ARTISTS2: A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)

Sponsor
Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03571256
Collaborator
Nuvelution TS Pharma, Inc. (Industry)
158
56
3
18.3
2.8
0.2

Study Details

Study Description

Brief Summary

Standard placebo-controlled, double-blind study design (TEV-50717 [low dose and high dose] vs. placebo in a 1:1:1 ratio) was chosen to determine whether study drug treatment results in a statistically significant effect on the tics in participants with TS.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
158 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Well-Controlled, Fixed-Dose Study of TEV-50717 (Deutetrabenazine) for the Treatment of Tics Associated With Tourette Syndrome
Actual Study Start Date :
May 31, 2018
Actual Primary Completion Date :
Dec 9, 2019
Actual Study Completion Date :
Dec 9, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: TEV-50717 High-Dose

TEV-50717 tablets twice daily (BID) up to 48 milligrams (mg)/day orally for a total of 8 weeks

Drug: TEV-50717
6-, 9-, 12-, 15-, and 18 mg oral tablets
Other Names:
  • AUSTEDO, Deutetrabenazine
  • Drug: Placebo
    Placebo matched to TEV-50717 tablets will be taken BID.

    Experimental: TEV-50717 Low-Dose

    TEV-50717 tablets BID up to 36 mg/day orally for a total of 8 weeks

    Drug: TEV-50717
    6-, 9-, 12-, 15-, and 18 mg oral tablets
    Other Names:
  • AUSTEDO, Deutetrabenazine
  • Drug: Placebo
    Placebo matched to TEV-50717 tablets will be taken BID.

    Placebo Comparator: Placebo

    Placebo matched to TEV-50717 for a total of 8 weeks

    Drug: Placebo
    Placebo matched to TEV-50717 tablets will be taken BID.

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in the TTS of the YGTSS at Week 8 Between High-Dose TEV-50717-Treated Participants and Placebo-Treated Participants [Baseline, Week 8]

      YGTSS rating scale is a semi-structured clinician rating instrument that provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic tics. YGTSS is composed of 11 items: 5 items for motor tic severity, 5 items for vocal tic severity, and 1 item for impairment. Each item for motor tic severity and vocal is rated on a 6-point scale (0 for none to 5 to severe). MTSS is the sum of the 5 items for motor tic severity and VTSS is the sum of the 5 items for vocal tic severity. TTS is the sum of MTSS and VTSS, ranges from 0 (none/absent) to 50 (severe). Higher scores indicate greater severity/worse outcome. Least square (LS) mean and standard error (SE) was calculated using mixed-model repeated-measures (MMRM) with treatment group, week (3 levels: Weeks 2, 4, and 8), and the treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6 to 11 years, 12 to 16 years) as covariates.

    Secondary Outcome Measures

    1. Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score at Week 8 Between High-Dose TEV-50717-Treated Participants and Placebo-Treated Participants [Baseline, Week 8]

      The TS-CGI scale is a 7-point Likert scale that allows the clinician to use all available information to assess the impact of tics on the participant's quality of life. The TS-CGI is rated as follows: 1 (normal or no tics at all), 2 (borderline), 3 (mild), 4 (moderate), 5 (marked), 6 (severe), and 7 (extreme, incapacitating tics). Lower scores indicate better quality of life. LS mean and SE was calculated using MMRM with treatment group, week (3 levels: Weeks 2, 4, and 8), and the treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6 to 11 years, 12 to 16 years) as covariates.

    2. Change From Baseline in the TTS of the YGTSS at Week 8 Between Low-Dose TEV-50717-Treated Participants and Placebo-Treated Participants [Baseline, Week 8]

      YGTSS rating scale is a semi-structured clinician rating instrument that provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic tics. YGTSS is composed of 11 items: 5 items for motor tic severity, 5 items for vocal tic severity, and 1 item for impairment. Each item for motor tic severity and vocal is rated on a 6-point scale (0 for none to 5 to severe). MTSS is the sum of the 5 items for motor tic severity and VTSS is the sum of the 5 items for vocal tic severity. TTS is the sum of MTSS and VTSS, ranges from 0 (none/absent) to 50 (severe). Higher scores indicate greater severity/worse outcome. LS mean and SE was calculated using MMRM with treatment group, week (3 levels: Weeks 2, 4, and 8), and the treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6 to 11 years, 12 to 16 years) as covariates.

