Trial Outcomes & Findings for Generalized Anxiety Disorder Proof of Concept Efficacy and Safety Study of SEP-225441 (Eszopiclone) In GAD Subjects (NCT NCT00616655)

NCT ID: NCT00616655

Last Updated: 2016-04-08

Results Overview

THe HAM-M was administered by a site-trained rater and measured the severity of the subjects' anxiety symptoms using 14 items of the HAM-M 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). The Ham-A total score can range from 0 to 56 with higher scores indicating higher severity of anxiety symptoms.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

456 participants

Primary outcome timeframe

Baseline to Week 8

Results posted on

2016-04-08

Participant Flow

Participant milestones

Participant milestones
Measure
Placebo Arm
Placebo
Eszopiclone Low Dose Arm
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Overall Study
STARTED
152
153
151
Overall Study
COMPLETED
117
112
103
Overall Study
NOT COMPLETED
35
41
48

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo Arm
Placebo
Eszopiclone Low Dose Arm
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Overall Study
Adverse Event
10
7
12
Overall Study
Lack of Efficacy
5
5
5
Overall Study
Lost to Follow-up
3
12
10
Overall Study
Protocol Violation
2
4
3
Overall Study
Withdrawal by Subject
9
7
11
Overall Study
Does not meet in/ex criteria
0
0
2
Overall Study
Other
6
6
5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo Arm
n=149 Participants
Placebo
Eszopiclone Low Dose Arm
n=146 Participants
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 Participants
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Total
n=440 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Age, Categorical
Between 18 and 65 years
149 Participants
n=5 Participants
146 Participants
n=7 Participants
145 Participants
n=5 Participants
440 Participants
n=4 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Sex: Female, Male
Female
111 Participants
n=5 Participants
108 Participants
n=7 Participants
102 Participants
n=5 Participants
321 Participants
n=4 Participants
Sex: Female, Male
Male
38 Participants
n=5 Participants
38 Participants
n=7 Participants
43 Participants
n=5 Participants
119 Participants
n=4 Participants
Region of Enrollment
United States
149 participants
n=5 Participants
146 participants
n=7 Participants
145 participants
n=5 Participants
440 participants
n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Week 8

Population: ITT Population: /The ITT population will include all randomized subjects who received at least one does of study medication during the double-blind period.

THe HAM-M was administered by a site-trained rater and measured the severity of the subjects' anxiety symptoms using 14 items of the HAM-M 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). The Ham-A total score can range from 0 to 56 with higher scores indicating higher severity of anxiety symptoms.

Outcome measures

Outcome measures
Measure
Placebo Arm
n=149 Participants
Placebo
Eszopiclone Low Dose Arm
n=146 Participants
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 Participants
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Change From Baseline to Week 8 in the Total Score on the Hamilton Anxiety Scale (HAM-A), as Assessed by the Site-trained Rater
-10.0 Units on a scale
Standard Deviation 7.0
-9.3 Units on a scale
Standard Deviation 7.4
-9.5 Units on a scale
Standard Deviation 8.1

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6 based on last observation carried forward (LOCF)

Population: ITT Population: The ITT population will include all randomized subjects who received at least one dose of study medication during the double-blind period.

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.

Outcome measures

Outcome measures
Measure
Placebo Arm
n=149 Participants
Placebo
Eszopiclone Low Dose Arm
n=146 Participants
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 Participants
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Change From Baseline Hamilton Anxiety Scale (HAM-A) Total Score (Except for Week 8)
Week 4-Change from baseline
-8.1 unit on a scale
Standard Deviation 6.0
-7.6 unit on a scale
Standard Deviation 6.3
-8.0 unit on a scale
Standard Deviation 6.8
Change From Baseline Hamilton Anxiety Scale (HAM-A) Total Score (Except for Week 8)
Week 6- Change from baseline
-8.9 unit on a scale
Standard Deviation 6.3
-8.7 unit on a scale
Standard Deviation 7.2
-8.5 unit on a scale
Standard Deviation 7.4
Change From Baseline Hamilton Anxiety Scale (HAM-A) Total Score (Except for Week 8)
Baseline
24.2 unit on a scale
Standard Deviation 3.4
24.0 unit on a scale
Standard Deviation 3.4
24.0 unit on a scale
Standard Deviation 3.7
Change From Baseline Hamilton Anxiety Scale (HAM-A) Total Score (Except for Week 8)
Week 2 - Change from baseline
-5.7 unit on a scale
Standard Deviation 5.7
-4.8 unit on a scale
Standard Deviation 5.0
-6.0 unit on a scale
Standard Deviation 6.1

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8

Population: ITT Population: The ITT population will include all randomized subjects who received at least one dose of study medication during the double-blind period.

