Placebo comparator | Drug: SAGE-324 PlaceboParticipants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Participant has a diagnosis of ET, defined as isolated tremor syndrome consisting of bilateral upper limb action tremor for at least 3 years prior to screening, with or without tremor in other locations and absence of other neurological signs, such as dystonia, ataxia, or parkinsonism, isolated focal tremors (e.g., voice, head), task- and position-specific tremors, sudden tremor onset or evidence of step-wise deterioration of tremor.
- Participant scores at least 1.5 for each of the six items that comprise the combined total upper limb the essential tremor rating assessment scale (TETRAS) (total performance subscale part 4) with the total score for the dominant upper limb (the sum of the three items for either the right or left upper limb, whichever is dominant) being at least 5.5, at both Screening and pre-dose on Day 1.
- Participant is willing to discontinue medications taken for the treatment of ET within 14 days or 5 half-lives prior to receiving investigational product (IP). Medications taken for the treatment of ET that were discontinued prior to receiving IP may be resumed following Day 29.
- Participant has no clinically significant findings, as determined by the investigator, on Screening and pre-dose Day 1 physical examination including mental state examination (MSE) and neurologic examination, 12-lead electrocardiogram (ECG), or screening clinical laboratory tests.
Key exclusion criteria (9 listed)
- Participant has a presence of known causes of enhanced physiological tremor.
- Participant has had recent exposure (14 days prior to Day 1) to tremorgenic drugs.
- Participant has had direct or indirect injury or trauma to the nervous system within 3 months before the onset of tremor.
- Participant has had a previous procedure for the treatment of ET, deep brain stimulation, brain lesioning, or magnetic resonance (MR)-guided procedure, e.g., MR-guided focused ultrasound.
- Participant has historical or clinical evidence of tremor with psychogenic origin (including but not limited to eating disorders, major depression, etc.).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SAGE-324SAGE-324 oral tablet | Drug | SAGE-324 60 mg |
| SAGE-324 PlaceboSAGE-324 matched placebo oral tablet | Drug | SAGE-324 Matched Placebo |
Primary outcome
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score on Day 29
Time frame: Baseline, Day 29
The Essential Tremor Rating Assessment Scale (TETRAS) is a clinical evaluation of essential tremor. The TETRAS performance subscale upper limb tremor score is a component of TETRAS. The TETRAS performance subscale upper limb tremor total score is the sum of the TETRAS individual item scores from both arms of the body. The TETRAS individual item score included TETRAS Performance Subscale items 4a, 4b, and 4c scores [4a: limbs extended forward maneuver, 4b: wing-beating (elbows flexed) maneuver, and 4c: kinetic (finger-nose-finger) maneuver] scores from both arms of the body. Each individual item score ranges from 0 to 4; with 0 to 12 being the score range for each arm of the body. The total upper limb score combined for both arms ranges from 0 to 24. Higher scores=more severe tremor. A negative change from baseline =improvement. Mixed model repeated measures (MMRM) was used for the analysis.
5 secondary outcomes
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42
Time frame: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, and 42
Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42
Time frame: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, 29, and 42
Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42
Time frame: Baseline, Days 8, 15, 22, 29, and 42
Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42
Time frame: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, 29, and 42
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From the first dose of the study drug up to the end of the study (i.e., up to approximately 42 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.
Related trials for Essential Tremor
Active, not recruitingObservational study
Identifying Markers of Disease Subtypes and Disease Progression in the Syndrome of Essential Tremor
Essential Tremor
RecruitingPhase 2
Study of AGN-151607-DP to Assess Adverse Events and Change in Disease Activity in Adult Participants With Upper Limb Essential Tremor
Upper Limb Essential Tremor
Recruiting
Deep Brain Stimulation Surgery for Movement Disorders
Parkinson's Disease, Essential Tremor
RecruitingObservational study
Phenotype/Genotype Correlations in Movement Disorders
Movement Disorder
RecruitingObservational study
Analysis of Cutaneous Phosphorylated Alpha-Synuclein to Identify Patients at Risk of Progressing From Essential Tremor to Parkinson's Disease
Essential Tremor, Movement Disorders, Essential Tremor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
27 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SAGE-324 in people with Essential Tremor, run by Sage Therapeutics at 27 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score on Day 29 (time frame: Baseline, Day 29). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.