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CompletedNCT03452943ARTISTS1Updated Nov 9, 2021Results posted

Alternatives for Reducing Tics in Tourette Syndrome (TS): A Study of TEV-50717 (Deutetrabenazine) for the Treatment of Tourette Syndrome in Children and Adolescents

A Phase 2/3 interventional study of TEV-50717 and Placebo in Tourette Syndrome, sponsored by Teva Branded Pharmaceutical Products R&D, Inc.. Completed at 42 sites in 6 countries. Open to participants aged 6 Years to 16 Years. Per ClinicalTrials.gov, last updated 2021-11-09.

Sponsored by Teva Branded Pharmaceutical Products R&D, Inc. · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
119
Allocation
Randomized
Ages
6 Years to 16 Years
Sex
All
01

Study summary

This is a study to evaluate the efficacy and safety of deutetrabenazine (TEV-50717) tablets for the reduction of motor and phonic tics associated with TS in children and adolescents 6 through 16 years of age.

02

Conditions studied

  • Tourette Syndrome

Keywords

  • Tourette Syndrome
  • adolescents
  • children
03

Who can participate

Ages eligible
6 Years to 16 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Participant is 6 to 16 years of age, inclusive.
  • Participant weighs at least 44 pounds (20 kilograms [kg]).
  • The participant's active tics are causing distress or impairment.
  • Participant is able to swallow study medication whole.
  • Participant is in good general health.
  • Women/girls of childbearing potential whose male partners are of childbearing potential must use contraception for the duration of the study.

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

Exclusion criteria

Exclusion Criteria:

  • Participant has a neurologic disorder other than TS that could obscure the evaluation of tics.
  • Participant has a confirmed diagnosis of bipolar disorder, schizophrenia, or another psychotic 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 received comprehensive behavioral intervention for tics (CBIT) for TS or cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD) within 4 weeks of screening.
  • Participant has an unstable or serious medical illness at screening or baseline.
  • Participant is pregnant or breastfeeding.

    • Additional criteria apply, please contact the investigator for more information.
04

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
119 participants (actual)

Study arms

  • Experimental
    TEV-50717

    TEV-50717 tablets twice daily (BID) up to 48 milligrams (mg)/day orally for a total of 12 weeks

    Drug: TEV-50717 · Drug: Placebo

  • Placebo comparator
    Placebo

    Placebo matched to TEV-50717 BID for a total of 12 weeks

    Drug: Placebo

Interventions

  • DrugTEV-50717

    6, 9, 12, 15, and 18 mg oral tablets

    Also known as: Deutetrabenazine

  • DrugPlacebo

    Placebo matched to TEV-50717 tablets will be taken BID for 12 weeks.

05

What researchers measure

Primary outcomes

  1. Change From Baseline in the TTS of the YGTSS at Week 12

    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 (5 levels: weeks 2, 4, 6, 9, and 12), 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 12

Secondary outcomes

  1. Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score at Week 12

    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 (5 levels: weeks 2, 4, 6, 9, and 12), 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 12

  2. Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score at Week 12

    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 12

  3. 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 12

    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 (5 levels: weeks 2, 4, 6, 9, and 12), 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 12

  4. Percentage of Participants With Adverse Events

    An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

    Time frame: Baseline (Day 1) to follow-up (Week 14)

06

Results

Posted Jun 4, 2020

Participant flow

Titration Period (7 Weeks)
Participant flow — Titration Period (7 Weeks)
MilestoneTEV-50717Placebo
Started5960
Safety analysis set5859
Modified itt (mitt) analysis set5859
Completed5456
Not completed54
Withdrew: Adverse event11
Withdrew: Protocol violation01
Withdrew: Withdrawal by subject32
Withdrew: Lost to follow-up10
Maintenance Period (5 Weeks)
Participant flow — Maintenance Period (5 Weeks)
MilestoneTEV-50717Placebo
Started5456
Completed5156
Not completed30
Withdrew: Adverse event10
Withdrew: Withdrawal by subject20

Outcome measures

PrimaryChange From Baseline in the TTS of the YGTSS at Week 12

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 (5 levels: weeks 2, 4, 6, 9, and 12), 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 12
Reported as:
Least squares mean · units on a scale
Change From Baseline in the TTS of the YGTSS at Week 12
units on a scaleTEV-50717Placebo
Change From Baseline in the TTS of the YGTSS at Week 12-9.1 ± 1.28-8.4 ± 1.25
Statistical analysis
  • TEV-50717 vs Placebo · Mixed Models Analysis · p = 0.692 (Threshold for significance at 0.05 level.) · Ls mean difference: -0.7 · 95% CI -4.1 to 2.8
SecondaryChange From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score at Week 12

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 (5 levels: weeks 2, 4, 6, 9, and 12), 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 12
Reported as:
Least squares mean · units on a scale
Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score at Week 12
units on a scaleTEV-50717Placebo
Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score at Week 12-0.7 ± 0.13-0.7 ± 0.12
SecondaryChange From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score at Week 12

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 12
Reported as:
Mean · units on a scale
Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score at Week 12
units on a scaleTEV-50717Placebo
Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score at Week 12-0.7 ± 0.18-0.4 ± 0.14
SecondaryChange 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 12

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 (5 levels: weeks 2, 4, 6, 9, and 12), 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 12
Reported as:
Least squares mean · units on a scale
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 12
units on a scaleTEV-50717Placebo
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 12-9.9 ± 2.37-8.8 ± 2.27
SecondaryPercentage of Participants With Adverse Events

An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Time frame:
Baseline (Day 1) to follow-up (Week 14)
Reported as:
Number · percentage of participants
Percentage of Participants With Adverse Events
percentage of participantsTEV-50717Placebo
Any AEs65.555.9
Treatment-related AEs50.020.3
Serious AEs00
AEs leading to discontinuation1.71.7

Adverse events

Collected over Baseline (Day 1) to follow-up (Week 14). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
TEV-507170/58 (0%)0/58 (0%)22/58 (37.9%)
Placebo0/59 (0%)0/59 (0%)23/59 (39%)
Most frequent other events
Showing 10 of 15
Most frequent other events
EventTEV-50717Placebo
FatigueGeneral disorders7/583/59
Weight increasedInvestigations7/581/59
Upper respiratory tract infectionInfections and infestations0/587/59
HeadacheNervous system disorders6/586/59
SomnolenceNervous system disorders5/581/59
NauseaGastrointestinal disorders4/585/59
DiarrhoeaGastrointestinal disorders4/581/59
EnuresisPsychiatric disorders4/580/59
VomitingGastrointestinal disorders3/583/59
PyrexiaGeneral disorders3/582/59

Baseline characteristics

ITT analysis set included all randomized participants.

Age, Continuous
Age, Continuous(years)TEV-50717PlaceboTotal
Mean11.5 ± 2.5211.5 ± 2.5911.5 ± 2.54
Sex: Female, Male
Sex: Female, Male(Participants)TEV-50717PlaceboTotal
Female6915
Male5351104
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)TEV-50717PlaceboTotal
Hispanic or Latino5813
Not Hispanic or Latino5150101
Unknown or Not Reported325
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)TEV-50717PlaceboTotal
White4953102
Black336
Asian112
Native American101
Multiple314
Other224
Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS)
Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS)(units on a scale)TEV-50717PlaceboTotal
Mean31.7 ± 5.8133.0 ± 5.9632.3 ± 5.89
07

