Clinical trial NCT03567291: Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Tourette Syndrome
Keywords: adolescents
children
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Nuvelution TS Pharma, Inc.
First posted: 2018-06-25
Enrollment: 228
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 \[Phase 3\]).

Eligibility 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

Primary outcomes:
measure: Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined
timeFrame: Day 1 to Week 55
measure: Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II)
timeFrame: Weeks 28 to 30
measure: Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score
timeFrame: Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55
measure: Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score
timeFrame: Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55
measure: Change From Randomized Withdrawal Baseline (Week 28) in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score at Week 30
timeFrame: Week 28, Week 30
measure: 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
timeFrame: Week 28, Week 30
measure: Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55
measure: 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
timeFrame: Week 28, Week 30
Secondary outcomes:
measure: Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS)
timeFrame: Baseline, Weeks 8, 15, 28, 41, 54, and 55
measure: Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score
timeFrame: Baseline, Weeks 8, 15, 28, 41, 54, and 55
measure: Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score
timeFrame: Baseline, Weeks 8, 15, 28, 41, 54, and 55
measure: 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
timeFrame: Baseline, Weeks 6, 28, 34, 54
measure: Change From Randomized Withdrawal Baseline (Week 28) in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) to Week 30
timeFrame: Week 28, Week 30
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Teva Investigational Site 046-0104
state: Alabama
city: Rogers
country: United States
facility: Teva Investigational Site 046-0107
state: Arkansas
city: Anaheim
country: United States
facility: Teva Investigational Site 046-0126
state: California
city: Sacramento
country: United States
facility: Teva Investigational Site 046-0101
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 046-0111
state: California
city: Gainesville
country: United States
facility: Teva Investigational Site 060-0160
state: Florida
city: Gulf Breeze
country: United States
facility: Teva Investigational Site 060-0166
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 060-0161
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 046-0115
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 060-0153
state: Florida
city: Saint Petersburg
country: United States
facility: Teva Investigational Site 046-0114
state: Florida
city: Atlanta
country: United States
facility: Teva Investigational Site 046-0116
state: Georgia
city: Chicago
country: United States
facility: Teva Investigational Site 060-0155
state: Illinois
city: Chicago
country: United States
facility: Teva Investigational Site 060-0164
state: Illinois
city: Naperville
country: United States
facility: Teva Investigational Site 046-0133
state: Illinois
city: Boston
country: United States
facility: Teva Investigational Site 046-0128
state: Massachusetts
city: Bridgeton
country: United States
facility: Teva Investigational Site 060-0170
state: Missouri
city: Saint Charles
country: United States
facility: Teva Investigational Site 046-0110
state: Missouri
city: Lincoln
country: United States
facility: Teva Investigational Site 046-0134
state: Nebraska
city: Voorhees
country: United States
facility: Teva Investigational Site 046-0109
state: New Jersey
city: New York
country: United States
facility: Teva Investigational Site 046-0124
state: New York
city: New York
country: United States
facility: Teva Investigational Site 060-0154
state: New York
city: Rochester
country: United States
facility: Teva Investigational Site 046-0102
state: New York
city: Oklahoma City
country: United States
facility: Teva Investigational Site 046-0106
state: Oklahoma
city: Charleston
country: United States
facility: Teva Investigational Site 060-0169
state: South Carolina
city: Nashville
country: United States
facility: Teva Investigational Site 060-0156
state: Tennessee
city: Dallas
country: United States
facility: Teva Investigational Site 046-0113
state: Texas
city: Fort Worth
country: United States
facility: Teva Investigational Site 060-0163
state: Texas
city: Houston
country: United States
facility: Teva Investigational Site 046-0108
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 046-0120
state: Texas
city: Orem
country: United States
facility: Teva Investigational Site 046-0105
state: Utah
city: Petersburg
country: United States
facility: Teva Investigational Site 046-0118
state: Virginia
city: Everett
country: United States
facility: Teva Investigational Site 060-0162
state: Washington
city: Buenos Aires
country: Argentina
facility: Teva Investigational Site 060-1407
city: Buenos Aires
country: Argentina
facility: Teva Investigational Site 060-1402
city: La Plata
country: Argentina
facility: Teva Investigational Site 060-1403
city: Mendoza
country: Argentina
facility: Teva Investigational Site 060-1404
city: Liverpool
country: Australia
facility: Teva Investigational Site 060-1802
city: Ajax
country: Canada
facility: Teva Investigational Site 046-0201
state: Ontario
city: Ottawa
country: Canada
facility: Teva Investigational Site 046-0202
state: Ontario
city: Bello
country: Colombia
facility: Teva Investigational Site 060-1503
city: Pereira
country: Colombia
facility: Teva Investigational Site 060-1504
city: Herlev
country: Denmark
facility: Teva Investigational Site 046-0302
city: Odense
country: Denmark
facility: Teva Investigational Site 046-0301
city: Budapest
country: Hungary
facility: Teva Investigational Site 060-0901
city: Szeged
country: Hungary
facility: Teva Investigational Site 060-0902
city: Cagliari
country: Italy
facility: Teva Investigational Site 060-1005
city: Catania
country: Italy
facility: Teva Investigational Site 060-1001
city: Naples
country: Italy
facility: Teva Investigational Site 060-1003
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 060-1901
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 060-1903
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 060-1902
city: Culiacan
country: Mexico
facility: Teva Investigational Site 060-1601
city: Leon
country: Mexico
facility: Teva Investigational Site 060-1603
city: Monterrey
country: Mexico
facility: Teva Investigational Site 060-1602
city: Monterrey
country: Mexico
facility: Teva Investigational Site 060-1604
city: Gdansk
country: Poland
facility: Teva Investigational Site 060-1104
city: Katowice
country: Poland
facility: Teva Investigational Site 060-1101
city: Krakow
country: Poland
facility: Teva Investigational Site 060-1105
city: Poznan
country: Poland
facility: Teva Investigational Site 060-1102
city: Warsaw
country: Poland
facility: Teva Investigational Site 060-1103
city: Tomsk
country: Russian Federation
facility: Teva Investigational Site 046-0704
city: Voronezh
country: Russian Federation
facility: Teva Investigational Site 046-0703
city: Belgrade
country: Serbia
facility: Teva Investigational Site 046-1702
city: Belgrade
country: Serbia
facility: Teva Investigational Site 046-1703
city: Novi Sad
country: Serbia
facility: Teva Investigational Site 046-1701
city: Madrid
country: Spain
facility: Teva Investigational Site 046-0605
city: Madrid
country: Spain
facility: Teva Investigational Site 046-0602
city: Malaga
country: Spain
facility: Teva Investigational Site 046-0603
city: Sevilla
country: Spain
facility: Teva Investigational Site 046-0601
city: Dnipropetrovsk
country: Ukraine
facility: Teva Investigational Site 060-2003
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 060-2001
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 060-2002
city: Kiev
country: Ukraine
facility: Teva Investigational Site 060-2007
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 060-2005
city: Vinnytsia
country: Ukraine
facility: Teva Investigational Site 060-2006
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: