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

NCT03567291 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: TV50717-CNS-300472016-000630-22
• Study Type: interventional
• Target: 228
• Locations: 15 countries
• Sites: 76

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.

Conditions

Tourette Syndrome

Keywords

adolescents; children

Outcome Measures

Primary Outcomes (8)

• Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined

  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.

  Day 1 to Week 55

• Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II)

  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.

  Weeks 28 to 30

• Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score

  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.

  Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55

• Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score

  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.

  Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55

• Change From Randomized Withdrawal Baseline (Week 28) in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score at Week 30

  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.

  Week 28, Week 30

• 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

  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.

  Week 28, Week 30

• Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)

  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.

  Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55

• 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

  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.

  Week 28, Week 30

Secondary Outcomes (5)

• Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS)

  Baseline, Weeks 8, 15, 28, 41, 54, and 55

• Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score

  Baseline, Weeks 8, 15, 28, 41, 54, and 55

• Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score

  Baseline, Weeks 8, 15, 28, 41, 54, and 55

• 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

  Baseline, Weeks 6, 28, 34, 54

• Change From Randomized Withdrawal Baseline (Week 28) in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) to Week 30

  Week 28, Week 30

Study Arms (3)

TEV-50717- Part A

EXPERIMENTAL

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

TEV-50717- Part B RW

EXPERIMENTAL

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

Drug: TEV-50717

Placebo- Part B RW

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

TEV-50717 DRUG

6, 9, and 12 mg oral tablets

Also known as: deutetrabenazine, SD-809

TEV-50717- Part A; TEV-50717- Part B RW

Placebo DRUG

Placebo comparator

Placebo- Part B RW

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead
• Nuvelution TS Pharma, Inc.: collaborator

Study Sites (76)

