A Study to Test if TEV-50717 is Safe and Effective in Relieving Abnormal Involuntary Movements in Cerebral Palsy

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.