    3. Change From Baseline in the TS-CGI Score at Week 8 Between Low-Dose TEV-50717-Treated Participants and Placebo-Treated Participants [Baseline, Week 8]

      The TS-CGI scale is a 7-point Likert scale that allows the clinician to use all available information to assess the impact of tics on the participant's quality of life. The TS-CGI is rated as follows: 1 (normal or no tics at all), 2 (borderline), 3 (mild), 4 (moderate), 5 (marked), 6 (severe), and 7 (extreme, incapacitating tics). Lower scores indicate better quality of life. LS mean and SE was calculated using MMRM with treatment group, week (3 levels: Weeks 2, 4, and 8), and the treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6 to 11 years, 12 to 16 years) as covariates.

    4. Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score at Week 8 Between High-Dose TEV-50717-Treated Participants and Placebo-Treated Participants [Baseline, Week 8]

      The TS-PGII is a single-item questionnaire that asks the participant to assess the degree of impact due to current tics (How much do your current tics disrupt things in your life?). The TS-PGII uses a 5-point scale, ranging from not at all (1) to very much (5), to assess overall response to therapy.

    5. Change From Baseline in the TS-PGII Score at Week 8 Between Low-Dose TEV-50717-Treated Participants and Placebo-Treated Participants [Baseline, Week 8]

      The TS-PGII is a single-item questionnaire that asks the participant to assess the degree of impact due to current tics (How much do your current tics disrupt things in your life?). The TS-PGII uses a 5-point scale, ranging from not at all (1) to very much (5), to assess overall response to therapy.

    6. Change From Baseline in the Child and Adolescent Gilles de la Tourette Syndrome - Quality of Life (C&A-GTS-QOL) Activities of Daily Living (ADL) Subscale Score at Week 8 Between High-Dose TEV-50717-Treated Participants and Placebo-Treated Participants [Baseline, Week 8]

      C&A-GTS-QOL is a 27-item questionnaire that asks participant to assess the extent to which their quality of life is impacted by their symptoms. C&A-GTS-QOL contains 6 subscales (cognitive, coprophenomena, psychological, physical, obsessive-compulsive, and ADL) and uses a 5-point Likert scale ranging from no problem to extreme problem. Following 3 questions from 27-item questionnaire were assessed in ADL C&A-GTS-QOL subscale: Question 2 (Had difficulty with school or sport activities?), 24 (Felt you needed more help or support from other people?), and 26 (Had difficulty going out with other people?). Total score of ADL subscale ranged from 0 (no problem) to 12 (extreme problem). Lower score indicated better quality of life. LS mean and SE was calculated using MMRM with treatment group, week (3 levels: Weeks 2, 4, and 8), and treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6-11 years, 12-16 years) as covariates.

    7. Change From Baseline in the C&A-GTS-QOL ADL Subscale Score at Week 8 Between Low-Dose TEV-50717-Treated Participants and Placebo-Treated Participants [Baseline, Week 8]

      C&A-GTS-QOL is a 27-item questionnaire that asks participant to assess the extent to which their quality of life is impacted by their symptoms. C&A-GTS-QOL contains 6 subscales (cognitive, coprophenomena, psychological, physical, obsessive-compulsive, and ADL) and uses a 5-point Likert scale ranging from no problem to extreme problem. Following 3 questions from 27-item questionnaire were assessed in ADL C&A-GTS-QOL subscale: Question 2 (Had difficulty with school or sport activities?), 24 (Felt you needed more help or support from other people?), and 26 (Had difficulty going out with other people?). Total score of ADL subscale ranged from 0 (no problem) to 12 (extreme problem). Lower score indicated better quality of life. LS mean and SE was calculated using MMRM with treatment group, week (3 levels: Weeks 2, 4, and 8), and treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6-11 years, 12-16 years) as covariates.

    8. Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version and Self-reported Version) Total Score at Week 9 [Baseline, Week 9]

      CDI-2 self-report: 28-item questionnaire assessing depressive symptoms in children 7 to 17 years of age with basic reading and comprehension skills. Children were asked to choose 1 of 3 statements that most closely aligns with their feelings in past 2 weeks. It contains 6 subscales (emotional problem, negative mood/physical symptoms, negative self-esteem, functional problems, ineffectiveness, interpersonal problems). Total score: sum of all subscales scores, ranging from 0 to 56, with higher score indicating greater depression severity.CDI-2 parent: 17-item questionnaire administered to parents to assess depression-related behaviors observed in their children. Parents were asked to rate their child's behaviors in past 2 weeks on a 4-point Likert scale from "not at all" to "much or most of the time." It contains 2 subscales (emotional problems and functional problem). Total score: sum of 2 subscales, ranging from 0 to 51, with higher score indicating more depression-related behaviors.

    9. Number of Participants at Baseline and Week 9 With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) [Baseline, Week 9]

      C-SSRS included responses for Suicidal Ideation or Suicidal Behavior in following 10 categories: 1 = Wish to be dead; 2 = Non-specific active suicidal thoughts; 3 = Active suicidal ideation with any methods (not plan) without intent to act; 4 = Active suicidal ideation with some intent to act, without specific plan; 5 = Active suicidal ideation with specific plan and intent; 6 = Preparatory acts or behavior; 7 = Aborted attempt; 8 = Interrupted attempt; 9 = Non-fatal suicide attempt; and 10 = Completed suicide. Number of participants with any suicidal ideation or suicidal behavior are reported. Any Suicidal ideation or Suicidal Behavior events reported as TEAEs along with all other reported TEAEs are included in the AE module.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Years to 16 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Participant weighs at least 44 pounds (20 kg) at baseline.

    • Participant meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5™) diagnostic criteria for TS and, in the opinion of the investigator, participant, and parent/legal guardian, the participant's active tics are causing distress or impairment.

    • Participant has a TTS of 20 or higher on the YGTSS at screening and baseline.

    • Participant is able to swallow study medication whole.

    • -Additional criteria apply, please contact the investigator for more information

    Exclusion Criteria:
    • Participant has a neurologic disorder other than TS that could obscure the evaluation of tics.

    • The participant 's predominant movement disorder is stereotypy (coordinated movements that repeat continually and identically) associated with autism spectrum disorder.

    • Participant has clinically significant depression at screening or baseline.

    • Participant has a history of suicidal intent or related behaviors within 2 years of screening

    • Participant has a history of a previous actual, interrupted, or aborted suicide attempt.

    • Participant has a first-degree relative who has completed suicide.

    • Participant has a confirmed diagnosis of bipolar disorder, schizophrenia, or another psychotic disorder.

    • Participant has received Comprehensive Behavioral Intervention for Tics for TS or Cognitive Behavioral Therapy for obsessive-compulsive disorder (OCD) within 4 weeks of screening.

    • Participant has received treatment with deep brain stimulation, transmagnetic stimulation, or transcranial direct current stimulation within 4 weeks of the screening visit for reduction of tics.

    • Participant has a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure.

    • Participant has participated in an investigational drug or device study and received investigational medicinal product (IMP)/intervention within 30 days or 5 drug half-lives of baseline, whichever is longer.

    • Participant is a pregnant or lactating female, or plans to be pregnant during the study.

    • -Additional criteria apply, please contact the investigator for more information

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Teva Investigational Site 060-0160 Gainesville Florida United States 32608
    2 Teva Investigational Site 060-0166 Gulf Breeze Florida United States 32561-4458
    3 Teva Investigational Site 060-0161 Miami Florida United States 33136-2107
    4 Teva Investigational Site 060-0151 Orlando Florida United States 32801
    5 Teva Investigational Site 060-0153 Orlando Florida United States 32819
    6 Teva Investigational Site 060-0168 Atlanta Georgia United States 30329
    7 Teva Investigational Site 060-0155 Chicago Illinois United States 60612
    8 Teva Investigational Site 060-0164 Chicago Illinois United States 60634
    9 Teva Investigational Site 060-0152 Indianapolis Indiana United States 46256
    10 Teva Investigational Site 060-0158 Louisville Kentucky United States 40202
    11 Teva Investigational Site 060-0167 Rockville Maryland United States 20852-4219
    12 Teva Investigational Site 060-0165 Ann Arbor Michigan United States 48105
    13 Teva Investigational Site 060-0170 Bridgeton Missouri United States 63044
    14 Teva Investigational Site 060-0154 New York New York United States 10036
    15 Teva Investigational Site 060-0169 Charleston South Carolina United States 29414-5834
    16 Teva Investigational Site 060-0157 Memphis Tennessee United States 38157
    17 Teva Investigational Site 060-0156 Nashville Tennessee United States 37232-2551
    18 Teva Investigational Site 060-0163 Fort Worth Texas United States 76104
    19 Teva Investigational Site 060-0162 Everett Washington United States 98201-4077
    20 Teva Investigational Site 060-1407 Buenos Aires Argentina C1023AAB
    21 Teva Investigational Site 060-1401 Buenos Aires Argentina C1058AAJ
    22 Teva Investigational Site 060-1402 Buenos Aires Argentina C1425AHQ
    23 Teva Investigational Site 060-1403 La Plata Argentina 1900
    24 Teva Investigational Site 060-1404 Mendoza Argentina 5500
    25 Teva Investigational Site 060-1802 Liverpool Australia 2170
    26 Teva Investigational Site 060-1801 Parkville Australia 3052
    27 Teva Investigational Site 060-1503 Bello Colombia 051050
    28 Teva Investigational Site 060-1501 Medellin Colombia 5500515
    29 Teva Investigational Site 060-1506 Medellin Colombia 78 B 50
    30 Teva Investigational Site 060-1504 Pereira Colombia 660003
    31 Teva Investigational Site 060-0901 Budapest Hungary 1021
    32 Teva Investigational Site 060-0902 Szeged Hungary 6725
    33 Teva Investigational Site 060-1005 Cagliari Italy 09121
    34 Teva Investigational Site 060-1001 Catania Italy 95123
    35 Teva Investigational Site 060-1003 Naples Italy 80131
    36 Teva Investigational Site 060-1004 Rome Italy 00165
    37 Teva Investigational Site 060-1901 Seoul Korea, Republic of 110-744
    38 Teva Investigational Site 060-1903 Seoul Korea, Republic of 138-736
    39 Teva Investigational Site 060-1904 Seoul Korea, Republic of 3722
    40 Teva Investigational Site 060-1902 Seoul Korea, Republic of 6351
    41 Teva Investigational Site 060-1601 Culiacan Mexico 80020
    42 Teva Investigational Site 060-1603 Leon Mexico 37000
    43 Teva Investigational Site 060-1602 Monterrey Mexico 64460
    44 Teva Investigational Site 060-1604 Monterrey Mexico 64610
    45 Teva Investigational Site 060-1104 Gdansk Poland 80-542
    46 Teva Investigational Site 060-1101 Katowice Poland 40-123
    47 Teva Investigational Site 060-1105 Krakow Poland 31503
    48 Teva Investigational Site 060-1102 Poznan Poland 60-693
    49 Teva Investigational Site 060-1106 Torun Poland 87-100
    50 Teva Investigational Site 060-1103 Warsaw Poland 02-793
    51 Teva Investigational Site 060-2003 Dnipropetrovsk Ukraine 49101
    52 Teva Investigational Site 060-2001 Kharkiv Ukraine 61068
    53 Teva Investigational Site 060-2002 Kharkiv Ukraine 61153
    54 Teva Investigational Site 060-2007 Kiev Ukraine 4080
    55 Teva Investigational Site 060-2005 Kyiv Ukraine 4209
    56 Teva Investigational Site 060-2006 Vinnytsia Ukraine 21005

    Sponsors and Collaborators

    • Teva Branded Pharmaceutical Products R&D, Inc.
    • Nuvelution TS Pharma, Inc.

    Investigators

    • Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Teva Branded Pharmaceutical Products R&D, Inc.
    ClinicalTrials.gov Identifier:
    NCT03571256
    Other Study ID Numbers:
    • TV50717-CNS-30060
    • 2017-002976-24
    First Posted:
    Jun 27, 2018
    Last Update Posted:
    Nov 9, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail A total of 158 participants were randomized in a 1:1:1 ratio to TEV-50717 high-dose, TEV-50717 low-dose or placebo group.
    Arm/Group Title TEV-50717 High-Dose TEV-50717 Low-Dose Placebo
    Arm/Group Description TEV-50717 tablets twice daily (BID) up to 48 milligrams (mg)/day orally for a total of 8 weeks TEV-50717 tablets BID up to 36 mg/day orally for a total of 8 weeks Placebo matched to TEV-50717 for a total of 8 weeks
    Period Title: Overall Study
    STARTED 52 54 52
    Safety Analysis Set 52 54 51
    Modified ITT (mITT) Analysis Set 49 53 51
    COMPLETED 46 51 48
    NOT COMPLETED 6 3 4

    Baseline Characteristics

    Arm/Group Title TEV-50717 High-Dose TEV-50717 Low-Dose Placebo Total
    Arm/Group Description TEV-50717 tablets BID up to 48 mg/day orally for a total of 8 weeks TEV-50717 tablets BID up to 36 mg/day orally for a total of 8 weeks Placebo matched to TEV-50717 for a total of 8 weeks Total of all reporting groups
    Overall Participants 52 54 52 158
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    11.7
    (2.63)
    11.7
    (2.70)
    11.8
    (2.62)
    11.7
    (2.64)
    Sex: Female, Male (Count of Participants)
    Female
    15
    28.8%
    12
    22.2%
    12
    23.1%
    39
    24.7%
    Male
    37
    71.2%
    42
    77.8%
    40
    76.9%
    119
    75.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    8
    15.4%
    9
    16.7%
    15
    28.8%
    32
    20.3%
    Not Hispanic or Latino
    43
    82.7%
    45
    83.3%
    37
    71.2%
    125
    79.1%
    Unknown or Not Reported
    1
    1.9%
    0
    0%
    0
    0%
    1
    0.6%
    Race/Ethnicity, Customized (Count of Participants)
    White
    48
    92.3%
    48
    88.9%
    39
    75%
    135
    85.4%
    Black
    0
    0%
    1
    1.9%
    0
    0%
    1
    0.6%
    Asian
    0
    0%
    3
    5.6%
    4
    7.7%
    7
    4.4%
    Native American
    1
    1.9%
    1
    1.9%
    2
    3.8%
    4
    2.5%
    Multiple
    0
    0%
    0
    0%
    2
    3.8%
    2
    1.3%
    Other
    3
    5.8%
    1
    1.9%
    5
    9.6%
    9
    5.7%
    Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    33.9
    (6.17)
    32.9
    (7.20)
    34.7
    (6.29)
    33.8
    (6.58)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in the TTS of the YGTSS at Week 8 Between High-Dose TEV-50717-Treated Participants and Placebo-Treated Participants
    Description YGTSS rating scale is a semi-structured clinician rating instrument that provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic tics. YGTSS is composed of 11 items: 5 items for motor tic severity, 5 items for vocal tic severity, and 1 item for impairment. Each item for motor tic severity and vocal is rated on a 6-point scale (0 for none to 5 to severe). MTSS is the sum of the 5 items for motor tic severity and VTSS is the sum of the 5 items for vocal tic severity. TTS is the sum of MTSS and VTSS, ranges from 0 (none/absent) to 50 (severe). Higher scores indicate greater severity/worse outcome. Least square (LS) mean and standard error (SE) was calculated using mixed-model repeated-measures (MMRM) with treatment group, week (3 levels: Weeks 2, 4, and 8), and the treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6 to 11 years, 12 to 16 years) as covariates.
    Time Frame Baseline, Week 8

    Outcome Measure Data

    Analysis Population Description
    mITT analysis set included all randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline YGTSS assessment.
    Arm/Group Title TEV-50717 High-Dose Placebo
    Arm/Group Description TEV-50717 tablets BID up to 48 mg/day orally for a total of 8 weeks Placebo matched to TEV-50717 for a total of 8 weeks
    Measure Participants 49 51
    Least Squares Mean (Standard Error) [units on a scale]
    -7.8
    (1.24)
    -7.0
    (1.16)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TEV-50717 High-Dose, Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.600
    Comments Threshold for significance at 0.05 level.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -3.9 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score at Week 8 Between High-Dose TEV-50717-Treated Participants and Placebo-Treated Participants
    Description The TS-CGI scale is a 7-point Likert scale that allows the clinician to use all available information to assess the impact of tics on the participant's quality of life. The TS-CGI is rated as follows: 1 (normal or no tics at all), 2 (borderline), 3 (mild), 4 (moderate), 5 (marked), 6 (severe), and 7 (extreme, incapacitating tics). Lower scores indicate better quality of life. LS mean and SE was calculated using MMRM with treatment group, week (3 levels: Weeks 2, 4, and 8), and the treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6 to 11 years, 12 to 16 years) as covariates.
    Time Frame Baseline, Week 8

    Outcome Measure Data

    Analysis Population Description
    mITT analysis set included all randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline YGTSS assessment.
    Arm/Group Title TEV-50717 High-Dose Placebo
    Arm/Group Description TEV-50717 tablets BID up to 48 mg/day orally for a total of 8 weeks Placebo matched to TEV-50717 for a total of 8 weeks
    Measure Participants 49 51
    Least Squares Mean (Standard Error) [units on a scale]
    -0.8
    (0.14)
    -0.6
    (0.13)
    3. Secondary Outcome
    Title Change From Baseline in the TTS of the YGTSS at Week 8 Between Low-Dose TEV-50717-Treated Participants and Placebo-Treated Participants
    Description YGTSS rating scale is a semi-structured clinician rating instrument that provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic tics. YGTSS is composed of 11 items: 5 items for motor tic severity, 5 items for vocal tic severity, and 1 item for impairment. Each item for motor tic severity and vocal is rated on a 6-point scale (0 for none to 5 to severe). MTSS is the sum of the 5 items for motor tic severity and VTSS is the sum of the 5 items for vocal tic severity. TTS is the sum of MTSS and VTSS, ranges from 0 (none/absent) to 50 (severe). Higher scores indicate greater severity/worse outcome. LS mean and SE was calculated using MMRM with treatment group, week (3 levels: Weeks 2, 4, and 8), and the treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6 to 11 years, 12 to 16 years) as covariates.
    Time Frame Baseline, Week 8

