Clinical trial NCT04305275: A Study to Evaluate the Efficacy, Safety, and Tolerability of SAGE-324 in Participants With Essential Tremor
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Essential Tremor
Keywords: Essential Tremor
SAGE-324
Lead sponsor: Sage Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-03-12
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score on Day 29
timeFrame: Baseline, Day 29
Secondary outcomes:
measure: Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42
timeFrame: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, and 42
measure: Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42
timeFrame: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, 29, and 42
measure: Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42
timeFrame: Baseline, Days 8, 15, 22, 29, and 42
measure: Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42
timeFrame: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, 29, and 42
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From the first dose of the study drug up to the end of the study (i.e., up to approximately 42 days)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Sage Investigational Site
state: Arizona
city: Rogers
country: United States
facility: Sage Investigational Site
state: Arkansas
city: Fresno
country: United States
facility: Sage Investigational Site
state: California
city: Long Beach
country: United States
facility: Sage Investigational Site
state: California
city: Englewood
country: United States
facility: Sage Investigational Site
state: Colorado
city: Boca Raton
country: United States
facility: Sage Investigational Site
state: Florida
city: Gainesville
country: United States
facility: Sage Investigational Site
state: Florida
city: Hollywood
country: United States
facility: Sage Investigational Site
state: Florida
city: Miami
country: United States
facility: Sage Investigational Site
state: Florida
city: Miami
country: United States
facility: Sage Investigational Site
state: Florida
city: Port Charlotte
country: United States
facility: Sage Investigational Site
state: Florida
city: Saint Petersburg
country: United States
facility: Sage Investigational Site
state: Florida
city: Tampa
country: United States
facility: Sage Investigational Site
state: Florida
city: Decatur
country: United States
facility: Sage Investigational Site
state: Georgia
city: Savannah
country: United States
facility: Sage Investigational Site
state: Georgia
city: Springfield
country: United States
facility: Sage Investigational Site
state: Illinois
city: Kansas City
country: United States
facility: Sage Investigational Site
state: Kansas
city: Farmington Hills
country: United States
facility: Sage Investigational Site
state: Michigan
city: New York
country: United States
facility: Sage Investigational Site
state: New York
city: Asheville
country: United States
facility: Sage Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Sage Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Sage Investigational Site
state: Ohio
city: Tulsa
country: United States
facility: Sage Investigational Site
state: Oklahoma
city: Houston
country: United States
facility: Sage Investigational Site
state: Texas
city: Richmond
country: United States
facility: Sage Investigational Site
state: Virginia
city: Spokane
country: United States
facility: Sage Investigational Site
state: Washington
city: Huntington
country: United States
facility: Sage Investigational Site
state: West Virginia
Study officials:
References: