NCT03452943: ARTISTS1

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

Completed Phase 2, PHASE3 Results posted Last updated 9 November 2021

What this trial tests

Phase 2, PHASE3 trial testing TEV-50717 in Tourette Syndrome in 119 participants. Completed in 12 November 2019.

Timeline

5 February 2018

Primary endpoint
12 November 2019

12 November 2019

Quick facts

Lead sponsor	Teva Branded Pharmaceutical Products R&D, Inc.
Phase	Phase 2, PHASE3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	119
Start date	5 February 2018
Primary completion	12 November 2019
Estimated completion	12 November 2019
Sites	42 locations across Denmark, Russia, Serbia, Canada, United States, Spain

Drugs / interventions tested

• TEV-50717 — full drug profile →
• Placebo

Conditions studied

• Tourette Syndrome — all drugs for Tourette Syndrome →

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc. — full company profile →

Who can join

Adults 6 to 16, any sex, with Tourette Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in the TTS of the YGTSS at Week 12 Primary · Baseline, 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).

Group	Value	95% CI
TEV-50717	-9.1	± 1.28
Placebo	-8.4	± 1.25

Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score at Week 12 Secondary · Baseline, 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 (

Group	Value	95% CI
TEV-50717	-0.7	± 0.13
Placebo	-0.7	± 0.12

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

Group	Value	95% CI
TEV-50717	-0.7	± 0.18
Placebo	-0.4	± 0.14

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 Secondary · Baseline, 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

Group	Value	95% CI
TEV-50717	-9.9	± 2.37
Placebo	-8.8	± 2.27

Percentage of Participants With Adverse Events Secondary · Baseline (Day 1) to follow-up (Week 14)

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 th

Any AEs

Group	Value	95% CI
TEV-50717	65.5
Placebo	55.9

Treatment-related AEs

Group	Value	95% CI
TEV-50717	50.0
Placebo	20.3

Serious AEs

Group	Value	95% CI
TEV-50717	0
Placebo	0

AEs leading to discontinuation

Group	Value	95% CI
TEV-50717	1.7
Placebo	1.7

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline (Day 1) to follow-up (Week 14). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

TEV-50717

Serious: 0/58 (0%)

Deaths: 0/58

Placebo

Serious: 0/59 (0%)

Deaths: 0/59

Other adverse events (15 terms — click to expand)

Reaction	System	TEV-50717	Placebo
Fatigue	General disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Weight increased	Investigations	—	—
Headache	Nervous system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Somnolence	Nervous system disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Enuresis	Psychiatric disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Increased appetite	Metabolism and nutrition disorders	—	—
Anxiety	Psychiatric disorders	—	—
Depressed mood	Psychiatric disorders	—	—
Suicidal ideation	Psychiatric disorders	—	—

Data from ClinicalTrials.gov NCT03452943 adverse events section.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. A Comprehensive Review of Tic Disorders in Children.
   Ueda K, Black KJ. · · 2021 · cited 77× · PMID 34204991 · DOI 10.3390/jcm10112479
2. Safety and Efficacy of Flexible-Dose Deutetrabenazine in Children and Adolescents With Tourette Syndrome: A Randomized Clinical Trial.
   Jankovic J, Coffey B, Claassen DO, Jimenez-Shahed J, et al · · 2021 · cited 29× · PMID 34609495 · DOI 10.1001/jamanetworkopen.2021.28204
3. Safety and Efficacy of Long-Term Deutetrabenazine Use in Children and Adolescents with Tics Associated with Tourette Syndrome: An Open-Label Extension Study.
   Jankovic J, Coffey B, Claassen DO, Jimenez-Shahed J, et al · · 2023 · cited 8× · PMID 37772282 · DOI 10.1002/mdc3.13849
4. Emerging therapies and recent advances for Tourette syndrome.
   Chou CY, Agin-Liebes J, Kuo SH. · · 2023 · cited 8× · PMID 36691528 · DOI 10.1016/j.heliyon.2023.e12874
5. Treatment of dystonia and tics.
   Bellows S, Jankovic J. · · 2020 · cited 6× · PMID 34316614 · DOI 10.1016/j.prdoa.2019.11.005