We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04305275
Recruitment Status : Completed
First Posted : March 12, 2020
Last Update Posted : February 2, 2022
Sponsor:
Information provided by (Responsible Party):
Sage Therapeutics

Tracking Information
First Submitted Date  ICMJE March 10, 2020
First Posted Date  ICMJE March 12, 2020
Last Update Posted Date February 2, 2022
Actual Study Start Date  ICMJE June 15, 2020
Actual Primary Completion Date February 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
Change From Baseline Compared to Placebo in The Essential Tremor Rating Assessment (TETRAS) Performance Subscale Part 4 Upper Limb Tremor Score on Day 29 [ Time Frame: Baseline, Day 29 ]
TETRAS is a validated, comprehensive clinical assessment of essential tremor. For the performance subscale part 4 upper limb (UL) tremor score, all 3 maneuvers in the UL assessments of part 4 (subscale 4a, 4b, and 4c) will be completed for both arms, first for the left arm and then for the right. The part 4 subscale ordinally rates postural (limbs extended forward and wing-beating [elbows flexed]), and kinetic (finger-nose-finger maneuver) tremor on a 0 to 4 severity scale in 0.5-point increments. TETRAS Part 4 score for each upper limb ranges from 0 to 12 and for both upper limbs from 0 to 24.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
  • Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at all Other Timepoints [ Time Frame: Baseline, Day 1, 8, 15, 22 and on Day 42 (or Early Termination Visit [ETV] / End of Study [EOS]) ]
    For the performance subscale part 4 upper limb (UL) tremor score, all 3 maneuvers in the UL assessments of part 4 (subscale 4a, 4b, and 4c) will be completed for both arms, first for the left arm and then for the right. The part 4 subscale ordinally rates postural (limbs extended forward and wing-beating [elbows flexed]), and kinetic (finger-nose-finger maneuver) tremor on a 0 to 4 severity scale in 0.5-point increments. TETRAS Part 4 score for each upper limb ranges from 0 to 12 and for both upper limbs from 0 to 24.
  • Change From Baseline Compared to Placebo in Kinesia ONE Accelerometer Scores [ Time Frame: Baseline, Day 1, 8, 15, 22, 29 and on Day 42 (or ETV / EOS) ]
    Kinesia ONE is a wireless motion sensor worn distally on the index finger, which utilizes 3 orthogonal accelerometers and 3 orthogonal gyroscopes to monitor three-dimensional motion. Via the Kinesia ONE software application, measures of three-dimensional motion are converted to scores ranging from 0 to 4. Higher scores indicate greater tremor severity. Motion in each arm will be captured separately.
  • Change From Baseline Compared to Placebo in TETRAS Scale Activities of Daily Living (ADL) Score [ Time Frame: Baseline, Day 1, 8, 15, 22, 29 and on Day 42 (or ETV / EOS) ]
    The ADL subscale will assess how ET impacts typical activities of daily living (speech, eating, drinking, dressing, personal hygiene, writing, occupational impairment, social impact and activities affected by upper limb (UL) tremor). It consists of 12 items, each rated from 0 (normal activity) to 4 (severe abnormality) with overall ADL score range of 0 to 48.
  • Change From Baseline Compared to Placebo in TETRAS Total Performance Score [ Time Frame: Baseline, Day 1, 8, 15, 22, 29 and on Day 42 (or ETV / EOS) ]
    The total performance score is based on overall rating of tremor amplitude in the voice, limbs, head, face, 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.
  • Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to Day 42 ]
    A TEAE is defined as an AE with onset after the start of investigational product (IP), or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Efficacy, Safety, and Tolerability of SAGE-324 in Participants With Essential Tremor
Official Title  ICMJE 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
Brief 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 tremor reduction in individuals with essential tremor (ET).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Essential Tremor
Intervention  ICMJE
  • Drug: SAGE-324
    SAGE-324 oral tablet
  • Drug: SAGE-324 Placebo
    SAGE-324 matched placebo oral tablet
Study Arms  ICMJE
  • Experimental: SAGE-324 60 mg
    Participants will receive SAGE-324 60 mg dose (tablets) orally in the morning for 28 days.
    Intervention: Drug: SAGE-324
  • Placebo Comparator: SAGE-324 Matched Placebo
    Participants will receive SAGE-324 matched placebo, oral tablets for 28 days.
    Intervention: Drug: SAGE-324 Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 3, 2021)
69
Original Estimated Enrollment  ICMJE
 (submitted: March 10, 2020)
60
Actual Study Completion Date  ICMJE February 15, 2021
Actual Primary Completion Date February 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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 (eg, 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 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 predose 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 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.

Exclusion Criteria:

  • 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, eg, 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.
  • 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 OATP1B1 transporter.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04305275
Other Study ID Numbers  ICMJE 324-ETD-201
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.
Current Responsible Party Sage Therapeutics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Sage Therapeutics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Sage Therapeutics
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP