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Alternatives for Reducing Tics in Tourette Syndrome (TS): A Study of TEV-50717 (Deutetrabenazine) for the Treatment of Tourette Syndrome in Children and Adolescents (ARTISTS1)

Primary Purpose

Tourette Syndrome

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TEV-50717
Placebo
Sponsored by
Teva Branded Pharmaceutical Products R&D, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tourette Syndrome focused on measuring Tourette Syndrome, adolescents, children

Eligibility Criteria

6 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

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:

  • 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.

Sites / Locations

  • Teva Investigational Site 046-0104
  • Teva Investigational Site 046-0117
  • Teva Investigational Site 046-0107
  • Teva Investigational Site 046-0126
  • Teva Investigational Site 046-0101
  • Teva Investigational Site 046-0111
  • Teva Investigational Site 046-0130
  • Teva Investigational Site 046-0132
  • Teva Investigational Site 046-0115
  • Teva Investigational Site 046-0114
  • Teva Investigational Site 046-0116
  • Teva Investigational Site 046-0133
  • Teva Investigational Site 046-0128
  • Teva Investigational Site 046-0110
  • Teva Investigational Site 046-0134
  • Teva Investigational Site 046-0109
  • Teva Investigational Site 046-0124
  • Teva Investigational Site 046-0102
  • Teva Investigational Site 046-0112
  • Teva Investigational Site 046-0125
  • Teva Investigational Site 046-0106
  • Teva Investigational Site 046-0113
  • Teva Investigational Site 046-0108
  • Teva Investigational Site 046-0103
  • Teva Investigational Site 046-0120
  • Teva Investigational Site 046-0105
  • Teva Investigational Site 046-0118
  • Teva Investigational Site 046-0201
  • Teva Investigational Site 046-0202
  • Teva Investigational Site 046-0302
  • Teva Investigational Site 046-0301
  • Teva Investigational Site 046-0702
  • Teva Investigational Site 046-0704
  • Teva Investigational Site 046-0703
  • Teva Investigational Site 046-1702
  • Teva Investigational Site 046-1703
  • Teva Investigational Site 046-1701
  • Teva Investigational Site 046-0604
  • Teva Investigational Site 046-0605
  • Teva Investigational Site 046-0602
  • Teva Investigational Site 046-0603
  • Teva Investigational Site 046-0601

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

TEV-50717

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
February 26, 2018
Last Updated
November 5, 2021
Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
Collaborators
Nuvelution TS Pharma, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03452943
Brief Title
Alternatives for Reducing Tics in Tourette Syndrome (TS): A Study of TEV-50717 (Deutetrabenazine) for the Treatment of Tourette Syndrome in Children and Adolescents
Acronym
ARTISTS1
Official Title
A Randomized, Double-blind, Placebo-controlled Study of TEV-50717 (Deutetrabenazine) for the Treatment of Tourette Syndrome in Children and Adolescents
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
February 5, 2018 (Actual)
Primary Completion Date
November 12, 2019 (Actual)
Study Completion Date
November 12, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
Collaborators
Nuvelution TS Pharma, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tourette Syndrome
Keywords
Tourette Syndrome, adolescents, children

