Tourette Syndrome
Conditions
Keywords
adolescents, children
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 \[Phase 3\]).
Interventions
DRUGTEV-50717
6, 9, and 12 mg oral tablets
DRUGPlacebo
Placebo comparator
Sponsors
Nuvelution TS Pharma, Inc.
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Week 28, 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. |
| Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score | Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55 | 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. |
| Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score | Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55 | 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. |
| Change From Randomized Withdrawal Baseline (Week 28) in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score at Week 30 | Week 28, 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. |
| 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 | Week 28, 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. |
| Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55 | 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. |
| Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined | Day 1 to Week 55 | 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. |
| Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II) | Weeks 28 to 30 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score | Baseline, Weeks 8, 15, 28, 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 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. |
| Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score | Baseline, Weeks 8, 15, 28, 41, 54, and 55 | 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. |
| 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 | 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. |
| 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 | 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. |
| Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) | Baseline, Weeks 8, 15, 28, 41, 54, and 55 | 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. |
Countries
Argentina, Australia, Canada, Colombia, Denmark, Hungary, Italy, Mexico, Poland, Russia, Serbia, South Korea, Spain, Ukraine, United States
Participant flow
Recruitment details
228 participants with Tourette Syndrome were enrolled after completing one of two eligible parent studies.
Pre-assignment details
Period I (Part A) included a 28-week open-label period with a 7-week titration period followed by a maintenance period. Period II (Part B) included a two-week randomized drug withdrawal period (Weeks 28-30) in which participants were administered their current TEV50717 dose or placebo. Participants were re-titrated to TEV-50717 from Weeks 31-34. In Period III (Part A resumed), participants continued their open-label maintenance dose of TEV50717.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants underwent TEV-50717 dose titration in this study. They received 6 mg of TEV-50717 with food on the evening of day 1. The titration scheme and maximum dose were determined by body weight and cytochrome P450 2D6 (CYP2D6) impairment status from the parent study. | 228 |
| Total | 228 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period I | Adverse Event | 14 | 0 | 0 | 0 |
| Period I | Lost to Follow-up | 2 | 0 | 0 | 0 |
| Period I | Missing or unknown | 7 | 0 | 0 | 0 |
| Period I | Protocol Violation | 1 | 0 | 0 | 0 |
| Period I | Terminated by sponsor | 44 | 0 | 0 | 0 |
| Period I | Withdrawal by Subject | 23 | 0 | 0 | 0 |
| Period II | Adverse Event | 0 | 1 | 0 | 0 |
| Period II | Missing or unknown | 0 | 2 | 1 | 0 |
| Period III | Adverse Event | 0 | 0 | 0 | 4 |
| Period III | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Period III | Missing or unknown | 0 | 0 | 0 | 8 |
| Period III | Terminated by sponsor | 0 | 0 | 0 | 68 |
| Period III | Withdrawal by Subject | 0 | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 12 Years STANDARD_DEVIATION 2.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 186 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants |
| Race/Ethnicity, Customized Black | 4 Participants |
| Race/Ethnicity, Customized Native American | 5 Participants |
| Race/Ethnicity, Customized Other | 15 Participants |
| Race/Ethnicity, Customized White | 197 Participants |
| Sex/Gender, Customized Participants Female | 45 Participants |
| Sex/Gender, Customized Participants Male | 182 Participants |
| Sex/Gender, Customized Participants Unknown | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 227 |
| other Total, other adverse events | 108 / 227 |
| serious Total, serious adverse events | 2 / 227 |
Outcome results
Primary
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.
Time frame: Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55
Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score | CDI-2 Parent Version Week 2 | -0.7 Units On A Scale | Standard Deviation 4.26 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score | CDI-2 Parent Version Week 4 | -1.5 Units On A Scale | Standard Deviation 4.39 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score | CDI-2 Parent Version Week 8 | -1.5 Units On A Scale | Standard Deviation 5 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score | CDI-2 Parent Version Week 15 | -1.2 Units On A Scale | Standard Deviation 5.79 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score | CDI-2 Parent Version Week 28 | -1.1 Units On A Scale | Standard Deviation 5.52 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score | CDI-2 Parent Version Week 34 | -1.0 Units On A Scale | Standard Deviation 6.08 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score | CDI-2 Parent Version Week 41 | -1.1 Units On A Scale | Standard Deviation 5.92 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score | CDI-2 Parent Version Week 54 | -0.3 Units On A Scale | Standard Deviation 5.83 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score | CDI-2 Parent Version Week 55 | -0.9 Units On A Scale | Standard Deviation 4.34 |
Primary
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.