Study locations

42 sites
  • Teva Investigational Site 046-0104
    Dothan, Alabama 36303, United States
  • Teva Investigational Site 046-0117
    Sun City, Arizona 85351, United States
  • Teva Investigational Site 046-0107
    Rogers, Arkansas 72758, United States
  • Teva Investigational Site 046-0126
    Anaheim, California 92805, United States
  • Teva Investigational Site 046-0101
    Sacramento, California 95815, United States
  • Teva Investigational Site 046-0111
    San Diego, California 92108, United States
  • Teva Investigational Site 046-0130
    Santa Ana, California 92705, United States
  • Teva Investigational Site 046-0132
    Miami, Florida 33155, United States
  • Teva Investigational Site 046-0115
    Orlando, Florida 32803, United States
  • Teva Investigational Site 046-0114
    Saint Petersburg, Florida 33701, United States
  • Teva Investigational Site 046-0116
    Atlanta, Georgia 30331, United States
  • Teva Investigational Site 046-0133
    Naperville, Illinois 60563, United States
  • Teva Investigational Site 046-0128
    Boston, Massachusetts 02114, United States
  • Teva Investigational Site 046-0110
    Saint Charles, Missouri 63304, United States
  • Teva Investigational Site 046-0134
    Lincoln, Nebraska 68526-9467, United States
  • Teva Investigational Site 046-0109
    Voorhees, New Jersey 08043, United States
  • Teva Investigational Site 046-0124
    New York, New York 10029, United States
  • Teva Investigational Site 046-0102
    Rochester, New York 14618, United States
  • Teva Investigational Site 046-0112
    Rochester, New York 14642, United States
  • Teva Investigational Site 046-0125
    Raleigh, North Carolina 27607, United States
  • Teva Investigational Site 046-0106
    Oklahoma City, Oklahoma 73116, United States
  • Teva Investigational Site 046-0113
    Dallas, Texas 75243, United States
  • Teva Investigational Site 046-0108
    Houston, Texas 77030, United States
  • Teva Investigational Site 046-0103
    Houston, Texas 77090, United States
  • Teva Investigational Site 046-0120
    San Antonio, Texas 78249, United States
  • Teva Investigational Site 046-0105
    Orem, Utah 84058, United States
  • Teva Investigational Site 046-0118
    Petersburg, Virginia 23805, United States
  • Teva Investigational Site 046-0201
    Ajax, Ontario L1Z0M1, Canada
  • Teva Investigational Site 046-0202
    Ottawa, Ontario K2G 1W2, Canada
  • Teva Investigational Site 046-0302
    Herlev, 2730, Denmark
  • Teva Investigational Site 046-0301
    Odense, 5000, Denmark
  • Teva Investigational Site 046-0702
    Stavropol, 355038, Russian Federation
  • Teva Investigational Site 046-0704
    Tomsk, 634050, Russian Federation
  • Teva Investigational Site 046-0703
    Voronezh, 394024, Russian Federation
  • Teva Investigational Site 046-1702
    Belgrade, 11000, Serbia
  • Teva Investigational Site 046-1703
    Belgrade, 11000, Serbia
  • Teva Investigational Site 046-1701
    Novi Sad, 21000, Serbia
  • Teva Investigational Site 046-0604
    Barcelona, 08041, Spain
  • Teva Investigational Site 046-0605
    Madrid, 28009, Spain
  • Teva Investigational Site 046-0602
    Madrid, 28922, Spain
  • Teva Investigational Site 046-0603
    Malaga, 29620, Spain
  • Teva Investigational Site 046-0601
    Sevilla, 41013, Spain
08

References and documents

Publications

  • Jankovic J, Coffey B, Claassen DO, Jimenez-Shahed J, Gertz BJ, Garofalo EA, Stamler DA, Wieman M, Savola JM, Gordon MF, Alexander J, Barkay H, Harary E. Safety and Efficacy of Flexible-Dose Deutetrabenazine in Children and Adolescents With Tourette Syndrome: A Randomized Clinical Trial. JAMA Netw Open. 2021 Oct 1;4(10):e2128204. doi: 10.1001/jamanetworkopen.2021.28204. PubMed 34609495 ↗

Study documents

  • Study protocol · Mar 25, 2019
  • Statistical analysis plan · Dec 2, 2019

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03452943
Lead sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
Collaborators
Nuvelution TS Pharma, Inc.
Responsible party
Sponsor
First posted
Mar 2, 2018
Start date
Feb 5, 2018
Primary completion
Nov 12, 2019
Completion
Nov 12, 2019
Results posted
Jun 4, 2020
Last update
Nov 9, 2021

Study contacts

Teva Medical Expert, MD
study director · Teva Branded Pharmaceutical Products R&D, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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