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.

Outcome measures

Outcome measures
Measure
Placebo Arm
n=149 Participants
Placebo
Eszopiclone Low Dose Arm
n=146 Participants
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 Participants
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Change in Individual Item Scores on HAM-A
Respiratory Symptoms-Baseline
1.2 units on a scale
Standard Deviation 0.9
1.2 units on a scale
Standard Deviation 0.9
1.3 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Anxious Mood-Baseline
2.8 units on a scale
Standard Deviation 0.5
2.8 units on a scale
Standard Deviation 0.5
2.8 units on a scale
Standard Deviation 0.5
Change in Individual Item Scores on HAM-A
Tension - Week 4 - Change from baseline
-0.8 units on a scale
Standard Deviation 1.0
-0.6 units on a scale
Standard Deviation 0.9
-0.8 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Fears- Week 4- Change from baseline
-0.4 units on a scale
Standard Deviation 0.9
-0.5 units on a scale
Standard Deviation 0.9
-0.3 units on a scale
Standard Deviation 0.8
Change in Individual Item Scores on HAM-A
Intellectual- Week 2- Change from baseline
-0.4 units on a scale
Standard Deviation 0.9
-0.4 units on a scale
Standard Deviation 0.9
-0.5 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Depressed Mood- Baseline
1.1 units on a scale
Standard Deviation 0.8
1.2 units on a scale
Standard Deviation 0.7
1.0 units on a scale
Standard Deviation 0.7
Change in Individual Item Scores on HAM-A
Depressed Mood- Week 2- Change from baseline
-0.3 units on a scale
Standard Deviation 0.8
-0.2 units on a scale
Standard Deviation 0.8
-0.2 units on a scale
Standard Deviation 0.8
Change in Individual Item Scores on HAM-A
Somatic Complaints-Sensory-Baseline
1.0 units on a scale
Standard Deviation 0.9
1.0 units on a scale
Standard Deviation 0.9
1.2 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Respiratory Symptoms-Wk 2 Change from baseline
-0.4 units on a scale
Standard Deviation 0.9
-0.3 units on a scale
Standard Deviation 0.8
-0.4 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Respiratory Symptoms-Wk 8 Change from baseline
-0.6 units on a scale
Standard Deviation 0.9
-0.6 units on a scale
Standard Deviation 0.9
-0.7 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Gastrointestinal Symptoms- Baseline
1.4 units on a scale
Standard Deviation 1.0
1.4 units on a scale
Standard Deviation 1.0
1.3 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Genitourinary Symptoms-Wk 2-Change from baseline
-0.4 units on a scale
Standard Deviation 1.0
-0.2 units on a scale
Standard Deviation 1.0
-0.3 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Genitourinary Symptoms-Wk 8-Change from baseline
-0.6 units on a scale
Standard Deviation 1.1
-0.5 units on a scale
Standard Deviation 1.1
-0.4 units on a scale
Standard Deviation 1.1
Change in Individual Item Scores on HAM-A
Autonomic Symptoms-Wk 2-Change from baseline
-0.4 units on a scale
Standard Deviation 0.9
-0.3 units on a scale
Standard Deviation 0.9
-0.4 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Autonomic Symptoms-Wk 4-Change from baseline
-0.5 units on a scale
Standard Deviation 1.0
-0.5 units on a scale
Standard Deviation 1.2
-0.5 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Behavior at Interview-Wk 2- Change from baseline
-0.4 units on a scale
Standard Deviation 0.8
-0.3 units on a scale
Standard Deviation 0.7
-0.4 units on a scale
Standard Deviation 0.8
Change in Individual Item Scores on HAM-A
Behavior at Interview-Wk 4- Change from baseline
-0.6 units on a scale
Standard Deviation 0.7
-0.6 units on a scale
