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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
69
SAGE-324 oral tablet
SAGE-324 matched placebo oral tablet
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.
Time frame: Baseline, Day 29
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.
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
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Sage Investigational Site
Phoenix, Arizona, United States
Sage Investigational Site
Rogers, Arkansas, United States
Sage Investigational Site
Fresno, California, United States
Sage Investigational Site
Long Beach, California, United States
Sage Investigational Site
Englewood, Colorado, United States
Sage Investigational Site
Boca Raton, Florida, United States
Sage Investigational Site
Gainesville, Florida, United States
Sage Investigational Site
Hollywood, Florida, United States
Sage Investigational Site
Miami, Florida, United States
Sage Investigational Site
Miami, Florida, United States
...and 17 more locations
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.
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
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.
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
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.
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)
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.
Time frame: From the first dose of the study drug up to the end of the study (i.e., up to approximately 42 days)