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

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).

Study Overview

• Status: Completed
• Conditions: Essential Tremor
• Intervention / Treatment: Drug: SAGE-324; Drug: SAGE-324 Placebo

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85258
      • Sage Investigational Site
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Sage Investigational Site
  • California
    • Fresno, California, United States, 93710
      • Sage Investigational Site
    • Long Beach, California, United States, 90806
      • Sage Investigational Site
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Sage Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Sage Investigational Site
    • Gainesville, Florida, United States, 32608
      • Sage Investigational Site
    • Hollywood, Florida, United States, 33024
      • Sage Investigational Site
    • Miami, Florida, United States, 33136
      • Sage Investigational Site
    • Miami, Florida, United States, 33176
      • Sage Investigational Site
    • Port Charlotte, Florida, United States, 33980
      • Sage Investigational Site
    • Saint Petersburg, Florida, United States, 33713
      • Sage Investigational Site
    • Tampa, Florida, United States, 33609
      • Sage Investigational Site
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Sage Investigational Site
    • Savannah, Georgia, United States, 31406
      • Sage Investigational Site
  • Illinois
    • Springfield, Illinois, United States, 62702
      • Sage Investigational Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Sage Investigational Site
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Sage Investigational Site
  • New York
    • New York, New York, United States, 10032
      • Sage Investigational Site
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Sage Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Sage Investigational Site
    • Dayton, Ohio, United States, 45417
      • Sage Investigational Site
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Sage Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • Sage Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23229
      • Sage Investigational Site
  • Washington
    • Spokane, Washington, United States, 99202
      • Sage Investigational Site
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Sage Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 (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.

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, 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAGE-324 60 mg; Participants received SAGE-324, 60 milligrams (mg), oral tablets, once daily (QD), in the morning for 28 days.	Drug: SAGE-324; SAGE-324 oral tablet
Placebo Comparator: SAGE-324 Matched Placebo; Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days.	Drug: SAGE-324 Placebo; SAGE-324 matched placebo oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	From the first dose of the study drug up to the end of the study (i.e., up to approximately 42 days)

Collaborators and Investigators

• Sponsor: Sage Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2020
• Primary Completion (Actual): February 1, 2021
• Study Completion (Actual): February 15, 2021

Study Registration Dates

• First Submitted: March 10, 2020
• First Submitted That Met QC Criteria: March 10, 2020
• First Posted (Actual): March 12, 2020

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Essential Tremor; SAGE-324
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Tremor; Essential Tremor
• Other Study ID Numbers: 324-ETD-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.

Drug and device information, study documents

• 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