A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS) (ARTISTS2)
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| ClinicalTrials.gov Identifier: NCT03571256 |
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Recruitment Status :
Completed
First Posted : June 27, 2018
Results First Posted : June 9, 2020
Last Update Posted : November 9, 2021
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Sponsor:
Teva Branded Pharmaceutical Products R&D, Inc.
Collaborator:
Nuvelution TS Pharma, Inc.
Information provided by (Responsible Party):
Teva Branded Pharmaceutical Products R&D, Inc.
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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 |
|---|---|---|
| Tourette Syndrome | Drug: TEV-50717 Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| 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 : | December 9, 2019 |
| Actual Study Completion Date : | December 9, 2019 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Tourette syndrome
MedlinePlus related topics:
Tourette Syndrome
Drug Information available for:
Deutetrabenazine
| Arm | Intervention/treatment |
|---|---|
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Experimental: TEV-50717 High-Dose
TEV-50717 tablets twice daily (BID) up to 48 milligrams (mg)/day orally for a total of 8 weeks
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Drug: TEV-50717
6-, 9-, 12-, 15-, and 18 mg oral tablets
Other Name: AUSTEDO, Deutetrabenazine Drug: Placebo Placebo matched to TEV-50717 tablets will be taken BID. |
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Experimental: TEV-50717 Low-Dose
TEV-50717 tablets BID up to 36 mg/day orally for a total of 8 weeks
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Drug: TEV-50717
6-, 9-, 12-, 15-, and 18 mg oral tablets
Other Name: AUSTEDO, Deutetrabenazine Drug: Placebo Placebo matched to TEV-50717 tablets will be taken BID. |
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Placebo Comparator: Placebo
Placebo matched to TEV-50717 for a total of 8 weeks
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Drug: Placebo
Placebo matched to TEV-50717 tablets will be taken BID. |
Primary Outcome Measures :
- Change From Baseline in the TTS of the YGTSS at Week 8 Between High-Dose TEV-50717-Treated Participants and Placebo-Treated Participants [ Time Frame: 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 :
- 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 [ Time Frame: 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.
- Change From Baseline in the TTS of the YGTSS at Week 8 Between Low-Dose TEV-50717-Treated Participants and Placebo-Treated Participants [ Time Frame: 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.
- Change From Baseline in the TS-CGI Score at Week 8 Between Low-Dose TEV-50717-Treated Participants and Placebo-Treated Participants [ Time Frame: 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.
- 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 [ Time Frame: 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.
- Change From Baseline in the TS-PGII Score at Week 8 Between Low-Dose TEV-50717-Treated Participants and Placebo-Treated Participants [ Time Frame: 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.
- 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 [ Time Frame: 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.
- 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 [ Time Frame: 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.
- Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version and Self-reported Version) Total Score at Week 9 [ Time Frame: 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.
- 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) [ Time Frame: 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.
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| Ages Eligible for Study: | 6 Years to 16 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
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): NCT03571256
Locations
Show 56 study locations
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)
Documents provided by Teva Branded Pharmaceutical Products R&D, Inc.:
Documents provided by Teva Branded Pharmaceutical Products R&D, Inc.:
Study Protocol [PDF] May 5, 2019
Statistical Analysis Plan [PDF] January 14, 2020
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Teva Branded Pharmaceutical Products R&D, Inc. |
| ClinicalTrials.gov Identifier: | NCT03571256 |
| Other Study ID Numbers: |
TV50717-CNS-30060 2017-002976-24 ( EudraCT Number ) |
| First Posted: | June 27, 2018 Key Record Dates |
| Results First Posted: | June 9, 2020 |
| Last Update Posted: | November 9, 2021 |
| Last Verified: | November 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be reviewed for scientific merit, product approval status, and conflicts of interest. Patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please email USMedInfo@tevapharm.com to make your request. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Tourette Syndrome Syndrome Disease Pathologic Processes Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases |
Tic Disorders Movement Disorders Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Genetic Diseases, Inborn Neurodevelopmental Disorders Mental Disorders |