    Outcome Measure Data

    Analysis Population Description
    mITT analysis set included all randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline YGTSS assessment.
    Arm/Group Title TEV-50717 Low-Dose Placebo
    Arm/Group Description TEV-50717 tablets BID up to 36 mg/day orally for a total of 8 weeks Placebo matched to TEV-50717 for a total of 8 weeks
    Measure Participants 53 51
    Least Squares Mean (Standard Error) [units on a scale]
    -5.9
    (1.18)
    -7.0
    (1.16)
    4. Secondary Outcome
    Title Change From Baseline in the TS-CGI Score at Week 8 Between Low-Dose TEV-50717-Treated Participants and Placebo-Treated Participants
    Description The TS-CGI scale is a 7-point Likert scale that allows the clinician to use all available information to assess the impact of tics on the participant's quality of life. The TS-CGI is rated as follows: 1 (normal or no tics at all), 2 (borderline), 3 (mild), 4 (moderate), 5 (marked), 6 (severe), and 7 (extreme, incapacitating tics). Lower scores indicate better quality of life. LS mean and SE was calculated using MMRM with treatment group, week (3 levels: Weeks 2, 4, and 8), and the treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6 to 11 years, 12 to 16 years) as covariates.
    Time Frame Baseline, Week 8

    Outcome Measure Data

    Analysis Population Description
    mITT analysis set included all randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline YGTSS assessment.
    Arm/Group Title TEV-50717 Low-Dose Placebo
    Arm/Group Description TEV-50717 tablets BID up to 36 mg/day orally for a total of 8 weeks Placebo matched to TEV-50717 for a total of 8 weeks
    Measure Participants 53 51
    Least Squares Mean (Standard Error) [units on a scale]
    -0.6
    (0.13)
    -0.6
    (0.13)
    5. Secondary Outcome
    Title Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score at Week 8 Between High-Dose TEV-50717-Treated Participants and Placebo-Treated Participants
    Description The TS-PGII is a single-item questionnaire that asks the participant to assess the degree of impact due to current tics (How much do your current tics disrupt things in your life?). The TS-PGII uses a 5-point scale, ranging from not at all (1) to very much (5), to assess overall response to therapy.
    Time Frame Baseline, Week 8

    Outcome Measure Data

    Analysis Population Description
    mITT analysis set included all randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline YGTSS assessment.
    Arm/Group Title TEV-50717 High-Dose Placebo
    Arm/Group Description TEV-50717 tablets BID up to 48 mg/day orally for a total of 8 weeks Placebo matched to TEV-50717 for a total of 8 weeks
    Measure Participants 49 51
    Mean (Standard Error) [units on a scale]
    -0.8
    (0.17)
    -0.7
    (0.16)
    6. Secondary Outcome
    Title Change From Baseline in the TS-PGII Score at Week 8 Between Low-Dose TEV-50717-Treated Participants and Placebo-Treated Participants
    Description The TS-PGII is a single-item questionnaire that asks the participant to assess the degree of impact due to current tics (How much do your current tics disrupt things in your life?). The TS-PGII uses a 5-point scale, ranging from not at all (1) to very much (5), to assess overall response to therapy.
    Time Frame Baseline, Week 8

    Outcome Measure Data

    Analysis Population Description
    mITT analysis set included all randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline YGTSS assessment.
    Arm/Group Title TEV-50717 Low-Dose Placebo
    Arm/Group Description TEV-50717 tablets BID up to 36 mg/day orally for a total of 8 weeks Placebo matched to TEV-50717 for a total of 8 weeks
    Measure Participants 53 51
    Mean (Standard Error) [units on a scale]
    -0.7
    (0.15)
    -0.7
    (0.16)
    7. Secondary Outcome
    Title Change From Baseline in the Child and Adolescent Gilles de la Tourette Syndrome - Quality of Life (C&A-GTS-QOL) Activities of Daily Living (ADL) Subscale Score at Week 8 Between High-Dose TEV-50717-Treated Participants and Placebo-Treated Participants
    Description C&A-GTS-QOL is a 27-item questionnaire that asks participant to assess the extent to which their quality of life is impacted by their symptoms. C&A-GTS-QOL contains 6 subscales (cognitive, coprophenomena, psychological, physical, obsessive-compulsive, and ADL) and uses a 5-point Likert scale ranging from no problem to extreme problem. Following 3 questions from 27-item questionnaire were assessed in ADL C&A-GTS-QOL subscale: Question 2 (Had difficulty with school or sport activities?), 24 (Felt you needed more help or support from other people?), and 26 (Had difficulty going out with other people?). Total score of ADL subscale ranged from 0 (no problem) to 12 (extreme problem). Lower score indicated better quality of life. LS mean and SE was calculated using MMRM with treatment group, week (3 levels: Weeks 2, 4, and 8), and treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6-11 years, 12-16 years) as covariates.
    Time Frame Baseline, Week 8

