Study TV50717-CNS-30081 is a 55-week study in which participants who have successfully completed the parent study (Study TV50717-CNS-30080) may be eligible to enroll in this study. The primary objective of this study is to evaluate the safety and tolerability of long-term therapy with TEV-50717 in children and adolescents with DCP. The secondary objective of this study is to evaluate the efficacy of long-term therapy with TEV-50717 in reducing the severity of DCP.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
44
Oral tablets are 6, 9, and 12 mg.
Number of Participants With Adverse Events (AEs)
Adverse events can include any of the following: clinically significant vital signs, ECG parameters, or laboratory parameters. 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. SAEs included 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 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
Time frame: Baseline up to Week 55
Number of Participants (Aged ≥12 Years) With Columbia-Suicide Severity Rating Scale (C-SSRS) Outcomes (Worst Overall Finding)
Participants were placed into categories for suicidal ideation or behavior and non-suicidal self-injurious behavior based on their responses to various questions. For suicidal ideation or behavior, the following categories were used: None; Wish to be dead; Non-specific active suicidal thoughts; Any methods (not plan) without intent to act; Some intent to act, without specific plan; Specific plan and intent; Preparatory acts or behavior; Aborted attempt; Interrupted attempt; Actual attempt; and Suicide. For non-suicidal self-injurious behavior, the following categories were used: No or yes. Number of participants with worst overall finding of suicidal ideation or suicidal behavior and non-suicidal self-injurious behavior from Baseline to Week 54 are reported.
Time frame: Baseline to Week 54
Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) Subscale I Total Score at Week 54
The ESRS subscale I is a 7-item subjective questionnaire to evaluate parkinsonism, akathisia, dystonia and dyskinesia. The ESRS I is scored on a 4-point scale (0=absent, 1=Mild, 2=Moderate, 3=Severe) for each item. The evaluation takes into account the verbal report of the participant on 1) the frequency and duration of the symptom during the day, 2) the number of days the symptom was present during the last week, and 3) the subjective evaluation of the intensity of the symptom by the participant. Total score was the sum of the 7 items which ranges from 0 (absent) to 28 (severe). Higher scores indicate greater severity of disorder.
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Teva Investigational Site 14137
Birmingham, Alabama, United States
Teva Investigational Site 14295
San Diego, California, United States
Teva Investigational Site 14122
Voorhees Township, New Jersey, United States
Teva Investigational Site 14299
Charleston, South Carolina, United States
Teva Investigational Site 14129
Nashville, Tennessee, United States
Teva Investigational Site 39058
Blegdamsvej 9, Denmark
Teva Investigational Site 80146
Tel-Aviv, Tel-Aviv District, Israel
Teva Investigational Site 80147
Zerifin, Central District, Israel
Teva Investigational Site 30214
Milan, Italy
Teva Investigational Site 30216
Pisa, Italy
...and 20 more locations
Time frame: Baseline, Week 54
Change From Baseline in ESRS Subscale II Total Score at Week 54
The ESRS subscale II is a 17-item questionnaire to evaluate parkinsonism and akathisia. The ESRS II consists of the following parts: tremor (0 \[none\]-48 \[severe\]), gait and posture (0 \[none\]-6 \[severe\]), postural stability (0 \[none\]-6 \[severe\]), rigidity (0 \[none\]-24 \[severe\]), expressive automatic movements (0 \[none\]-6 \[severe\]), bradykinesia (0 \[none\]-6 \[severe\]), and akathisia (0 \[none\]-6 \[severe\]). Total score was the sum of the 17 items ranging from 0 (absent) to 102 (severe). Higher scores indicate greater severity of disorder.