Teva Investigational Site 046-0104

Dothan, Alabama, 36303, United States

Location

Teva Investigational Site 046-0107

Rogers, Arkansas, 72758, United States

Location

Teva Investigational Site 046-0126

Anaheim, California, 92805, United States

Location

Teva Investigational Site 046-0101

Sacramento, California, 95815, United States

Location

Teva Investigational Site 046-0111

San Diego, California, 92108, United States

Location

Teva Investigational Site 060-0160

Gainesville, Florida, 32608, United States

Location

Teva Investigational Site 060-0166

Gulf Breeze, Florida, 32561-4458, United States

Location

Teva Investigational Site 060-0161

Miami, Florida, 33136-2107, United States

Location

Teva Investigational Site 046-0115

Orlando, Florida, 32803, United States

Location

Teva Investigational Site 060-0153

Orlando, Florida, 32819, United States

Location

Teva Investigational Site 046-0114

St. Petersburg, Florida, 33701, United States

Location

Teva Investigational Site 046-0116

Atlanta, Georgia, 30331, United States

Location

Teva Investigational Site 060-0155

Chicago, Illinois, 60612, United States

Location

Teva Investigational Site 060-0164

Chicago, Illinois, 60634, United States

Location

Teva Investigational Site 046-0133

Naperville, Illinois, 60563, United States

Location

Teva Investigational Site 046-0128

Boston, Massachusetts, 02114, United States

Location

Teva Investigational Site 060-0170

Bridgeton, Missouri, 63044, United States

Location

Teva Investigational Site 046-0110

Saint Charles, Missouri, 63304, United States

Location

Teva Investigational Site 046-0134

Lincoln, Nebraska, 68526-9467, United States

Location

Teva Investigational Site 046-0109

Voorhees Township, New Jersey, 08043, United States

Location

Teva Investigational Site 046-0124

New York, New York, 10029, United States

Location

Teva Investigational Site 060-0154

New York, New York, 10036, United States

Location

Teva Investigational Site 046-0102

Rochester, New York, 14618, United States

Location

Teva Investigational Site 046-0106

Oklahoma City, Oklahoma, 73116, United States

Location

Teva Investigational Site 060-0169

Charleston, South Carolina, 29414-5834, United States

Location

Teva Investigational Site 060-0156

Nashville, Tennessee, 37232-2551, United States

Location

Teva Investigational Site 046-0113

Dallas, Texas, 75243, United States

Location

Teva Investigational Site 060-0163

Fort Worth, Texas, 76104, United States

Location

Teva Investigational Site 046-0108

Houston, Texas, 77030, United States

Location

Teva Investigational Site 046-0120

San Antonio, Texas, 78249, United States

Location

Teva Investigational Site 046-0105

Orem, Utah, 84058, United States

Location

Teva Investigational Site 046-0118

Petersburg, Virginia, 23805, United States

Location

Teva Investigational Site 060-0162

Everett, Washington, 98201-4077, United States

Location

Teva Investigational Site 060-1407

Buenos Aires, C1023AAB, Argentina

Location

Teva Investigational Site 060-1402

Buenos Aires, C1425AHQ, Argentina

Location

Teva Investigational Site 060-1403

La Plata, 1900, Argentina

Location

Teva Investigational Site 060-1404

Mendoza, 5500, Argentina

Location

Teva Investigational Site 060-1802

Liverpool, 2170, Australia

Location

Teva Investigational Site 046-0201

Ajax, Ontario, L1Z0M1, Canada

Location

Teva Investigational Site 046-0202

Ottawa, Ontario, K2G 1W2, Canada

Location

Teva Investigational Site 060-1503

Bello, 051050, Colombia

Location

Teva Investigational Site 060-1504

Pereira, 660003, Colombia

Location

Teva Investigational Site 046-0302

Herlev, 2730, Denmark

Location

Teva Investigational Site 046-0301

Odense, 5000, Denmark

Location

Teva Investigational Site 060-0901

Budapest, 1021, Hungary

Location

Teva Investigational Site 060-0902

Szeged, 6725, Hungary

Location

Teva Investigational Site 060-1005

Cagliari, 09121, Italy

Location

Teva Investigational Site 060-1001

Catania, 95123, Italy

Location

Teva Investigational Site 060-1003

Naples, 80131, Italy

Location

Teva Investigational Site 060-1601

Culiacán, 80020, Mexico

Location

Teva Investigational Site 060-1603

León, 37000, Mexico

Location

Teva Investigational Site 060-1602

Monterrey, 64460, Mexico

Location

Teva Investigational Site 060-1604

Monterrey, 64610, Mexico

Location

Teva Investigational Site 060-1104

Gdansk, 80-542, Poland

Location

Teva Investigational Site 060-1101

Katowice, 40-123, Poland

Location

Teva Investigational Site 060-1105

Krakow, 31503, Poland

Location

Teva Investigational Site 060-1102

Poznan, 60-693, Poland

Location

Teva Investigational Site 060-1103

Warsaw, 02-793, Poland

Location

Teva Investigational Site 046-0704

Tomsk, 634050, Russia

Location

Teva Investigational Site 046-0703

Voronezh, 394024, Russia

Location

Teva Investigational Site 046-1702

Belgrade, 11000, Serbia

Location

Teva Investigational Site 046-1703

Belgrade, 11000, Serbia

Location

Teva Investigational Site 046-1701

Novi Sad, 21000, Serbia

Location

Teva Investigational Site 060-1901

Seoul, 110-744, South Korea

Location

Teva Investigational Site 060-1903

Seoul, 138-736, South Korea

Location

Teva Investigational Site 060-1902

Seoul, 6351, South Korea

Location

Teva Investigational Site 046-0605

Madrid, 28009, Spain

Location

Teva Investigational Site 046-0602

Madrid, 28922, Spain

Location

Teva Investigational Site 046-0603

Málaga, 29620, Spain

Location

Teva Investigational Site 046-0601

Seville, 41013, Spain

Location

Teva Investigational Site 060-2003

Dnipropetrovsk, 49101, Ukraine

Location

Teva Investigational Site 060-2001

Kharkiv, 61068, Ukraine

Location

Teva Investigational Site 060-2002

Kharkiv, 61153, Ukraine

Location

Teva Investigational Site 060-2007

Kiev, 4080, Ukraine

Location

Teva Investigational Site 060-2005

Kyiv, 4209, Ukraine

Location

Teva Investigational Site 060-2006

Vinnytsia, 21005, Ukraine

Location

MeSH Terms

Conditions

Tourette Syndrome

Interventions

deutetrabenazine

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurodevelopmental Disorders; Mental Disorders

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products R&D, Inc.

USMedInfo@tevapharm.com

1-888-483-8279

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2018
• First Posted: June 25, 2018
• Study Start: May 25, 2018
• Primary Completion: May 15, 2020
• Study Completion: May 15, 2020
• Last Updated: November 9, 2021
• Results First Posted: March 23, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

AR (4); US (33); PL (5); CO (2); ME (4); IT (3); CA (2); ES (4); UA (6); AU (1); HU (2); KR (3); SE (3); RU (2); DK (2)