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A Study to Evaluate SAGE-217 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: NCT02978781
Recruitment Status : Completed
First Posted : December 1, 2016
Results First Posted : February 17, 2021
Last Update Posted : February 17, 2021
Sponsor:
Information provided by (Responsible Party):
Sage Therapeutics

Brief Summary:
This study is a three-part, multicenter, Phase 2a study to evaluate the efficacy, safety, tolerability, and pharmacokinetics of SAGE-217 in adult participants with essential tremor.

Condition or disease Intervention/treatment Phase
Essential Tremor Drug: SAGE-217 Drug: Placebo Phase 2

Detailed Description:

Part A of the study was an open-label design with morning dosing of SAGE-217 for 7 days and included 16 participants, 8 of whom qualified for, and entered, Part B.

Part B had a double-blind, placebo-controlled, randomized withdrawal design with morning dosing for 7 days.

Part C was an open-label design with morning and evening dosing for 14 days and included a different set of 18 participants.

Parts A and B were stopped early (in advance of the planned sample size).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2a, Double-Blind, Placebo-Controlled, Randomized Withdrawal Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of SAGE-217 in the Treatment of Subjects With Essential Tremor
Actual Study Start Date : March 24, 2017
Actual Primary Completion Date : November 22, 2017
Actual Study Completion Date : December 5, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tremor

Arm Intervention/treatment
Experimental: Part A: SAGE-217 Oral Solution
Participants received SAGE-217 10 mg oral solution on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7 with food in the morning.
Drug: SAGE-217
SAGE-217 Oral Solution

Experimental: Part A: SAGE-217 Capsules
Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7, orally, with food in the morning.
Drug: SAGE-217
SAGE-217 Capsules

Placebo Comparator: Part B: Placebo
Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning.
Drug: Placebo
SAGE-217 matching placebo capsules

Experimental: Part B: SAGE-217 Capsules
Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 for 7 days beginning on Day 8 with food in the morning.
Drug: SAGE-217
SAGE-217 Capsules

Experimental: Part C: SAGE-217 Capsules
Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2, 30 mg on Day 3, orally, with food in the evening. Beginning on Day 4 through Day 14, participants received a 40-mg total daily dose (administered as 10 mg with food in the morning and 30 mg with food in the evening).
Drug: SAGE-217
SAGE-217 Capsules




Primary Outcome Measures :
  1. Part A: Change From Baseline in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 7 [ Time Frame: Baseline (Day 1) and Day 7 (8 hours postdose) ]
    The accelerometer-based Kinesia kinetic tremor combined score is the sum of Kinesia kinetic tremor scores across both sides of the body. Tremor is measured using a motion sensor that transmits raw data to a computer where it converts the tremor amplitude to a Kinesia score of 0 to 4 based on validated algorithms; the total score ranges from 0 to 8, higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.

  2. Part B: Change From Randomization in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 14 [ Time Frame: Randomization (Day 8, predose) and Day 14 (predose) ]
    The accelerometer-based Kinesia kinetic tremor combined score is the sum of Kinesia kinetic tremor scores across both sides of the body. Tremor is measured using a motion sensor that transmits raw data to a computer where it converts the tremor amplitude to a Kinesia score of 0 to 4 based on validated algorithms; the total score ranges from 0 to 8, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement.

  3. Part C: Change From Baseline in the Accelerometer-based Kinesia Upper Limb Tremor Combined Score at Day 15 [ Time Frame: Baseline (Day 1) and Day 15 ]
    The accelerometer-based Kinesia upper limb total score is the sum of the individual item scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral "wing beating" postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement.


Secondary Outcome Measures :
  1. Part A: Change From Baseline in Kinesia Upper Limb Total Score at Day 7 [ Time Frame: Baseline (Day 1) and Day 7 (8 hours postdose) ]
    The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral "wing beating" postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement.

  2. Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7 [ Time Frame: Baseline (Day 1) and Day 7 (8 hours [hr] postdose [pd]) ]
    The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral "wing beating" postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4, with higher scores indicating more tremors/greater tremor amplitude. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement.