Time frame: Baseline, Week 54
Change From Baseline in Child Behavior Checklist (CBCL) Competence Total Score at Week 53
The CBCL assesses behavioral and emotional status in children ages 6 through 18 years of age as reported by the caregiver. The full CBCL has two parts, a Competence Scale (Parts I to VII) and a Syndrome Scale (behavioral items). The Competence Scale (Parts I to VII) assesses various activities (for example, sports, hobbies, games, organizations, clubs, teams, groups, jobs, and chores), interpersonal relationships, and academic performance. The checklists having 120 questions consist of a number of statements about the child's behavior and responses which are recorded on a scale: 0 = Not True; 1 = Somewhat or Sometimes True; 2 = Very True or Often True. CBCL competence total score ranged from 0 (no problem) to 240 (lesser problem), which was calculated by adding individual scores of each domain. Higher scores indicate greater problems in child behavior.
Time frame: Baseline, Week 53
Change From Baseline in CBCL Syndrome Total Score at Week 53
The CBCL assesses behavioral and emotional status in children ages 6 through 18 years of age as reported by the caregiver. The full CBCL has two parts, a Competence Scale (Parts I to VII) and a Syndrome Scale (behavioral items). The Syndrome Scale comprises 113 questions related to problem behaviors. For each item, the responses are recorded on a scale: 0 = Not True; 1 = Somewhat or Sometimes True; 2 = Very True or Often True. The problem behaviors are scored on the following 8 empirically based syndromes: anxious/depressed, withdrawn/depressed, somatic complaints, social problems, thought problems, attention problems, rule-breaking behavior, and aggressive behavior. CBCL syndrome total score ranged from 0 (no problem) to 226 (lesser problem), which was calculated by adding individual scores of each domain. Higher scores indicate greater problems in child behavior.
Time frame: Baseline, Week 53
Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 54
The ESS is a self-administered questionnaire composed of 8 questions that provide a measure of a participant's general level of daytime sleepiness. The ESS is composed of 8 items. The responders were asked to rate their chances of falling asleep while engaged at 8 different activities, on a 4-point scale: 0 = would never fall asleep; 1=slight chance of falling asleep; 2=moderate chance of falling asleep; 3=high chance of falling asleep. Total score was calculated as the sum of 8 item scores ranging from 0 (never) to 24 (high chance of falling asleep). Higher scores indicate high chances of falling asleep.
Time frame: Baseline, Week 54
Change From Baseline in the Movement Disorder-Childhood Rating Scale (MD-CRS) Part I Total Score (General Assessment, Centrally Read)
The MD-CRS part I evaluates the impact of dyskinesia in cerebral palsy (DCP) on the activities of the participant and provides a general assessment of the movement disorder of motor function (7 items), oral/verbal function (3 items), self-care (3 items), and attention/alertness (2 items) on a scale of 0 (present) to 4 (absent). All items were scored by the rater in the clinic and were centrally read based on video recording. The total score was obtained by summing the individual items' scores and ranges from 0 (marked/prolonged disorder) to 60 (absent of a disorder), with higher scores indicating lesser disorder.
Time frame: Baseline, Week 53, Week 54
Change From Baseline in the MD-CRS Part II Total Score (Movement Disorder Severity, Centrally Read)
MD-CRS part II evaluates the severity of movement disorder on a scale of 0 to 4 in 7 body regions, all areas in which dyskinesia can be seen. All items were scored by the rater in the clinic and were centrally read based on video recording. In rating the movement disorder of a body part, 0 refers to absence of a movement disorder and 4 refers to a situation where movement disorder is present during all of the tasks for the region examined and/or involves 3 or more of the other regions, making completion impossible. The 7 body regions are (i) eye and periorbital region, (ii) face, (iii) tongue and perioral region, (iv) neck, (v) trunk, (vi) upper limb, and (vii) lower limb. Total score was obtained by summing the individual items scores and ranges from 0 (absent of a movement disorder) to 28 (marked/prolonged movement disorder), with higher scores indicating more movement disorder.
