Generalized Anxiety Disorder Proof of Concept Efficacy and Safety Study of SEP-225441 (Eszopiclone) In GAD Subjects

The HAM-A was administered by a site-trained rater and measured the severity of the subjects' anxiety symptoms using 14 items of the HAM-A rating scale. These items included: anxious mood, tension, fears, insomnia, intellectual, depressed mood, somatic complaints-muscular, somatic complaints-sensory, cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, genitourinary symptoms, autonomic symptoms, and behavior at interview. all items are measured on a 5-point scale (0-4). Ham-A total score can range from 0 to 56 with higher scores indicating higher severity of anxiety symptoms.

The HAM-A was administered by a site trained rater and measured the severity of the subjects' anxiety symptoms using 14 items of the HAM-A rating scale. These items include: anxious mood, tension, fears, insomnia, intellectual, depressed mood, somatic complaints-muscular, somatic complaints-sensory, cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, genitourinary symptoms, autonomic symptoms, and behavior at interview. All items are measured on a t5-point scale (0-4). Each HAM-A individual item score can range from 0 to 4 with higher scores indicating higher severity of anxiety questions.

The CGI-Swas completed by a board certified psychiatrist and represents the clinician's subjective assessment of severity of the subject's anxiety symptoms as assessed by a 7-scale score for a single question, "Considering your total clinical experience with this particular population, how anxious is the subject at this time?" The score was based on the following scale: 1=normal, not at all anxious; 2=borderline anxious; 3=mildly anxious; 4=moderately anxious; 5=markedly anxious; 6=severly anxious; 7=among the most extremely anxious subjects. CGI-S score can range from 0 to 7, with higher values indicating higher severity.

CGI-I was completed by a board certified psychiatrist and represented the clinician's subjective assessment of improvement of the subject's anxiety symptoms based on the following question, "Compared to his/her condition at Visit 2, how much has he/she changed?" The score was based on the following scale: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. CGI-I score can range from 0 to 7, with higher values indicating less improvement.

The HAM-A was administered by a site-trained rater and measured the severity of the subjects' anxiety symptoms using 14 items of the HAM-A rating scale. These items include: anxious mood, tension, fears, insomnia, intellectual, depressed mood, somatic complaints-muscular, somatic complaints-sensory, cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, genitourinary symptoms, autonomic symptoms, and behavior at interview. All items are measured on a 5-point scale (0-4). A 50% anxiolytic response was defined as a 50% or greater reduction from baseline in the HAM-A total score.

The Ham-A total score can range from 0 to 56 with higher scores indicating higher severity of anxiety symptoms.

The HAM-A was administered by a site-trained rater and measured the severity of the subjects' anxiety symptoms using 14 items of the HAM-A rating scale. These items include: anxious mood, tension, fears, insomnia, intellectual, depressed mood, somatic complaints-muscular, somatic complaints-sensory, cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, genitourinary symptoms, autonomic symptoms, and behavior at interview. All items are measured on a 5-point scale (0-4). Remission was defined as a HAM-A total score of 7 or less.

The Ham-A total score can range from 0 to 56 with higher scores indicating higher severity of anxiety symptoms.

The Q-LES-Q was completed by the subject and assessed quaility of life based on 16 items, each evaluated on a 5-point scale of overall level of enjoyment/satisfaction: 1=very poor; 2=poor; 3=fair; 4=good; 5=very good. The overall percentage score was computed as a sum of items 1 to 14 as expressed as a percentage of the maximum possible score: Overall Percentage Score = Sum [item 1... item 14]-14)/(70-14 ) *100%. Q-LES-Q overall percentage score can range from 0 to 100, with higher values indicating higher quality of life.

The ISI was completed by the subject and is an assessment of the severity of insomnia. The administered extended ISI questionnaire consists of 5 items (containing 7 questions, as item 1 contains 3 questions) comprising the original ISI questionnaire, plus 6 quality of life related items (sleep quality, restedness/refreshness upon arising, daytime fatigue, attention/concentration, relationships and mood disturbances), and 2 items assessing duration and frequency of sleep problems. All items, except for the insomnia duration and frequency questions, are measured on a Likert-type 5-point scale (0-4). ISI total score can range from 0 to 28, with higher scores indicating more severe insomnia.

The SDS was completed by the subject and captured the subject's level of disability. The subject rated the extent to which his or her work, social life or leisure activities, and home life or family responsibilities were impaired by his or her symptoms on a 10-point visual analog scale. SDS total score can range from 0 to 30, with higher scores indicating higher functional impairment.

ESS was completed by the subject and assessed daytime sedation based on 8 items, each presenting a situation for which the subject needed to evaluate how likely he/she is to doze off or fall asleep in contrast to feeling just tired. Each item was evaluated on the following scale: 0 = would never doze; 1 = slight chance of dozing; 2 = moderate chance of dozing; 3 = high chance of dozing. ESS total score can range from 0 to 24, with higher scores indicating higher levels of daytime sleepiness.