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
119 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TEV-50717
Arm Type
Experimental
Arm Description
TEV-50717 tablets twice daily (BID) up to 48 milligrams (mg)/day orally for a total of 12 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo matched to TEV-50717 BID for a total of 12 weeks
Intervention Type
Drug
Intervention Name(s)
TEV-50717
Other Intervention Name(s)
Deutetrabenazine
Intervention Description
6, 9, 12, 15, and 18 mg oral tablets
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo matched to TEV-50717 tablets will be taken BID for 12 weeks.
Primary Outcome Measure Information:
Title
Change From Baseline in the TTS of the YGTSS at Week 12
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 (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 Outcome Measure Information:
Title
Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score at Week 12
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 (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
Title
Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score at Week 12
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 12
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 12
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 (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
Title
Percentage of Participants With Adverse Events
Description
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Teva Medical Expert, MD
Organizational Affiliation
Teva Branded Pharmaceutical Products R&D, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Teva Investigational Site 046-0104
City
Dothan
State/Province
Alabama
ZIP/Postal Code
36303
Country
United States
Facility Name
Teva Investigational Site 046-0117
City
Sun City
State/Province
Arizona
ZIP/Postal Code
85351
Country
United States
Facility Name
Teva Investigational Site 046-0107
City
Rogers
State/Province
Arkansas
ZIP/Postal Code
72758
Country
United States
Facility Name
Teva Investigational Site 046-0126
City
Anaheim
State/Province
California
ZIP/Postal Code
92805
Country
United States
Facility Name
Teva Investigational Site 046-0101
City
Sacramento
State/Province
California
ZIP/Postal Code
95815
Country
United States
Facility Name
Teva Investigational Site 046-0111
City
San Diego
State/Province
California
ZIP/Postal Code
92108
Country
United States
Facility Name
Teva Investigational Site 046-0130
City
Santa Ana
State/Province
California
ZIP/Postal Code
92705
Country
United States
Facility Name
Teva Investigational Site 046-0132
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Teva Investigational Site 046-0115
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Teva Investigational Site 046-0114
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Teva Investigational Site 046-0116
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30331
Country
United States
Facility Name
Teva Investigational Site 046-0133
City
Naperville
State/Province
Illinois
ZIP/Postal Code
60563
Country
United States
Facility Name
Teva Investigational Site 046-0128
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Teva Investigational Site 046-0110
City
Saint Charles
State/Province
Missouri
ZIP/Postal Code
63304
Country
United States
Facility Name
Teva Investigational Site 046-0134
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68526-9467
Country
United States
Facility Name
Teva Investigational Site 046-0109
City
Voorhees
State/Province
New Jersey
ZIP/Postal Code
08043
Country
United States
Facility Name
Teva Investigational Site 046-0124
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Teva Investigational Site 046-0102
City
Rochester
State/Province
New York
ZIP/Postal Code
14618
Country
United States
Facility Name
Teva Investigational Site 046-0112
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Teva Investigational Site 046-0125
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Teva Investigational Site 046-0106
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73116
Country
United States
Facility Name
Teva Investigational Site 046-0113
City
Dallas
State/Province
Texas
ZIP/Postal Code
75243
Country
United States
Facility Name
Teva Investigational Site 046-0108
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Teva Investigational Site 046-0103
City
Houston
State/Province
Texas
ZIP/Postal Code
77090
Country
United States
Facility Name
Teva Investigational Site 046-0120
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78249
Country
United States
Facility Name
Teva Investigational Site 046-0105
City
Orem
State/Province
Utah
ZIP/Postal Code
84058
Country
United States
Facility Name
Teva Investigational Site 046-0118
City
Petersburg
State/Province
Virginia
ZIP/Postal Code
23805
Country
United States
Facility Name
Teva Investigational Site 046-0201
City
Ajax
State/Province
Ontario
ZIP/Postal Code
L1Z0M1
Country
Canada
Facility Name
Teva Investigational Site 046-0202
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K2G 1W2
Country
Canada
Facility Name
Teva Investigational Site 046-0302
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Teva Investigational Site 046-0301
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Teva Investigational Site 046-0702
City
Stavropol
ZIP/Postal Code
355038
Country
Russian Federation
Facility Name
Teva Investigational Site 046-0704
City
Tomsk
ZIP/Postal Code
634050
Country
Russian Federation
Facility Name
Teva Investigational Site 046-0703
City
Voronezh
ZIP/Postal Code
394024
Country
Russian Federation
Facility Name
Teva Investigational Site 046-1702
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Teva Investigational Site 046-1703
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Teva Investigational Site 046-1701
City
Novi Sad
ZIP/Postal Code
21000
Country
Serbia
Facility Name
Teva Investigational Site 046-0604
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Teva Investigational Site 046-0605
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Teva Investigational Site 046-0602
City
Madrid
ZIP/Postal Code
28922
Country
Spain
Facility Name
Teva Investigational Site 046-0603
City
Malaga
ZIP/Postal Code
29620
Country
Spain
Facility Name
Teva Investigational Site 046-0601
City
Sevilla
ZIP/Postal Code
41013
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
34609495
Citation
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.
Results Reference
derived

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

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