Time frame: Baseline, Week 53, Week 54
Change From Baseline in the MD-CRS Part I Total Score (General Assessment, Physician Rated)
The MD-CRS part I evaluates the impact of DCP on the activities of the participant and provides a general assessment of the movement disorder of motor function (7 items), oral/verbal function (3 items), self-care (3 items), and attention/alertness (2 items) on a scale of 0 (present) to 4 (absent). All items were scored by the investigational center physician. The total score was obtained by summing the individual items' scores and ranges from 0 (marked/prolonged movement disorder) to 60 (absent of a movement disorder), with higher scores indicating lesser movement disorder.
Time frame: Baseline, Week 53, Week 54
Change From Baseline in the MD-CRS Part II Total Score (General Assessment, Physician Rated)
The MD-CRS part II evaluates the severity of the movement disorder on a scale of 0 to 4 in 7 body regions, all areas in which dyskinesia can be seen in participants with CP. All items were scored by the investigational center physician. In rating the movement disorder of the body part, 0 refers to absence of a movement disorder and 4 refers to a situation where movement disorder is present during all of the tasks for the region examined and/or involves 3 or more of the other regions, making completion impossible. The 7 body regions are (i) eye and periorbital region, (ii) face, (iii) tongue and perioral region, (iv) neck, (v) trunk, (vi) upper limb, and (vii) lower limb. The total score was obtained by summing the individual items' scores and ranges from 0 (absent of a movement disorder) to 28 (marked/prolonged movement disorder), with higher scores indicating more movement disorder.
Time frame: Baseline, Week 53, Week 54
Change From Baseline in MD-CRS Global Index Score (Calculated From MD-CRS Parts I and II Total Scores, Physician Rated)
The MD-CRS Global Index is a global measure of the MD-CRS that consolidates the information from parts I and II using the method of weighted means of the 2 normalized indexes obtained from each part. The standardized/normalized score for each item of MD-CRS parts I and II with value X is calculated using the formula: Xst = X - Xmin divided by Xmax - Xmin, where Xmax is the maximum value for the score, and Xmin is the minimum value for the score, or 4 and 0 respectively. The normalized index for the scale, MD-CRS parts I or II, Index I or II, is calculated as the mean value of Xst. The MD-CRS Global Index is the weighted mean of the normalized indexes for centrally read MD-CRS parts I and II using the formula: Global index = n1 \* index 1 + n2 \* index 2 divided by n1 + n2, where n1 and n2 are the numbers of items in MD-CRS parts I and II respectively. The minimum score is 0 (better) and the maximum score is 1 (worse). The higher score indicates more severe movement disorder.
Time frame: Baseline, Week 53, Week 54
Change From Baseline in MD-CRS Global Index Score (Calculated From MD-CRS Parts I and II Total Scores, Centrally Read)
The MD-CRS Global Index is a global measure of the MD-CRS that consolidates the information from parts I and II using the method of weighted means of the 2 normalized indexes obtained from each part. The standardized/normalized score for each item of MD-CRS parts I and II with value X is calculated using the formula: Xst = X - Xmin divided by Xmax - Xmin, where Xmax is the maximum value for the score, and Xmin is the minimum value for the score, or 4 and 0 respectively. The normalized index for the scale, MD-CRS parts I or II, Index I or II, is calculated as the mean value of Xst. The MD-CRS Global Index is the weighted mean of the normalized indexes for centrally read MD-CRS parts I and II using the formula: Global index = n1 \* index 1 + n2 \* index 2 divided by n1 + n2, where n1 and n2 are the numbers of items in MD-CRS parts I and II respectively. The minimum score is 0 (better) and the maximum score is 1 (worse). The higher score indicates more severe movement disorder.