    Outcome Measure Data

    Analysis Population Description
    mITT analysis set included all randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline YGTSS assessment.
    Arm/Group Title TEV-50717 High-Dose Placebo
    Arm/Group Description TEV-50717 tablets BID up to 48 mg/day orally for a total of 8 weeks Placebo matched to TEV-50717 for a total of 8 weeks
    Measure Participants 49 51
    Least Squares Mean (Standard Error) [units on a scale]
    -10.3
    (2.85)
    -9.0
    (2.66)
    8. Secondary Outcome
    Title Change From Baseline in the C&A-GTS-QOL ADL Subscale Score at Week 8 Between Low-Dose TEV-50717-Treated Participants and Placebo-Treated Participants
    Description C&A-GTS-QOL is a 27-item questionnaire that asks participant to assess the extent to which their quality of life is impacted by their symptoms. C&A-GTS-QOL contains 6 subscales (cognitive, coprophenomena, psychological, physical, obsessive-compulsive, and ADL) and uses a 5-point Likert scale ranging from no problem to extreme problem. Following 3 questions from 27-item questionnaire were assessed in ADL C&A-GTS-QOL subscale: Question 2 (Had difficulty with school or sport activities?), 24 (Felt you needed more help or support from other people?), and 26 (Had difficulty going out with other people?). Total score of ADL subscale ranged from 0 (no problem) to 12 (extreme problem). Lower score indicated better quality of life. LS mean and SE was calculated using MMRM with treatment group, week (3 levels: Weeks 2, 4, and 8), and treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6-11 years, 12-16 years) as covariates.
    Time Frame Baseline, Week 8

    Outcome Measure Data

    Analysis Population Description
    mITT analysis set included all randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline YGTSS assessment.
    Arm/Group Title TEV-50717 Low-Dose Placebo
    Arm/Group Description TEV-50717 tablets BID up to 36 mg/day orally for a total of 8 weeks Placebo matched to TEV-50717 for a total of 8 weeks
    Measure Participants 53 51
    Least Squares Mean (Standard Error) [units on a scale]
    -10.0
    (2.68)
    -9.0
    (2.66)
    9. Secondary Outcome
    Title Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version and Self-reported Version) Total Score at Week 9
    Description CDI-2 self-report: 28-item questionnaire assessing depressive symptoms in children 7 to 17 years of age with basic reading and comprehension skills. Children were asked to choose 1 of 3 statements that most closely aligns with their feelings in past 2 weeks. It contains 6 subscales (emotional problem, negative mood/physical symptoms, negative self-esteem, functional problems, ineffectiveness, interpersonal problems). Total score: sum of all subscales scores, ranging from 0 to 56, with higher score indicating greater depression severity.CDI-2 parent: 17-item questionnaire administered to parents to assess depression-related behaviors observed in their children. Parents were asked to rate their child's behaviors in past 2 weeks on a 4-point Likert scale from "not at all" to "much or most of the time." It contains 2 subscales (emotional problems and functional problem). Total score: sum of 2 subscales, ranging from 0 to 51, with higher score indicating more depression-related behaviors.
    Time Frame Baseline, Week 9

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for specified categories.
    Arm/Group Title TEV-50717 High-Dose TEV-50717 Low-Dose Placebo
    Arm/Group Description TEV-50717 tablets BID up to 48 mg/day orally for a total of 8 weeks TEV-50717 tablets BID up to 36 mg/day orally for a total of 8 weeks Placebo matched to TEV-50717 for a total of 8 weeks
    Measure Participants 52 54 51
    CDI-2 Parent Version
    -1.2
    (6.53)
    -3.8
    (6.34)
    -0.8
    (5.36)
    CDI-2 Self-Reported Version
    -2.0
    (4.13)
    -2.6
    (4.90)
    -0.4
    (4.99)
    10. Secondary Outcome
    Title Number of Participants at Baseline and Week 9 With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
    Description C-SSRS included responses for Suicidal Ideation or Suicidal Behavior in following 10 categories: 1 = Wish to be dead; 2 = Non-specific active suicidal thoughts; 3 = Active suicidal ideation with any methods (not plan) without intent to act; 4 = Active suicidal ideation with some intent to act, without specific plan; 5 = Active suicidal ideation with specific plan and intent; 6 = Preparatory acts or behavior; 7 = Aborted attempt; 8 = Interrupted attempt; 9 = Non-fatal suicide attempt; and 10 = Completed suicide. Number of participants with any suicidal ideation or suicidal behavior are reported. Any Suicidal ideation or Suicidal Behavior events reported as TEAEs along with all other reported TEAEs are included in the AE module.
    Time Frame Baseline, Week 9

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable at specified timepoints.
    Arm/Group Title TEV-50717 High-Dose TEV-50717 Low-Dose Placebo
    Arm/Group Description TEV-50717 tablets BID up to 48 mg/day orally for a total of 8 weeks TEV-50717 tablets BID up to 36 mg/day orally for a total of 8 weeks Placebo matched to TEV-50717 for a total of 8 weeks
    Measure Participants 52 54 51
    Baseline
    0
    0%
    0
    0%
    2
    3.8%
    Week 9
    0
    0%
    0
    0%
    0
    0%

    Adverse Events

    Time Frame Baseline (Day 1) to follow-up (Week 10)
    Adverse Event Reporting Description Safety analysis set included all participants who received at least 1 dose of study drug.
    Arm/Group Title TEV-50717 High-Dose TEV-50717 Low-Dose Placebo
    Arm/Group Description TEV-50717 tablets BID up to 48 mg/day orally for a total of 8 weeks TEV-50717 tablets BID up to 36 mg/day orally for a total of 8 weeks Placebo matched to TEV-50717 for a total of 8 weeks
    All Cause Mortality
    TEV-50717 High-Dose TEV-50717 Low-Dose Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/52 (0%) 0/54 (0%) 0/51 (0%)
    Serious Adverse Events
    TEV-50717 High-Dose TEV-50717 Low-Dose Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/52 (1.9%) 0/54 (0%) 0/51 (0%)
    Psychiatric disorders
    Attention deficit/hyperactivity disorder 1/52 (1.9%) 1 0/54 (0%) 0 0/51 (0%) 0
    Tic 1/52 (1.9%) 1 0/54 (0%) 0 0/51 (0%) 0
    Other (Not Including Serious) Adverse Events
    TEV-50717 High-Dose TEV-50717 Low-Dose Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/52 (36.5%) 16/54 (29.6%) 12/51 (23.5%)
    Gastrointestinal disorders
    Nausea 2/52 (3.8%) 2 3/54 (5.6%) 3 0/51 (0%) 0
    Vomiting 3/52 (5.8%) 3 1/54 (1.9%) 1 4/51 (7.8%) 5
    General disorders
    Fatigue 5/52 (9.6%) 6 1/54 (1.9%) 2 0/51 (0%) 0
    Infections and infestations
    Nasopharyngitis 6/52 (11.5%) 6 2/54 (3.7%) 2 3/51 (5.9%) 4
    Metabolism and nutrition disorders
    Increased appetite 4/52 (7.7%) 4 1/54 (1.9%) 1 0/51 (0%) 0
    Musculoskeletal and connective tissue disorders
    Pain in extremity 2/52 (3.8%) 2 0/54 (0%) 0 3/51 (5.9%) 4
    Nervous system disorders
    Headache 6/52 (11.5%) 8 8/54 (14.8%) 13 4/51 (7.8%) 4
    Somnolence 8/52 (15.4%) 11 2/54 (3.7%) 2 1/51 (2%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.

    Results Point of Contact

    Name/Title Director, Clinical Research
    Organization Teva Branded Pharmaceutical Products R&D, Inc.
    Phone 1-888-483-8279
    Email USMedInfo@tevapharm.com
    Responsible Party:
    Teva Branded Pharmaceutical Products R&D, Inc.
    ClinicalTrials.gov Identifier:
    NCT03571256
    Other Study ID Numbers:
    • TV50717-CNS-30060
    • 2017-002976-24
    First Posted:
    Jun 27, 2018
    Last Update Posted:
    Nov 9, 2021
    Last Verified:
    Nov 1, 2021