Trial Outcomes & Findings for Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents (NCT NCT03567291)
NCT ID: NCT03567291
Last Updated: 2021-11-09
Results Overview
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.
TERMINATED
PHASE3
228 participants
Day 1 to Week 55
2021-11-09
Participant Flow
228 participants with Tourette Syndrome were enrolled after completing one of two eligible parent studies.
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.
Participant milestones
| Measure |
TEV-50717
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.
|
Randomized TEV-50717
Participants were randomized to their current dose of TEV-50717, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period.
|
Randomized Placebo
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
TEV-50717 Re-titration and Maintenance
Participants who were randomized to placebo during the withdrawal period were re-titrated to their TEV-50717 maintenance dose. Participants who were randomized to TEV-50717 continued their maintenance dose.
|
|---|---|---|---|---|
|
Period I
STARTED
|
228
|
0
|
0
|
0
|
|
Period I
Safety Set
|
227
|
0
|
0
|
0
|
|
Period I
Intent to Treat Set
|
228
|
0
|
0
|
0
|
|
Period I
COMPLETED
|
137
|
0
|
0
|
0
|
|
Period I
NOT COMPLETED
|
91
|
0
|
0
|
0
|
|
Period II
STARTED
|
0
|
91
|
46
|
0
|
|
Period II
COMPLETED
|
0
|
88
|
45
|
0
|
|
Period II
NOT COMPLETED
|
0
|
3
|
1
|
0
|
|
Period III
STARTED
|
0
|
0
|
0
|
133
|
|
Period III
COMPLETED
|
0
|
0
|
0
|
48
|
|
Period III
NOT COMPLETED
|
0
|
0
|
0
|
85
|
Reasons for withdrawal
| Measure |
TEV-50717
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.
|
Randomized TEV-50717
Participants were randomized to their current dose of TEV-50717, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period.
|
Randomized Placebo
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
TEV-50717 Re-titration and Maintenance
Participants who were randomized to placebo during the withdrawal period were re-titrated to their TEV-50717 maintenance dose. Participants who were randomized to TEV-50717 continued their maintenance dose.
|
|---|---|---|---|---|
|
Period I
Adverse Event
|
14
|
0
|
0
|
0
|
|
Period I
Protocol Violation
|
1
|
0
|
0
|
0
|
|
Period I
Withdrawal by Subject
|
23
|
0
|
0
|
0
|
|
Period I
Lost to Follow-up
|
2
|
0
|
0
|
0
|
|
Period I
Terminated by sponsor
|
44
|
0
|
0
|
0
|
|
Period I
Missing or unknown
|
7
|
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
Withdrawal by Subject
|
0
|
0
|
0
|
4
|
|
Period III
Lost to Follow-up
|
0
|
0
|
0
|
1
|
|
Period III
Terminated by sponsor
|
0
|
0
|
0
|
68
|
|
Period III
Missing or unknown
|
0
|
0
|
0
|
8
|
Baseline Characteristics
Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
Baseline characteristics by cohort
| Measure |
All Participants
n=228 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.
|
|---|---|
|
Age, Continuous
|
12 Years
STANDARD_DEVIATION 2.59 • n=113 Participants
|
|
Sex/Gender, Customized
Participants · Male
|
182 Participants
n=113 Participants
|
|
Sex/Gender, Customized
Participants · Female
|
45 Participants
n=113 Participants
|
|
Sex/Gender, Customized
Participants · Unknown
|
1 Participants
n=113 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
38 Participants
n=113 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
186 Participants
n=113 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=113 Participants
|
|
Race/Ethnicity, Customized
White
|
197 Participants
n=113 Participants
|
|
Race/Ethnicity, Customized
Black
|
4 Participants
n=113 Participants
|
|
Race/Ethnicity, Customized
Asian
|
7 Participants
n=113 Participants
|
|
Race/Ethnicity, Customized
Native American
|
5 Participants
n=113 Participants
|
|
Race/Ethnicity, Customized
Other
|
15 Participants
n=113 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Week 55Population: Safety analysis set included all participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
TEV-50717
n=227 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.
|
Randomized Placebo
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
|---|---|---|
|
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined
At least one adverse event leading to withdrawal
|
14 Participants
|
—
|
|
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined
At least one adverse event
|
161 Participants
|
—
|
|
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined
At least one serious adverse event
|
2 Participants
|
—
|
|
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined
At least one severe adverse event
|
6 Participants
|
—
|
|
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined
At least one AE related to investigational product
|
95 Participants
|
—
|
PRIMARY outcome
Timeframe: Weeks 28 to 30Population: 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).
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.
Outcome measures
| Measure |
TEV-50717
n=84 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.
|
Randomized Placebo
n=42 Participants
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
|---|---|---|
|
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II)
At least one adverse event
|
16 Participants
|
6 Participants
|
|
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II)
At least one serious adverse event
|
0 Participants
|
0 Participants
|
|
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II)
At least one AE related to investigational product
|
6 Participants
|
1 Participants
|
|
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II)
At least one adverse event leading to withdrawal
|
0 Participants
|
0 Participants
|
|
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II)
At least one severe adverse event
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for specified categories.
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.
Outcome measures
| Measure |
TEV-50717
n=227 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.
|
Randomized Placebo
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
|---|---|---|
|
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
|
—
|
|
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 5.0
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for specified categories.
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.
Outcome measures
| Measure |
TEV-50717
n=227 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.
|
Randomized Placebo
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Week 28, Week 30Population: 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.
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.
Outcome measures
| Measure |
TEV-50717
n=83 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.
|
Randomized Placebo
n=41 Participants
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
|---|---|---|
|
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
|
0.6 Units On A Scale
Standard Deviation 3.62
|
PRIMARY outcome
Timeframe: Week 28, Week 30Population: 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.
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.
Outcome measures
| Measure |
TEV-50717
n=82 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.
|
Randomized Placebo
n=39 Participants
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
|---|---|---|
|
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 3.30
|
-0.6 Units On A Scale
Standard Deviation 3.08
|
PRIMARY outcome
Timeframe: Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable at specified timepoints.
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.
Outcome measures
| Measure |
TEV-50717
n=227 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.
|
Randomized Placebo
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
|---|---|---|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 4
|
2 Participants
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 34
|
0 Participants
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 41
|
1 Participants
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 54
|
0 Participants
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 55
|
0 Participants
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Baseline
|
0 Participants
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 2
|
0 Participants
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 8
|
0 Participants
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 15
|
1 Participants
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 28
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Week 28, Week 30Population: 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.
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.
Outcome measures
| Measure |
TEV-50717
n=84 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.
|
Randomized Placebo
n=42 Participants
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
|---|---|---|
|
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
|
0 Participants
|
|
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
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 15, 28, 41, 54, and 55Population: ITT analysis set includes all participants enrolled in part I. Here, 'number analyzed' signifies participants evaluable at specified time points.
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.
Outcome measures
| Measure |
TEV-50717
n=228 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.
|
Randomized Placebo
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Baseline, Weeks 8, 15, 28, 41, 54, and 55Population: 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.
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.
Outcome measures
| Measure |
TEV-50717
n=228 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.
|
Randomized Placebo
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 15, 28, 41, 54, and 55Population: 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.
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.
Outcome measures
| Measure |
TEV-50717
n=228 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.
|
Randomized Placebo
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Baseline, Weeks 6, 28, 34, 54Population: 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.
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.
Outcome measures
| Measure |
TEV-50717
n=228 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.
|
Randomized Placebo
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
SECONDARY outcome
Timeframe: Week 28, Week 30Population: 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.
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.
Outcome measures
| Measure |
TEV-50717
n=54 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.
|
Randomized Placebo
n=26 Participants
Participants were randomized to placebo, which was administered during the Part B Randomized Drug Withdrawal (RW) 2-week period only.
|
|---|---|---|
|
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
|
2.0 Units on a scale
Standard Error 1.24
|
Adverse Events
Total
Serious adverse events
| Measure |
Total
n=227 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.44%
1/227 • Number of events 1 • Baseline to Week 55
Adverse events were analyzed for participants in Parts A \& B combined as one group per planned analysis. Safety analysis set included all participants who received at least 1 dose of study drug.
|
|
Psychiatric disorders
Self-injurious ideation
|
0.44%
1/227 • Number of events 1 • Baseline to Week 55
Adverse events were analyzed for participants in Parts A \& B combined as one group per planned analysis. Safety analysis set included all participants who received at least 1 dose of study drug.
|
Other adverse events
| Measure |
Total
n=227 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Vomiting
|
6.6%
15/227 • Number of events 30 • Baseline to Week 55
Adverse events were analyzed for participants in Parts A \& B combined as one group per planned analysis. Safety analysis set included all participants who received at least 1 dose of study drug.
|
|
General disorders
Pyrexia
|
5.7%
13/227 • Number of events 13 • Baseline to Week 55
Adverse events were analyzed for participants in Parts A \& B combined as one group per planned analysis. Safety analysis set included all participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
10.1%
23/227 • Number of events 33 • Baseline to Week 55
Adverse events were analyzed for participants in Parts A \& B combined as one group per planned analysis. Safety analysis set included all participants who received at least 1 dose of study drug.
|
|
Investigations
Weight increased
|
9.7%
22/227 • Number of events 22 • Baseline to Week 55
Adverse events were analyzed for participants in Parts A \& B combined as one group per planned analysis. Safety analysis set included all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
13.2%
30/227 • Number of events 55 • Baseline to Week 55
Adverse events were analyzed for participants in Parts A \& B combined as one group per planned analysis. Safety analysis set included all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Somnolence
|
12.3%
28/227 • Number of events 33 • Baseline to Week 55
Adverse events were analyzed for participants in Parts A \& B combined as one group per planned analysis. Safety analysis set included all participants who received at least 1 dose of study drug.
|
|
Psychiatric disorders
Anxiety
|
7.5%
17/227 • Number of events 18 • Baseline to Week 55
Adverse events were analyzed for participants in Parts A \& B combined as one group per planned analysis. Safety analysis set included all participants who received at least 1 dose of study drug.
|
|
Psychiatric disorders
Tic
|
6.6%
15/227 • Number of events 29 • Baseline to Week 55
Adverse events were analyzed for participants in Parts A \& B combined as one group per planned analysis. Safety analysis set included all participants who received at least 1 dose of study drug.
|
Additional Information
Director, Clinical Research
Teva Branded Pharmaceutical Products R&D, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
- Publication restrictions are in place
Restriction type: OTHER