A Study to Examine the Efficacy of a Therapeutic THX-110 for Tourette Syndrome

Key secondary endpoint is the response to treatment according to YGTSS-TTS, defined as a reduction in YGTSS-TTS of at least 20% (compared to baseline) at week 12 of the double-blind phase (visit 9).

No. of Body Areas (score 0-4), Motor Tic Frequency (tics/min) (score 0-4) Phonic Tic Frequency (score 0-4) Severity of Motor Tics (score 0-4) Severity of Phonic Tics (score 0-4) Total score (0-20) 0=best, 20=worst

The CGI-S score obtained at the baseline (initiation) visit serves as a good basis for making this assessment. Only the following one query is rated on a seven-point scale: "Compared to the patient's condition at admission to the project [prior to medication initiation], this patient's condition is: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment."

The CGI-Severity (CGI-S) asks the clinician one question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients.

This rating is based upon observed and reported symptoms, behavior, and function in the past seven days. Clearly, symptoms and behavior can fluctuate over a week; the score should reflect the average severity level across the seven days.

The ATQ includes a list of 14 common motor tics and 131 common vocal tics. For each type of tic, participants are asked to indicate its presence during the past week by selecting "yes" or "no." Subsequently, for each tic endorsed, participants indicate its frequency and intensity, both on a 4-point Likert-type scale. For the frequency ratings, scores range from a few times a week or less (1), to constantly, almost all the time during the day (4). For the intensity ratings, participants are asked to check (1) if the specific tic was very mild in intensity in the past week, (2) or higher if the tic was obviously noticeable to others; and 3 or higher if the tic was much more forceful and very noticeable to others during the past week. A separate score of tic severity was calculated by summing the intensity and frequency score, resulting in a score between 2 (minimal frequency and intensity) to 8 (maximum frequency and intensity) for each tic endorsed.

HRQOL is often measured by four core questions that asked about general health status and number of unhealthy days in the Behavioral Risk Factor Surveillance System (BRFSS).

HrQoL in GTS patients is evaluated using the generic EQ-5D instrument (ref: EuroQol-Group. EQ-5D. Available at:www.euroqol.org. 2006.). It includes a five dimension descriptive system and a visual analog scale (EQVAS). The five dimensions include ''Mobility,'' ''Self-Care,'' ''Usual Activities,'' ''Pain/Discomfort,'' and ''Anxiety/Depression.'' All dimensions are subdivided into three levels (no problems, some problems, and extreme problems). Calculation of EQ-5D index score was performed using a regression algorithm generated by Greiner et al (ref: Greiner W, et al. The measurement and valuation of health status using EQ-5D: a European perspective. Dordrecht: Kluwer Academic Publisher; 2003.)

The PUTS is a 9-item self-report questionnaire measuring premonitory sensations in individuals with tics. Each item is scored from 1 (not at all true) to 4 (very much true). The total score is computed by summing the 9 items. Thus, total scores range from 9 to 36, and higher scores represent greater premonitory urges. The PUTS has demonstrated good internal consistency, test-retest reliability, and construct validity among youths between 11 and 16 years of age.The present manuscript reports the first psychometric data on the 9-item PUTS in an older adolescent and adult sample.

Add up the score for each of the twenty-one questions. The highest possible total for the whole test would be sixty-three. This would mean the number three was answered on all twenty-one questions. Since the lowest possible score for each question is zero, the lowest possible score for the test would be zero.

Total Score____________________Levels of Depression 1-10____________________These ups and downs are considered normal 11-16___________________ Mild mood disturbance 17-20___________________Borderline clinical depression 21-30___________________Moderate depression 31-40___________________Severe depression over 40__________________Extreme depression

The YBOCS is a 10-item clinician-rated measure of OCD symptom severity. Raters assess obsessions and compulsions separately in five domains: time spent, interference, distress, resistance, and control. Each domain is rated on a scale from 0 to 4. Thus, total scores range from 0 to 40, with higher scores indicating greater symptom severity.

The self-report and observer forms contain an identical set of scales, subscales, and indexes with a total of 30 items : Total ADHD symptoms: Inattentive (9 items), Hyperactive-Impulsive (9 items) subscales and ADHD Index (12 items) with each item rated on a 4-point scale (0=never, 1= a little, 2=often, 3= frequently) derived from from Conners' ADHD Rating Scale (CARS).

The total score is calculated by finding the sum of the 21 items. Score of 0-21 = low anxiety Score of 22-35 = moderate anxiety Score of 36 and above = potentially concerning levels of anxiety

The Pittsburgh Sleep Quality Index (PSQI) contains 19 self-rated questions and 5 questions rated by the bed partner or roommate (if one is available). Only self-rated questions are included in the scoring. The 19 self-rated items are combined to form seven "component" scores, each of which has a range of 0-3 points. In all cases, a score of "0" indicates no difficulty, while a score of "3" indicates severe difficulty. The seven component scores are then added to yield one "global" score, with a range of 0-21 points, "0" indicating no difficulty and "21 " indicating severe difficulties in all areas.

The SF-12 is a multipurpose short form survey with 12 questions, all selected from the SF-36 Health Survey. The questions were combined, scored, and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life.

Physical and Mental Health Composite Scores (PCS \& MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.