Standard Deviation 0.8
-0.5 units on a scale
Standard Deviation 0.7
Change in Individual Item Scores on HAM-A
Behavior at Interview-Wk 8- Change from baseline
-0.8 units on a scale
Standard Deviation 0.8
-0.6 units on a scale
Standard Deviation 0.9
-0.7 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Respiratory Symptoms-Wk 4 Change from baseline
-0.5 units on a scale
Standard Deviation 0.9
-0.5 units on a scale
Standard Deviation 0.9
-0.5 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Respiratory Symptoms-Wk 6 Change from baseline
-0.6 units on a scale
Standard Deviation 0.9
-0.5 units on a scale
Standard Deviation 1.0
-0.5 units on a scale
Standard Deviation 1.1
Change in Individual Item Scores on HAM-A
Gastrointestinal Symptoms-Wk2-Change from baseline
-0.3 units on a scale
Standard Deviation 1.1
-0.4 units on a scale
Standard Deviation 1.0
-0.3 units on a scale
Standard Deviation 1.1
Change in Individual Item Scores on HAM-A
Gastrointestinal Symptoms-Wk4-Change from baseline
-0.5 units on a scale
Standard Deviation 1.0
-0.5 units on a scale
Standard Deviation 1.0
-0.4 units on a scale
Standard Deviation 1.1
Change in Individual Item Scores on HAM-A
Gastrointestinal Symptoms-Wk6-Change from baseline
-0.6 units on a scale
Standard Deviation 1.0
-0.6 units on a scale
Standard Deviation 1.0
-0.5 units on a scale
Standard Deviation 1.1
Change in Individual Item Scores on HAM-A
Gastrointestinal Symptoms-Wk8-Change from baseline
-0.6 units on a scale
Standard Deviation 1.0
-0.6 units on a scale
Standard Deviation 1.0
-0.5 units on a scale
Standard Deviation 1.1
Change in Individual Item Scores on HAM-A
Genitourinary Symptoms-Baseline
1.5 units on a scale
Standard Deviation 1.0
1.4 units on a scale
Standard Deviation 1.0
1.4 units on a scale
Standard Deviation 1.1
Change in Individual Item Scores on HAM-A
Genitourinary Symptoms-Wk 4-Change from baseline
-0.4 units on a scale
Standard Deviation 1.1
-0.4 units on a scale
Standard Deviation 1.1
-0.4 units on a scale
Standard Deviation 1.1
Change in Individual Item Scores on HAM-A
Genitourinary Symptoms-Wk 6-Change from baseline
-0.5 units on a scale
Standard Deviation 1.1
-0.4 units on a scale
Standard Deviation 1.1
-0.3 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Autonomic Symptoms-Baseline
1.8 units on a scale
Standard Deviation 0.9
1.8 units on a scale
Standard Deviation 0.8
1.8 units on a scale
Standard Deviation 0.8
Change in Individual Item Scores on HAM-A
Autonomic Symptoms-Wk 6-Change from baseline
-0.6 units on a scale
Standard Deviation 1.0
-0.6 units on a scale
Standard Deviation 1.1
-0.6 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Autonomic Symptoms-Wk 8-Change from baseline
-0.8 units on a scale
Standard Deviation 1.1
-0.7 units on a scale
Standard Deviation 1.2
-0.6 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Behavior at Interview-Baseline
1.8 units on a scale
Standard Deviation 0.7
1.8 units on a scale
Standard Deviation 0.6
1.8 units on a scale
Standard Deviation 0.6
Change in Individual Item Scores on HAM-A
Behavior at Interview-Wk 6- Change from baseline
-0.7 units on a scale
Standard Deviation 0.8
-0.7 units on a scale
Standard Deviation 0.8
-0.7 units on a scale
Standard Deviation 0.8
Change in Individual Item Scores on HAM-A
Fears- Week 2- Change from baseline
-0.3 units on a scale
Standard Deviation 0.9
-0.4 units on a scale
Standard Deviation 0.8
-0.2 units on a scale
Standard Deviation 0.8
Change in Individual Item Scores on HAM-A
Anxious Mood-Week 2 -Change from baseline
-0.6 units on a scale
Standard Deviation 0.8
-0.5 units on a scale
Standard Deviation 0.7