Time frame: Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55
Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score | CDI-2 Self-reported Version Week 8 | -0.3 Units On A Scale | Standard Deviation 4.35 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score | CDI-2 Self-reported Version Week 34 | -0.5 Units On A Scale | Standard Deviation 4.61 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score | CDI-2 Self-reported Version Week 2 | -0.3 Units On A Scale | Standard Deviation 3.41 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score | CDI-2 Self-reported Version Week 4 | -0.5 Units On A Scale | Standard Deviation 3.57 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score | CDI-2 Self-reported Version Week 15 | -0.3 Units On A Scale | Standard Deviation 4.83 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score | CDI-2 Self-reported Version Week 28 | 0.0 Units On A Scale | Standard Deviation 4.65 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score | CDI-2 Self-reported Version Week 41 | -0.7 Units On A Scale | Standard Deviation 4.74 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score | CDI-2 Self-reported Version Week 54 | -0.5 Units On A Scale | Standard Deviation 4.01 |
| TEV-50717 | Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score | CDI-2 Self-reported Version Week 55 | -0.3 Units On A Scale | Standard Deviation 4.52 |
Primary
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.
Time frame: Week 28, Week 30
Population: Population includes all participants who completed Period I, were randomized in Period II, and who were administered any study drug in the randomized withdrawal period, Part B (Period II). Here, 'number analyzed' signifies participants evaluable for specified categories.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TEV-50717 | Change From Randomized Withdrawal Baseline (Week 28) in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score at Week 30 | -0.2 Units On A Scale | Standard Deviation 4.68 |
| Randomized Placebo | Change From Randomized Withdrawal Baseline (Week 28) in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score at Week 30 | 0.6 Units On A Scale | Standard Deviation 3.62 |
Primary
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.
Time frame: Week 28, Week 30
Population: Population includes all participants who completed Period I, were randomized in Period II, and who were administered any study drug in the randomized withdrawal period, Part B (Period II). Here, 'number analyzed' signifies participants evaluable for specified categories.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TEV-50717 | 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 | -0.4 Units On A Scale | Standard Deviation 3.3 |
| Randomized Placebo | 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 | -0.6 Units On A Scale | Standard Deviation 3.08 |
Primary
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.
Time frame: Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55
Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TEV-50717 | Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Baseline | 0 Participants |
| TEV-50717 | Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Week 2 | 0 Participants |
| TEV-50717 | Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Week 41 | 1 Participants |
| TEV-50717 | Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Week 4 | 2 Participants |
| TEV-50717 | Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Week 8 | 0 Participants |
| TEV-50717 | Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Week 15 | 1 Participants |
| TEV-50717 | Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Week 28 | 0 Participants |
| TEV-50717 | Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Week 34 | 0 Participants |
| TEV-50717 | Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Week 54 | 0 Participants |
| TEV-50717 | Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Week 55 | 0 Participants |
Primary
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.
Time frame: Week 28, Week 30
Population: Population includes all participants who completed Period I, were randomized in Period II, and who were administered any study drug in the randomized withdrawal period, Part B (Period II). Here, 'number analyzed' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TEV-50717 | 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 | Week 30 | 0 Participants |
| TEV-50717 | 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 | Week 28 | 0 Participants |
| Randomized Placebo | 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 | Week 28 | 0 Participants |
| Randomized Placebo | 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 | Week 30 | 0 Participants |
Primary
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.
Time frame: Day 1 to Week 55
Population: Safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TEV-50717 | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined | At least one adverse event | 161 Participants |
| TEV-50717 | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined | At least one serious adverse event | 2 Participants |
| TEV-50717 | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined | At least one AE related to investigational product | 95 Participants |
| TEV-50717 | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined | At least one severe adverse event | 6 Participants |
| TEV-50717 | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined | At least one adverse event leading to withdrawal | 14 Participants |
Primary
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.
Time frame: Weeks 28 to 30
Population: Population includes all participants who completed Period I, were randomized in Period II, and who were administered any study drug in the randomized withdrawal period, Part B (Period II).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TEV-50717 | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II) | At least one serious adverse event | 0 Participants |
| TEV-50717 | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II) | At least one AE related to investigational product | 6 Participants |
| TEV-50717 | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II) | At least one severe adverse event | 0 Participants |
| TEV-50717 | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II) | At least one adverse event leading to withdrawal | 0 Participants |
| TEV-50717 | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II) | At least one adverse event | 16 Participants |
| Randomized Placebo | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II) | At least one adverse event leading to withdrawal | 0 Participants |
| Randomized Placebo | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II) | At least one serious adverse event | 0 Participants |
| Randomized Placebo | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II) | At least one severe adverse event | 0 Participants |
| Randomized Placebo | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II) | At least one AE related to investigational product | 1 Participants |
| Randomized Placebo | Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II) | At least one adverse event | 6 Participants |
Secondary
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
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.