  3. Part A: Change From Baseline in the Tremor Research Group (TRG) Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Total Score at Day 7 [ Time Frame: Baseline (Day 1) and Day 7 (8 hours postdose) ]
    The TETRAS performance subscale upper limb total score is the sum of the TETRAS individual item scores from both sides of the body. The TETRAS individual item score included TETRAS Performance Subscale item 4a, 4b and 4c scores [4a: forward outstretched postural tremor (FOPT) and 4b: lateral "wing beating" postural tremor (LWBPT) scores and 4c: Kinetic tremor (KT) score] from both sides of the body. Each individual item score ranges from 0 to 4; The total upper limb score ranges from 0 to 24, higher scores indicate more severe tremor. A negative change indicates improvement.

  4. Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 [ Time Frame: Baseline (Day 1) and Day 7 (8 hours postdose) ]
    The TETRAS individual item score is the sum of the TETRAS Performance Subscale items 4a, 4b, or 4c scores [4a: forward outstretched postural tremor (FOPT), 4b: lateral "wing beating" postural tremor (LWBPT), 4c: kinetic tremor] from both sides of the body. Each TETRAS score ranges from 0 to 4; the total score ranges from 0 to 16; higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.

  5. Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 [ Time Frame: Baseline (Day 1) and Day 7 (predose) ]
    The TETRAS Performance Subscale score includes 9 items. Out of these 9 items, Item 6 is Archimedes spirals (AS), Item 7 is Handwriting, and Item 8 is Dot approximation task (DAT). Each item was scored from 0 to 4, for both sides of the body, each item has a total score of 0 to 8, where higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.

  6. Part B: Change From Randomization in the Kinesia Upper Limb Total Score at Day 14 [ Time Frame: Randomization (Day 8, predose) and Day 14 (predose) ]
    The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral "wing beating" postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Randomization indicates improvement.

  7. Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 [ Time Frame: Randomization (Day 8, predose) and Day 14 (predose) ]
    The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral "wing beating" postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Randomization indicates improvement.

  8. Part B: Change From Randomization in the TETRAS Upper Limb Total Score at Day 14 [ Time Frame: Randomization (Day 8, predose) and Day 14 (predose) ]
    The TETRAS performance subscale upper limb total score is the sum of the TETRAS individual item scores from both sides of the body. The TETRAS individual item score included TETRAS Performance Subscale item 4a, 4b and 4c scores [4a: forward outstretched postural tremor (FOPT) and 4b: lateral "wing beating" postural tremor (LWBPT) scores and 4c: Kinetic tremor (KT) score] from both sides of the body. Each individual item score ranges from 0 to 4; The total upper limb score ranges from 0 to 24, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement.

  9. Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 [ Time Frame: Randomization (Day 8, predose) and Day 14 (predose) ]
    The TETRAS individual item score is the sum of the TETRAS Performance Subscale item 4a and 4b scores [4a: forward outstretched postural tremor (FOPT) and 4b: lateral "wing beating" postural tremor (LWBPT) scores] from both sides of the body. Each TETRAS score ranges from 0 to 4; the total score ranges from 0 to 16, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement.

  10. Part B: Change From Randomization in the TETRAS Performance Subscale Item 4c (Kinetic Tremor) Combined Score at Day 14 [ Time Frame: Randomization (Day 8, predose) and Day 14 (predose) ]
    The TETRAS kinetic tremor combined score is the sum of the TETRAS Performance Subscale item 4c (kinetic tremor) scores from both sides of the body. The TETRAS kinetic tremor score ranges from 0 to 4, the total score for both sides of the body ranges from 0 to 8, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement.

  11. Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 [ Time Frame: Baseline (Day 1) and Day 14 (predose) ]
    The TETRAS Performance Subscale score includes 9 items. Out of these 9 items, Item 6 is Archimedes spirals (AS), Item 7 is Handwriting, and Item 8 is Dot approximation task (DAT). Each item was scored from 0 to 4, for both sides of the body, each item has a total score of 0 to 8, where higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.

  12. Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 [ Time Frame: Baseline (Day 1) and Day 15 ]
    The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral "wing beating" postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement.

  13. Part C: Change From Baseline in the TETRAS Upper Limb Total Score at Day 15 [ Time Frame: Baseline (Day 1) and Day 15 ]
    The TETRAS performance subscale upper limb total score is the sum of the TETRAS individual item scores from both sides of the body. Each individual item score ranges from 0 to 4; The total upper limb score ranges from 0 to 24, higher scores indicate more severe tremor. A negative change indicates improvement.

  14. Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 [ Time Frame: Baseline (Day 1) and Day 15 ]
    The TETRAS individual item score is the sum of the TETRAS Performance Subscale item 4a and 4b scores [4a: forward outstretched postural tremor (FOPT) and 4b: lateral "wing beating" postural tremor (LWBPT) scores] from both sides of the body. Each TETRAS score ranges from 0 to 4; the total score ranges from 0 to 16, higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.

  15. Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 [ Time Frame: Baseline (Day 1) and Day 15 ]
    The TETRAS Performance Subscale score includes 9 items. Out of these 9 items, Item 6 is Archimedes spirals (AS), Item 7 is Handwriting, and Item 8 is Dot approximation task (DAT). Each item was scored from 0 to 4, for both sides of the body, each item has a total score of 0 to 8, where higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.

  16. Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) [ Time Frame: From first dose of study drug through 14 days after the last dose (Up to 28 days) ]
    An Adverse Event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. Adverse events that occurred after the first administration of study drug were denoted as TEAEs. A Serious Adverse Event (SAE) was an AE occurring during any study phase and at any dose of the study drug, comparator, or placebo, that fulfilled the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

  17. Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Baseline and post-baseline (up to 28 days) ]
    The C-SSRS consists of a baseline and post-baseline (PB) evaluation that assesses the lifetime experience of the participants with suicidal ideation and behavior. The data for suicidal ideation were summarized for participants who answered 'Yes'. Suicide ideation was categorized as 1) wish to be dead and 2) non-specific active suicidal thoughts.

  18. Number of Participants With Clinically Significant Vital Signs [ Time Frame: Up to 28 days ]
    Vital signs included heart rate, respiratory rate, temperature, and blood pressure.

  19. Number of Participants With Clinically Significant Laboratory Parameters [ Time Frame: Up to 28 days ]
    Laboratory parameters included hematology, blood chemistry, and urinalysis.

  20. Number of Participants With Clinically Significant Electrocardiogram (ECG) Values [ Time Frame: Up to 28 days ]
    A 12-lead ECG was performed.

  21. Parts A and B: Change From Baseline in Stanford Sleepiness Scale (SSS) [ Time Frame: Baseline (Day 1), Day 7 (predose) for Part A, Day 14 (predose) for Part B ]
    The SSS was designed to quickly assess how alert a subject is feeling. Degrees of sleepiness and alertness are rated on a scale of 1 to 7, where the lowest score of 1 indicates the subject is "feeling active, vital, alert, or wide awake" and the highest score of 7 indicates the participant is "no longer fighting sleep, sleep onset soon; having dream-like thoughts". Greater changes from baseline indicate greater sedation. A positive change from baseline indicates improvement.

  22. Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score [ Time Frame: Baseline (Day 1), Day 7 (predose) for Part A, Day 14 (predose) for Part B and Day 15 for Part C ]

    Mood was assessed using the Bond-Lader VAS score. This is a 16-part self-administered questionnaire that employs a 100-mm VAS to explore different aspects of self-reported mood. Three factor scores for (alertness, contentedness, and calmness) were calculated using following equations based on normalized VAS scores:

    • Alertness = 0.827X1 + 0.618X3 + 0.755X4 + 0.642X5 + 0.776X6 + 0.635X9 + 0.792X11 + 0.593X12 + 0.614X15;
    • Contentedness = 0.677X7 + 0.697X8 + 0.823X13 + 0.738X14 + 0.594X16; and
    • Calmness = 0.845X2 + 0.677X10,

    where Xi represents a subject's item score after normalization, and i represents the item number from the entire scale (in order from 1-16). A negative change from baseline (CFB) indicated more alertness, more contentedness, and more calmness.


  23. Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score [ Time Frame: Baseline (Day 1), Day 7 (2 hours postdose) for Part A, Day 14 (2 hours postdose) for Part B and Day 15 for Part C ]
    Participants responded to 5 DEQs based on how they are feeling after taking the study drug. DEQ-5 were as follows; Q1: Do you FEEL a drug effect right now? Q2: Are you HIGH right now? Q3: Do you DISLIKE any of the effects that you are feeling right now? Q4: Do you LIKE any of the effects that you are feeling right now? Q5: Would you like MORE of the drug you took, right now? The answers were recorded on a 100-mm VAS, with the answer for each being "Not at all" (0 mm) and "Extremely" (100 mm) at the extremes. There were options to record "Not applicable" for questions 3 and 4 if no drug effects were felt and for question 5 prior to administration of study medication, and these participants were excluded from the data summarization. Higher score on Q1 indicates a drug effect; on Q2 indicates feeling high; on Q3 indicates disliking the drug; and on Q4 and Q5 indicates liking the drug.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Participant must have a diagnosis of Essential Tremor (ET), defined as bilateral postural tremor and kinetic tremor, involving hands and forearms, that is visible and persistent and the duration is >5 years prior to screening.

Key Exclusion Criteria:

  • Participant has presence of abnormal neurological signs other than tremor or Froment's sign.
  • Participant has presence of known causes of enhanced physiological tremor.
  • Participant has concurrent or recent exposure (14 days prior to admission visit) to tremorogenic drugs.
  • Participant has had direct or indirect trauma to the nervous system within 3 months before the onset of tremor.
  • Participant has historical or clinical evidence of tremor with psychogenic origin.
  • Participant has convincing evidence of sudden tremor onset or evidence of stepwise deterioration of tremor.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02978781


Locations
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United States, Alabama
Sage Investigational Site
Anniston, Alabama, United States, 36207
United States, Arkansas
Sage Investigational Site
Little Rock, Arkansas, United States, 72211
Sage Investigational Site
Rogers, Arkansas, United States, 72758
United States, California
Sage Investigational Site
Cerritos, California, United States, 90703
Sage Investigational Site
Fountain Valley, California, United States, 92708
Sage Investigational Site
Oceanside, California, United States, 92056
Sage Investigational Site
San Diego, California, United States, 92103
United States, Colorado
Sage Investigational Site
Englewood, Colorado, United States, 80113
United States, Florida
Sage Investigational Site
Clearwater, Florida, United States, 33756
Sage Investigational Site
DeLand, Florida, United States, 32720
Sage Investigational Site
Lauderdale Lakes, Florida, United States, 33319
Sage Investigational Site
Orlando, Florida, United States, 32806
Sage Investigational Site
Ormond Beach, Florida, United States, 32174
Sage Investigational Site
Saint Petersburg, Florida, United States, 33713
Sage Investigational Site
Tampa, Florida, United States, 33612
United States, Georgia
Sage Investigational Site
Atlanta, Georgia, United States, 30331
Sage Investigational Site
Decatur, Georgia, United States, 30030
United States, Illinois
Sage Investigational Site
Chicago, Illinois, United States, 60612
Sage Investigational Site
Urbana, Illinois, United States, 61801
United States, Missouri
Sage Investigational Site
Saint Louis, Missouri, United States, 63141
Sage Investigational Site
Springfield, Missouri, United States, 65802
United States, North Carolina
Sage Investigational Site
Raleigh, North Carolina, United States, 27612
United States, Ohio
Sage Investigational Site
Cincinnati, Ohio, United States, 45212
Sage Investigational Site
Dayton, Ohio, United States, 45417
United States, Tennessee
Sage Investigational Site
Nashville, Tennessee, United States, 37232
United States, Texas
Sage Investigational Site
Fort Worth, Texas, United States, 76104
Sponsors and Collaborators
Sage Therapeutics
Investigators
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Study Director: Christopher Silber, MD Sage Therapeutics
  Study Documents (Full-Text)

Documents provided by Sage Therapeutics:
Statistical Analysis Plan  [PDF] December 14, 2017
Study Protocol  [PDF] September 5, 2017

Additional Information:
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Responsible Party: Sage Therapeutics
ClinicalTrials.gov Identifier: NCT02978781    
Other Study ID Numbers: 217-ETD-201
First Posted: December 1, 2016    Key Record Dates
Results First Posted: February 17, 2021
Last Update Posted: February 17, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sage Therapeutics:
Tremor
Additional relevant MeSH terms:
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Tremor
Essential Tremor
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Movement Disorders
Central Nervous System Diseases