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Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents (ARTISTS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03567291
Recruitment Status : Active, not recruiting
First Posted : June 25, 2018
Last Update Posted : May 27, 2020
Sponsor:
Collaborator:
Nuvelution TS Pharma, Inc.
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products R&D, Inc. )

Brief Summary:
This is an otherwise open-label, single-arm study that includes a 2-week, double-blind, placebo controlled, randomized drug withdrawal period followed by a 3 week blinded maintenance or re-titration, and then a maintenance period. This study aims to evaluate the safety and efficacy of TEV-50717 tablets in patients with tics associated with TS who have previously completed participation in any of the parent studies.

Condition or disease Intervention/treatment Phase
Tourette Syndrome Drug: TEV-50717 Drug: Placebo Phase 3

Detailed Description:
This is an otherwise open-label, single-arm study (Part A) that includes a 2-week, double-blind, placebo controlled, randomized drug withdrawal period (Part B) followed by a 3 week blinded maintenance or re-titration (Part A resumed), and then a maintenance period. This study aims to evaluate the safety and efficacy of TEV-50717 tablets in patients with tics associated with TS who have previously completed participation in any of the parent studies (SD-809-C-17 [Phase 1b], TV50717-CNS 30046 [Phase 2/3], or TV50717-CNS 30060 [Phase 3]).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 228 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Open-Label, Long-Term Safety Study Including a Double-Blind, Placebo-Controlled, Randomized Withdrawal Period of TEV-50717 (Deutetrabenazine) for the Treatment of Tourette Syndrome in Children and Adolescents
Actual Study Start Date : May 25, 2018
Estimated Primary Completion Date : January 15, 2021
Estimated Study Completion Date : January 15, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TEV-50717- Part A
All patients will undergo TEV-50717 dose titration in this study. Patients will receive 6 mg of TEV-50717 with food on the evening of day 1. The titration scheme and maximum dose will be determined by body weight and cytochrome P450 2D6 (CYP2D6) impairment status from the parent study.
Drug: TEV-50717
6, 9, and 12 mg oral tablets
Other Name: deutetrabenazine, SD-809

Experimental: TEV-50717- Part B RW
TEV-50717 is administered during Part B Randomized Drug Withdrawal (RW) 2-week period.
Drug: TEV-50717
6, 9, and 12 mg oral tablets
Other Name: deutetrabenazine, SD-809

Placebo Comparator: Placebo- Part B RW
Placebo is administered during Part B Randomized Drug Withdrawal (RW) 2-week period only.
Drug: Placebo
Placebo comparator




Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: 55 weeks ]
    Incidence of adverse events (AEs), serious AEs, severe AEs, drug related AEs, AEs leading to withdrawal.


Secondary Outcome Measures :
  1. Change in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) [ Time Frame: Screening, day 1: and weeks 2, 4, 6, 8, 15, 34, 41, 54, and 55 ]
    When scoring the YGTSS, the tool gives ratings in 5 domains: Total Motor Tic Score, Total Verbal Tic Score, Total Tic Score (Motor + Verbal), Overall Impairment Rating, and Global Severity Score. When calculating the Global Severity score, it is found by adding together the total motor, verbal and impairment scores. The Total Tic Severity Score has a range of 0-50, and the Global Severity Score has a range of 0- 100. A higher score on all scales suggests a more severe Tic, or a greater impact the Tic has on the person's life

  2. Change in the Tourette Syndrome-Clinical Global Impression (TS-CGI) score [ Time Frame: Screening, day 1: and weeks 2, 4, 6, 8, 15, 34, 41, 54, and 55 ]
    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 patient's quality of life. The TS-CGI is rated as follows: 1 (normal), 2 (borderline), 3 (mild), 4 (moderate), 5 (marked), 6 (severe), and 7 (extreme).

  3. Change in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) score [ Time Frame: Screening, day 1: and weeks 2, 4, 6, 8, 15, 34, 41, 54, and 55 ]
    The TS-PGII is a single-item questionnaire that asks the patient to assess the degree of impact due to current tics. The TS-PGII uses a 5-point scale, ranging from not at all (1) to very much (5), to assess overall response to therapy.