Time frame: Baseline, Week 53, Week 54
Change From Baseline in Caregiver Global Impression of Improvement (CaGI-I) Scale Score (Global, Caregiver Rated) at Week 54
The CaGI-I is single item questionnaire to assess the caregiver's impression of improvement in dyskinesia symptoms after initiating therapy. The scale is a caregiver-reported outcome that aims to evaluate all aspects of participants' health and determine if there has been an overall improvement or not in dyskinesia symptoms. The caregiver selected the 1 response from the response options that gave the most accurate description of change in dyskinesia symptoms of the participant they cared for from the beginning of the study: 1=very much improved (since the initiation of treatment); 2=much improved; 3=minimally improved; 4=no change from baseline (symptoms remain essentially unchanged); 5=minimally worse; 6=much worse; 7=very much worse (since the initiation of treatment). The change from baseline CaGI-I score can range from -6 to 6.
Time frame: Baseline, Week 54
Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Scale Score (Global, Physician Rated) at Week 54
CGI-I is a clinician-reported outcome with a 7-point Likert scale to compare participant's condition to the baseline condition: 1=very much improved since initiation of treatment (nearly all better; good level of functioning; minimal symptoms; represents a very substantial change); 2=much improved (notably better with significant reduction of symptoms; increase in level of functioning but some symptoms remain); 3=minimally improved (slightly better with little or no clinically meaningful reduction of symptoms; represents very little change in basic clinical status, level of care, or functional capacity); 4=no change from baseline (symptoms remain unchanged); 5=minimally worse (slightly worse but may not be clinically meaningful); 6=much worse (clinically significant increase in symptoms and diminished functioning); 7=very much worse since initiation of treatment (severe exacerbation of symptoms and loss of functioning). The change from baseline CGI-I score can range from -6 to 6.
Time frame: Baseline, Week 54
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Scale Score (Global, Physician Rated) at Week 54
The CGI-S uses a 7-point Likert scale to assess dyskinesia severity as follows (with anchor points for choosing the most appropriate severity level caused by DCP): 1=normal (not at all ill, symptoms of disorder not present past 7 days); 2=borderline (subtle or suspected pathology); 3=mild (clearly established symptoms with minimal, if any, distress or difficulty in social and/or occupational function); 4=moderate (overt symptoms causing noticeable, but modest, functional impairment or distress; symptom level may warrant medication); 5=marked (intrusive symptoms that distinctly impair social/occupational function or cause intrusive levels of distress); 6=severe (disruptive symptoms, behavior, and function are frequently influenced by symptoms, may require assistance from others); 7=extreme (symptoms drastically interfere in many life functions; may be hospitalized). Higher scores indicating more severity.
Time frame: Baseline, Week 54
Change From Baseline in Pediatric Evaluation Disability Inventory-Computer Adapted Test (PEDI-CAT) Score (Activities of Daily Living [ADL], Caregiver Completed, Content-Balanced Version) at Week 53
The PEDI-CAT measures function in 4 domains: (1) Daily Activities; (2) Mobility; (3) Social/Cognitive, and (4) Responsibility. The content-balanced version presents a balance of items from each of the Daily Activities domain's content areas (Getting Dressed, Keeping Clean, Home Tasks, and Eating and Mealtime). A total of approximately 30 items were administered. PEDI-CAT software utilizes Item Response Theory statistical models to estimate a child's abilities from a minimal number of the most relevant items or from a set number of items within each domain. The CAT program then displays the results: normative standard scores, scaled scores, and SE. Scaled score is reported in this endpoint. Scaled scores are based on an estimate of the placement of an individual child along the hierarchical scale within each domain. PEDI-CAT scaled scores are currently on a 20 (lesser improvement) to 80 (more improvement) scale metric. Higher scores indicate greater improvement in functional skills.
Time frame: Baseline, Week 53
Change From Baseline in Unified Huntington's Disease Rating Scale-Total Maximal Chorea (UHDRS-TMC) Score (Centrally Read) at Week 53
The UHDRS-TMC is part of the Unified Huntington's Disease Rating Scale-Total Motor Score (UHDRS-TMS) assessment and assesses the severity of chorea in the 7 body parts: face, mouth, trunk, and the 4 extremities (right and left upper extremities, right and left lower extremities). Each part was rated from 0 (absent) to 4 (prolonged). The central rating was done for all participants, based on the videos collected for the central rating of MD-CRS. The TMC score was obtained by adding up each of the separate scores and ranged from 0 (absent) to 28 (marked/prolonged), with higher scores indicating the worse symptoms.
