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

NCT04305275 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 324-ETD-201
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 27

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 (UL) tremor reduction in individuals with essential tremor (ET).

Conditions

Essential Tremor

Keywords

Essential Tremor; SAGE-324

Outcome Measures

Primary Outcomes (1)

• 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 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

  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

  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

  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

  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)

  From the first dose of the study drug up to the end of the study (i.e., up to approximately 42 days)

Study Arms (2)

SAGE-324 60 mg

EXPERIMENTAL

Participants received SAGE-324, 60 milligrams (mg), oral tablets, once daily (QD), in the morning for 28 days.

Drug: SAGE-324

SAGE-324 Matched Placebo

PLACEBO COMPARATOR

Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days.

Drug: SAGE-324 Placebo

Interventions

SAGE-324 DRUG

SAGE-324 oral tablet

SAGE-324 60 mg

SAGE-324 Placebo DRUG

SAGE-324 matched placebo oral tablet

SAGE-324 Matched Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sage Therapeutics: lead

Study Sites (27)

Sage Investigational Site

Phoenix, Arizona, 85258, United States

Location

Sage Investigational Site

Rogers, Arkansas, 72758, United States

Location

Sage Investigational Site

Fresno, California, 93710, United States

Location

Sage Investigational Site

Long Beach, California, 90806, United States

Location

Sage Investigational Site

Englewood, Colorado, 80113, United States

Location

Sage Investigational Site

Boca Raton, Florida, 33486, United States

Location

Sage Investigational Site

Gainesville, Florida, 32608, United States

Location

Sage Investigational Site

Hollywood, Florida, 33024, United States

Location

Sage Investigational Site

Miami, Florida, 33136, United States

Location

Sage Investigational Site

Miami, Florida, 33176, United States

Location

Sage Investigational Site

Port Charlotte, Florida, 33980, United States

Location

Sage Investigational Site

St. Petersburg, Florida, 33713, United States

Location

Sage Investigational Site

Tampa, Florida, 33609, United States

Location

Sage Investigational Site

Decatur, Georgia, 30030, United States

Location

Sage Investigational Site

Savannah, Georgia, 31406, United States

Location

Sage Investigational Site

Springfield, Illinois, 62702, United States

Location

Sage Investigational Site

Kansas City, Kansas, 66160, United States

Location

Sage Investigational Site

Farmington Hills, Michigan, 48334, United States

Location

Sage Investigational Site

New York, New York, 10032, United States

Location

Sage Investigational Site

Asheville, North Carolina, 28806, United States

Location

Sage Investigational Site

Cincinnati, Ohio, 45212, United States

Location

Sage Investigational Site

Dayton, Ohio, 45417, United States

Location

Sage Investigational Site

Tulsa, Oklahoma, 74136, United States

Location

Sage Investigational Site

Houston, Texas, 77030, United States

Location

Sage Investigational Site

Richmond, Virginia, 23229, United States

Location

Sage Investigational Site

Spokane, Washington, 99202, United States

Location

Sage Investigational Site

Huntington, West Virginia, 25701, United States

Location

MeSH Terms

Conditions

Essential Tremor

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Medical Monitor
• Organization: Sage Therapeutics

info@sagerx.com

(617) 299-8380

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2020
• First Posted: March 12, 2020
• Study Start: May 19, 2020
• Primary Completion: February 1, 2021
• Study Completion: February 15, 2021
• Last Updated: April 17, 2024
• Results First Posted: April 17, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (27)