  4. Change in the Child and Adolescent Gilles de la Tourette Syndrome - Quality of Life (C&A-GTS-QOL) activities of daily living (ADL) subscale score [ Time Frame: Screening, day 1: and weeks 2, 4, 6, 8, 15, 34, 41, 54, and 55 ]
    The C&A-GTS-QOL is a 27-item questionnaire specific to TS patients that asks the patient to assess the extent to which their quality of life is impacted by their symptoms. The C&AGTS- QOL contains 4 subscales (psychological, physical, obsessional, and cognitive) and uses a 5-point Likert scale ranging from no problem to extreme problem. Patients will also be asked how satisfied they feel overall with their life at that moment by using a VAS scale between 0 and 100

  5. Change in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) [ Time Frame: Weeks 28-30 ]
    When scoring the YGTSS, the tool gives ratings in 5 domains: Total Motor Tic Score, Total Verbal Tic Score, Total Tic Score (Motor + Verbal), Overall Impairment Rating, and Global Severity Score. When calculating the Global Severity score, it is found by adding together the total motor, verbal and impairment scores. The Total Tic Severity Score has a range of 0-50, and the Global Severity Score has a range of 0- 100. A higher score on all scales suggests a more severe Tic, or a greater impact the Tic has on the person's life.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient is younger than 18 years of age on day 1
  • Patient weighs at least 44 pounds (20 kg)
  • The patient's active tics are causing distress or impairment
  • Patient is able to swallow study medication whole
  • Patient 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:

  • Patient is 18 years of age or older.
  • Patient has a neurologic disorder other than TS that could obscure the evaluation of tics.
  • The patient's predominant movement disorder is stereotypy (coordinated movements that repeat continually and identically) associated with autism spectrum disorder.
  • Patient has a confirmed diagnosis of bipolar disorder, schizophrenia, or another psychotic disorder.
  • Patient has clinically significant depression at screening or day 1. Note: Patients receiving antidepressant therapy may be enrolled if on a stable dose for at least 6 weeks before screening.
  • Patient has a history of suicidal intent or related behaviors within 2 years of screening
  • Patient has a history of a previous actual, interrupted, or aborted suicide attempt.
  • Patient has a first-degree relative who has completed suicide.
  • Patient has clinically significant obsessive-compulsive disorder (OCD) on day 1 that, in the opinion of the investigator, is the primary cause of impairment.
  • Patient has received comprehensive behavioral intervention for tics for TS or cognitive behavioral therapy for OCD within 4 weeks of screening.
  • Patient has received treatment with deep brain stimulation, transmagnetic stimulation, or transcranial direct current stimulation for reduction of tics within 4 weeks of the screening visit.
  • Patient has an unstable or serious medical illness at screening or day 1
  • Patients with a history of torsade de pointes, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure.
  • Patient has received a monoamine oxidase inhibitor within 14 days of the day 1 visit.
  • Patient has participated in an investigational drug or device study (with the exception of Study SD-809-C-17, Study TV50717-CNS-30046, or Study TV50717-CNS-30060) and received IMP/intervention within 30 days or 5 drug half-lives of day 1, whichever is longer.
  • The patient is a pregnant or lactating female, or plans to become pregnant during the study.
  • Patient has a history of, or acknowledges, alcohol-related disorder in the previous 12 months -- 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): NCT03567291


Locations
Show Show 23 study locations
Sponsors and Collaborators
Teva Branded Pharmaceutical Products R&D, Inc.
Nuvelution TS Pharma, Inc.
Investigators
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Study Director: Teva Medical Expert, MD Teva Pharmaceuticals USA
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Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
ClinicalTrials.gov Identifier: NCT03567291    
Other Study ID Numbers: TV50717-CNS-30047
2016-000630-22 ( EudraCT Number )
First Posted: June 25, 2018    Key Record Dates
Last Update Posted: May 27, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products R&D, Inc. ):
adolescents
children
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