Time frame: Baseline, Week 53
Change From Baseline in Unified Huntington's Disease Rating Scale-Total Maximal Dystonia (UHDRS-TMD) Score (Centrally Read) at Week 53
The UHDRS-TMD is part of the UHDRS-TMS assessment and assesses the severity of dystonia in the 5 body parts: trunk and the 4 extremities (right and left upper extremities, right and left lower extremities). Each part was rated from 0 (absent) to 4 (prolonged). The central rating was done for all participants, based on the videos collected for the central rating of MD-CRS. The TMD score was obtained by adding up each of the separate scores and ranged from 0 (absent) to 20 (marked/prolonged), with higher scores indicating the worse symptoms.
Time frame: Baseline, Week 53
Change From Baseline in Unified Huntington's Disease Rating Scale-Total Motor Score (UHDRS-TMS) Score (Physician Rated) at Week 53
The UHDRS comprises a broad assessment of features associated with Huntington's disease (HD). It is a research tool that has been developed to provide a uniform assessment of the clinical features and course of HD. The Total Motor Score assessment of the UHDRS (UHDRS-TMS) comprises 15 items and assesses eye movements, speech, alternating hand movements, dystonia, chorea, and gait. The UHDRS-TMS was calculated as the sum of the 31 motor assessments; each of which ranged between 0 (absent) to 4 (worst). All items were scored by the investigational center physician. TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function), with lower scores indicating better motor function.
Time frame: Baseline, Week 53
Change From Baseline in Unified Huntington's Disease Rating Scale-Total Maximal Chorea (UHDRS-TMC) Score (Physician Rated) at Week 53
The UHDRS-TMC is part of the UHDRS-TMS assessment and assesses the severity of chorea in the 7 body parts: face, mouth, trunk, and the 4 extremities (right and left upper extremities, right and left lower extremities). Each part was rated from 0 (absent) to 4 (prolonged). All items were scored by the investigational center physician. The TMC score was obtained by adding up each of the separate scores and ranged from 0 (absent) to 28 (marked/prolonged), with higher scores indicating the worse symptoms.
Time frame: Baseline, Week 53
Change From Baseline in Unified Huntington's Disease Rating Scale-Total Maximal Dystonia (UHDRS-TMD) Score (Physician Rated) at Week 53
The UHDRS-TMD is part of the UHDRS-TMS assessment and assesses the severity of dystonia in the 5 body parts: trunk and the 4 extremities (right and left upper extremities, right and left lower extremities). Each part was rated from 0 (absent) to 4 (prolonged). All items were scored by the investigational center physician. The TMD score was obtained by adding up each of the separate scores and ranged from 0 (absent) to 20 (marked/prolonged), with higher scores indicating the worse symptoms.
Time frame: Baseline, Week 53
Change From Baseline in Canadian Occupational Performance Measure (COPM) (Physician Rated) Score at Week 53
The COPM, a semi-structured interview, was used to assess a participant's perception of performance in the areas of self-care, productivity and leisure. The COPM involves a 5-step process within a semi-structured interview conducted by a therapist. The participants were asked to rate 5 most important activities on a 10-point scale for performance and satisfaction, ranging from 1 (not at all able/satisfied) to 10 (able to perform extremely well/ extremely satisfied). Total score is the average of the total performance and satisfaction subscales. Each subscale score is calculated by adding the scores of all activities and then dividing by the number of the activities. The total change from baseline scores can range from -9 to 9. Higher scores indicated very good performance and high satisfaction.
Time frame: Baseline, Week 53