-0.6 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Anxious Mood-Week 4 - Change from baseline
-0.8 units on a scale
Standard Deviation 0.9
-0.8 units on a scale
Standard Deviation 0.8
-0.9 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Anxious Mood-Week 6 - Change from baseline
-1.0 units on a scale
Standard Deviation 0.9
-0.8 units on a scale
Standard Deviation 0.8
-1.0 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Anxious Mood-Week 8- Change from baseline
-1.0 units on a scale
Standard Deviation 1.0
-0.9 units on a scale
Standard Deviation 0.9
-1.1 units on a scale
Standard Deviation 1.1
Change in Individual Item Scores on HAM-A
Tension - Baseline
2.7 units on a scale
Standard Deviation 0.5
2.6 units on a scale
Standard Deviation 0.5
2.7 units on a scale
Standard Deviation 0.5
Change in Individual Item Scores on HAM-A
Tension - Week 2 -Change from baseline
-0.5 units on a scale
Standard Deviation 0.9
-0.4 units on a scale
Standard Deviation 0.7
-0.6 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Tension - Week 6- Change from baseline
-0.9 units on a scale
Standard Deviation 1.0
-0.8 units on a scale
Standard Deviation 1.0
-1.0 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Tension - Week 8- Change from baseline
-0.9 units on a scale
Standard Deviation 1.0
-0.9 units on a scale
Standard Deviation 1.0
-1.0 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Fears- Baseline
1.1 units on a scale
Standard Deviation 1.1
1.2 units on a scale
Standard Deviation 1.0
1.0 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Fears- Week 6- Change from baseline
-0.4 units on a scale
Standard Deviation 1.0
-0.5 units on a scale
Standard Deviation 0.9
-0.4 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Fears- Week 8- Change from baseline
-0.5 units on a scale
Standard Deviation 0.9
-0.7 units on a scale
Standard Deviation 1.0
-0.4 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Insomnia- Baseline
2.5 units on a scale
Standard Deviation 0.7
2.5 units on a scale
Standard Deviation 0.7
2.6 units on a scale
Standard Deviation 0.8
Change in Individual Item Scores on HAM-A
Insomnia- Week 2- Change from baseline
-0.5 units on a scale
Standard Deviation 0.9
-0.5 units on a scale
Standard Deviation 1.0
-0.8 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Insomnia- Week 4- Change from baseline
-0.8 units on a scale
Standard Deviation 1.1
-0.8 units on a scale
Standard Deviation 1.0
-0.9 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Insomnia- Week 6- Change from baseline
-0.8 units on a scale
Standard Deviation 1.0
-0.8 units on a scale
Standard Deviation 1.0
-0.9 units on a scale
Standard Deviation 1.1
Change in Individual Item Scores on HAM-A
insomnia- Week 8- Change from baseline
-0.9 units on a scale
Standard Deviation 1.1
-0.8 units on a scale
Standard Deviation 1.0
-1.0 units on a scale
Standard Deviation 1.2
Change in Individual Item Scores on HAM-A
Intellectual- Baseline
2.1 units on a scale
Standard Deviation 0.8
2.1 units on a scale
Standard Deviation 0.8
2.2 units on a scale
Standard Deviation 0.8
Change in Individual Item Scores on HAM-A
Intellectual- Week 4- Change from baseline
-0.8 units on a scale
Standard Deviation 1.0
-0.6 units on a scale
Standard Deviation 0.9
-0.7 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Intellectual- Week 6- Change from baseline
-0.7 units on a scale
Standard Deviation 1.1
-0.7 units on a scale
Standard Deviation 1.0
-0.8 units on a scale
Standard Deviation 1.1
Change in Individual Item Scores on HAM-A
Intellectual- Week 8- Change from baseline
-0.9 units on a scale
Standard Deviation 1.1