Time frame: Baseline, Weeks 6, 28, 34, 54
Population: Data were not collected during Part B (Period II). ITT analysis set includes all participants enrolled in part I. Here, 'number analyzed' signifies participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TEV-50717 | 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 | Week 6 | -4.9 Units on a scale | Standard Error 1.12 |
| TEV-50717 | 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 | Week 28 | -4.4 Units on a scale | Standard Error 1.48 |
| TEV-50717 | 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 | Week 54 | -2.7 Units on a scale | Standard Error 2.1 |
| TEV-50717 | 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 | Week 34 | -5.9 Units on a scale | Standard Error 1.82 |
Secondary
Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score
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.
Time frame: Baseline, Weeks 8, 15, 28, 41, 54, and 55
Population: Data were not collected during Part B (Period II). ITT analysis set includes all participants enrolled in part I. Here, 'number analyzed' signifies participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TEV-50717 | Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score | Week 28 | -0.6 Units on a scale | Standard Error 0.08 |
| TEV-50717 | Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score | Week 41 | -0.6 Units on a scale | Standard Error 0.1 |
| TEV-50717 | Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score | Week 54 | -0.8 Units on a scale | Standard Error 0.16 |
| TEV-50717 | Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score | Week 55 | -0.4 Units on a scale | Standard Error 0.15 |
| TEV-50717 | Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score | Week 8 | -0.7 Units on a scale | Standard Error 0.06 |
| TEV-50717 | Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score | Week 15 | -0.7 Units on a scale | Standard Error 0.06 |
Secondary
Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score
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.
Time frame: Baseline, Weeks 8, 15, 28, 41, 54, and 55
Population: Data were not collected during Part B (Period II). ITT analysis set includes all participants enrolled in part I. Here, 'number analyzed' signifies participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TEV-50717 | Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score | Week 41 | -0.6 Units on a scale | Standard Error 0.12 |
| TEV-50717 | Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score | Week 54 | -0.5 Units on a scale | Standard Error 0.16 |
| TEV-50717 | Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score | Week 8 | -0.5 Units on a scale | Standard Error 0.07 |
| TEV-50717 | Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score | Week 15 | -0.5 Units on a scale | Standard Error 0.08 |
| TEV-50717 | Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score | Week 28 | -0.5 Units on a scale | Standard Error 0.09 |
| TEV-50717 | Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score | Week 55 | -0.1 Units on a scale | Standard Error 0.14 |
Secondary
Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS)
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.
Time frame: Baseline, Weeks 8, 15, 28, 41, 54, and 55
Population: ITT analysis set includes all participants enrolled in part I. Here, 'number analyzed' signifies participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TEV-50717 | Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) | Week 8 | -6.9 Units on a scale | Standard Error 0.58 |
| TEV-50717 | Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) | Week 15 | -7.8 Units on a scale | Standard Error 0.58 |
| TEV-50717 | Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) | Week 28 | -6.2 Units on a scale | Standard Error 0.83 |
| TEV-50717 | Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) | Week 41 | -8.3 Units on a scale | Standard Error 0.97 |
| TEV-50717 | Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) | Week 54 | -6.5 Units on a scale | Standard Error 1.47 |
| TEV-50717 | Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) | Week 55 | -4.3 Units on a scale | Standard Error 1.6 |
Secondary
Change From Randomized Withdrawal Baseline (Week 28) in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) to Week 30
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.
Time frame: Week 28, Week 30
Population: All participants that completed Part 1, were randomized to Part 2, received at least one dose of study drug in the randomized withdrawal period and have an YGTSS TTS at both week 28 visit (randomized withdrawal baseline) and week 30 visit, and have a ≥25% reduction in the TTS from baseline in the parent study to week 28.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TEV-50717 | Change From Randomized Withdrawal Baseline (Week 28) in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) to Week 30 | 1.6 Units on a scale | Standard Error 0.86 |
| Randomized Placebo | Change From Randomized Withdrawal Baseline (Week 28) in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) to Week 30 | 2.0 Units on a scale | Standard Error 1.24 |
p-value: 0.7895% CI: [-3.4, 2.6]ANCOVA