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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03567291




Registration number
NCT03567291
Ethics application status
Date submitted
12/06/2018
Date registered
25/06/2018

Titles & IDs
Public title
Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
Scientific 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
Secondary ID [1] 0 0
2016-000630-22
Secondary ID [2] 0 0
TV50717-CNS-30047
Universal Trial Number (UTN)
Trial acronym
ARTISTS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tourette Syndrome 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Other mental health disorders
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TEV-50717
Treatment: Drugs - Placebo

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.

Experimental: TEV-50717- Part B RW - TEV-50717 is administered during Part B Randomized Drug Withdrawal (RW) 2-week period.

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


Treatment: Drugs: TEV-50717
6, 9, and 12 mg oral tablets

Treatment: Drugs: Placebo
Placebo comparator
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined
Assessment method [1] 0 0
Adverse events were analyzed for all participants in Parts A \& B combined as one group for this outcome measure. 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. Incudes clinically significant changes such as changes in vital signs or lab values. 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.
Timepoint [1] 0 0
Day 1 to Week 55
Primary outcome [2] 0 0
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II)
Assessment method [2] 0 0
Adverse events were analyzed for Part B for this outcome measure. 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. Incudes clinically significant changes such as changes in vital signs or lab values. 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.
Timepoint [2] 0 0
Weeks 28 to 30
Primary outcome [3] 0 0
Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55
Primary outcome [4] 0 0
Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55
Primary outcome [5] 0 0
Change From Randomized Withdrawal Baseline (Week 28) in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score at Week 30
Assessment method [5] 0 0
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.
Timepoint [5] 0 0
Week 28, Week 30
Primary outcome [6] 0 0
Change From Randomized Withdrawal Baseline (Week 28) in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score at Week 30
Assessment method [6] 0 0
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.
Timepoint [6] 0 0
Week 28, Week 30
Primary outcome [7] 0 0
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Assessment method [7] 0 0
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.
Timepoint [7] 0 0
Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55
Primary outcome [8] 0 0
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) at Randomized Withdrawal Baseline Visit (Week 28) and Week 30
Assessment method [8] 0 0
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.
Timepoint [8] 0 0
Week 28, Week 30
Secondary outcome [1] 0 0
Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS)
Assessment method [1] 0 0
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. Baseline is defined as the last measurement on or prior to the first dose of the open-label study medication.
Timepoint [1] 0 0
Baseline, Weeks 8, 15, 28, 41, 54, and 55
Secondary outcome [2] 0 0
Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score
Assessment method [2] 0 0
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. Baseline is defined as the last measurement on or prior to the first dose of the open-label study medication.
Timepoint [2] 0 0
Baseline, Weeks 8, 15, 28, 41, 54, and 55
Secondary outcome [3] 0 0
Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score
Assessment method [3] 0 0
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. Baseline is defined as the last measurement on or prior to the first dose of the open-label study medication.
Timepoint [3] 0 0
Baseline, Weeks 8, 15, 28, 41, 54, and 55
Secondary outcome [4] 0 0
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
Assessment method [4] 0 0
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. Baseline is defined as the last measurement on or prior to the first dose of the open-label study medication.
Timepoint [4] 0 0
Baseline, Weeks 6, 28, 34, 54
Secondary outcome [5] 0 0
Change From Randomized Withdrawal Baseline (Week 28) in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) to Week 30
Assessment method [5] 0 0
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. The model is an ANCOVA model that includes fixed effects for treatment group. The randomized withdrawal baseline TTS and age group at baseline (2 levels: 6-11 years, 12-18 years) are included as covariates.
Timepoint [5] 0 0
Week 28, Week 30

Eligibility
Key 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
Minimum age
6 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/05/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/05/2020
Sample size
Target
Accrual to date
Final
228
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Teva Investigational Site 060-1802 - Liverpool
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
Nebraska
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Oklahoma
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
United States of America
State/province [17] 0 0
Virginia
Country [18] 0 0
United States of America
State/province [18] 0 0
Washington
Country [19] 0 0
Argentina
State/province [19] 0 0
Buenos Aires
Country [20] 0 0
Argentina
State/province [20] 0 0
La Plata
Country [21] 0 0
Argentina
State/province [21] 0 0
Mendoza
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
Country [23] 0 0
Colombia
State/province [23] 0 0
Bello
Country [24] 0 0
Colombia
State/province [24] 0 0
Pereira
Country [25] 0 0
Denmark
State/province [25] 0 0
Herlev
Country [26] 0 0
Denmark
State/province [26] 0 0
Odense
Country [27] 0 0
Hungary
State/province [27] 0 0
Budapest
Country [28] 0 0
Hungary
State/province [28] 0 0
Szeged
Country [29] 0 0
Italy
State/province [29] 0 0
Cagliari
Country [30] 0 0
Italy
State/province [30] 0 0
Catania
Country [31] 0 0
Italy
State/province [31] 0 0
Naples
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Seoul
Country [33] 0 0
Mexico
State/province [33] 0 0
Culiacan
Country [34] 0 0
Mexico
State/province [34] 0 0
Leon
Country [35] 0 0
Mexico
State/province [35] 0 0
Monterrey
Country [36] 0 0
Poland
State/province [36] 0 0
Gdansk
Country [37] 0 0
Poland
State/province [37] 0 0
Katowice
Country [38] 0 0
Poland
State/province [38] 0 0
Krakow
Country [39] 0 0
Poland
State/province [39] 0 0
Poznan
Country [40] 0 0
Poland
State/province [40] 0 0
Warsaw
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Tomsk
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Voronezh
Country [43] 0 0
Serbia
State/province [43] 0 0
Belgrade
Country [44] 0 0
Serbia
State/province [44] 0 0
Novi Sad
Country [45] 0 0
Spain
State/province [45] 0 0
Madrid
Country [46] 0 0
Spain
State/province [46] 0 0
Malaga
Country [47] 0 0
Spain
State/province [47] 0 0
Sevilla
Country [48] 0 0
Ukraine
State/province [48] 0 0
Dnipropetrovsk
Country [49] 0 0
Ukraine
State/province [49] 0 0
Kharkiv
Country [50] 0 0
Ukraine
State/province [50] 0 0
Kiev
Country [51] 0 0
Ukraine
State/province [51] 0 0
Kyiv
Country [52] 0 0
Ukraine
State/province [52] 0 0
Vinnytsia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Teva Branded Pharmaceutical Products R&D, Inc.
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Nuvelution TS Pharma, Inc.
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Teva Medical Expert, MD
Address 0 0
Teva Branded Pharmaceutical Products R&D, Inc.
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03567291