-0.8 units on a scale
Standard Deviation 1.1
-0.9 units on a scale
Standard Deviation 1.1
Change in Individual Item Scores on HAM-A
Depressed Mood- Week 4- Change in baseline
-0.4 units on a scale
Standard Deviation 0.9
-0.3 units on a scale
Standard Deviation 0.9
-0.3 units on a scale
Standard Deviation 0.8
Change in Individual Item Scores on HAM-A
Depressed Mood- Week 6- Change from baseline
-0.3 units on a scale
Standard Deviation 0.9
-0.3 units on a scale
Standard Deviation 0.9
-0.3 units on a scale
Standard Deviation 0.8
Change in Individual Item Scores on HAM-A
Depressed Mood- Week 8- Change from baseline
-0.4 units on a scale
Standard Deviation 0.9
-0.4 units on a scale
Standard Deviation 0.9
-0.3 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Somatic Complaints-Muscular-Baseline
2.0 units on a scale
Standard Deviation 0.8
1.9 units on a scale
Standard Deviation 0.8
1.8 units on a scale
Standard Deviation 0.8
Change in Individual Item Scores on HAM-A
Somatic Complaints-Muscular-Wk 2-Chg from baseline
-0.5 units on a scale
Standard Deviation 1.0
-0.3 units on a scale
Standard Deviation 0.8
-0.5 units on a scale
Standard Deviation 0.8
Change in Individual Item Scores on HAM-A
Somatic Complaints-Muscular-Wk 4-Chg from baseline
-0.7 units on a scale
Standard Deviation 0.9
-0.5 units on a scale
Standard Deviation 1.0
-0.6 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Somatic Complaints-Muscular-Wk 6-Chg from baseline
-0.8 units on a scale
Standard Deviation 1.1
-0.7 units on a scale
Standard Deviation 1.1
-0.6 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Somatic Complaints-Muscular-Wk 8-Chg from baseline
-0.9 units on a scale
Standard Deviation 1.1
-0.7 units on a scale
Standard Deviation 1.1
-0.7 units on a scale
Standard Deviation 1.1
Change in Individual Item Scores on HAM-A
Somatic Complaints-Sensory-Wk 2-Chg from baseline
-0.3 units on a scale
Standard Deviation 0.9
-0.2 units on a scale
Standard Deviation 0.8
-0.5 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Somatic Complaints-Sensory-Wk 4-Chg from baseline
-0.4 units on a scale
Standard Deviation 0.9
-0.3 units on a scale
Standard Deviation 1.0
1.0 units on a scale
Standard Deviation 0.9
Change in Individual Item Scores on HAM-A
Somatic Complaints-Sensory-Wk 6-Chg from baseline
-0.4 units on a scale
Standard Deviation 0.9
-0.4 units on a scale
Standard Deviation 0.9
-0.5 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Somatic Complaints-Sensory-Wk 8-Chg from baseline
-0.5 units on a scale
Standard Deviation 1.0
-0.4 units on a scale
Standard Deviation 1.0
-0.5 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Cardiovascular symptoms-baseline
1.1 units on a scale
Standard Deviation 1.0
1.2 units on a scale
Standard Deviation 1.0
1.3 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Cardiovascular symptoms-Wk 2-Chg. from baseline
-0.4 units on a scale
Standard Deviation 1.0
-0.4 units on a scale
Standard Deviation 0.9
-0.5 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Cardiovascular symptoms-Wk 4-Chg. from baseline
-0.5 units on a scale
Standard Deviation 1.0
-0.7 units on a scale
Standard Deviation 1.0
-0.6 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Cardiovascular symptoms-Wk 6-Chg. from baseline
-0.6 units on a scale
Standard Deviation 1.0
-0.6 units on a scale
Standard Deviation 1.0
-0.6 units on a scale
Standard Deviation 1.0
Change in Individual Item Scores on HAM-A
Cardiovascular symptoms-Wk 8-Chg. from baseline
-0.7 units on a scale
Standard Deviation 1.0
-0.8 units on a scale
Standard Deviation 1.0
-0.7 units on a scale
Standard Deviation 1.1

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, based on last observation carried forward (LOCF)

Population: ITT Population: The ITT population will include all randomized subjects who received at least one dose of study medication during the double-blind period.

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.

Outcome measures

Outcome measures
Measure
Placebo Arm
n=149 Participants
Placebo
Eszopiclone Low Dose Arm
n=146 Participants
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 Participants
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Change From Baseline in Clinician Global Impression of Severity (CGI-S)
Baseline
4.4 units on a scale
Standard Deviation 0.5
4.3 units on a scale
Standard Deviation 0.5
4.4 units on a scale
Standard Deviation 0.6
Change From Baseline in Clinician Global Impression of Severity (CGI-S)
Week 4- Change from baseline
-0.9 units on a scale
Standard Deviation 0.9
-0.8 units on a scale
Standard Deviation 0.8
-1.0 units on a scale
Standard Deviation 1.1
Change From Baseline in Clinician Global Impression of Severity (CGI-S)
Week 2 - Change from baseline
-0.6 units on a scale
Standard Deviation 0.9
-0.4 units on a scale
Standard Deviation 0.6
-0.7 units on a scale
Standard Deviation 0.9
Change From Baseline in Clinician Global Impression of Severity (CGI-S)
Week 6- Change from baseline
-1.1 units on a scale
Standard Deviation 1.0
-1.0 units on a scale
Standard Deviation 1.0
-1.2 units on a scale
Standard Deviation 1.2
Change From Baseline in Clinician Global Impression of Severity (CGI-S)
Week 8- Change from baseline
-1.3 units on a scale
Standard Deviation 1.1
-1.2 units on a scale
Standard Deviation 1.1
-1.3 units on a scale
Standard Deviation 1.3

SECONDARY outcome

Timeframe: Weeks 2, 4, 6, 8, and 9, based on last observation carried forward (LOCF)

Population: ITT Population: The ITT population will include all randomized subjects who received at least one dose of study medication during the double-blind period.

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.

Outcome measures

Outcome measures
Measure
Placebo Arm
n=149 Participants
Placebo
Eszopiclone Low Dose Arm
n=146 Participants
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 Participants
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Clinical Global Impression- Improvement (CGI-I)
Week 2
3.2 units on a scale
Standard Deviation 1.0
3.2 units on a scale
Standard Deviation 0.9
3.1 units on a scale
Standard Deviation 1.0
Clinical Global Impression- Improvement (CGI-I)
Week 4
2.9 units on a scale
Standard Deviation 1.0
2.9 units on a scale
Standard Deviation 0.9
2.7 units on a scale
Standard Deviation 1.2
Clinical Global Impression- Improvement (CGI-I)
Week 6
2.7 units on a scale
Standard Deviation 1.0
2.6 units on a scale
Standard Deviation 1.1
2.7 units on a scale
Standard Deviation 1.2
Clinical Global Impression- Improvement (CGI-I)
Week 8
2.6 units on a scale
Standard Deviation 1.1
2.6 units on a scale
Standard Deviation 1.1
2.6 units on a scale
Standard Deviation 1.2
Clinical Global Impression- Improvement (CGI-I)
Week 9
2.4 units on a scale
Standard Deviation 1.1
2.5 units on a scale
Standard Deviation 1.1
2.4 units on a scale
Standard Deviation 1.2

SECONDARY outcome

Timeframe: Week 2, 4, 6, 8

Population: ITT Population: The ITT population will include all randomized subjects who received at least one dose of study medication during the double-blind period.

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.

Outcome measures

Outcome measures
Measure
Placebo Arm
n=149 Participants
Placebo
Eszopiclone Low Dose Arm
n=146 Participants
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 Participants
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Hamilton Anxiety Scale (HAM-A) 50% Anxiolytic Response
Week 2
21 participants
16 participants
27 participants
Hamilton Anxiety Scale (HAM-A) 50% Anxiolytic Response
Week 8
63 participants
57 participants
66 participants
Hamilton Anxiety Scale (HAM-A) 50% Anxiolytic Response
Week 4
39 participants
41 participants
49 participants
Hamilton Anxiety Scale (HAM-A) 50% Anxiolytic Response
Week 6
51 participants
52 participants
53 participants

SECONDARY outcome

Timeframe: Week 2, 4, 6, 8 based on last observation carried forward (LOCF)

Population: ITT Population: The ITT population will include all randomized subjects who received at least one dose of study medication during the double-blind period.

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.

Outcome measures

Outcome measures
Measure
Placebo Arm
n=149 Participants
Placebo
Eszopiclone Low Dose Arm
n=146 Participants
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 Participants
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Hamilton Anxiety Scale (HAM-A) Remission
Week 2
7 participants
2 participants
9 participants
Hamilton Anxiety Scale (HAM-A) Remission
Week 4
11 participants
10 participants
24 participants
Hamilton Anxiety Scale (HAM-A) Remission
Week 6
22 participants
19 participants
23 participants
Hamilton Anxiety Scale (HAM-A) Remission
Week 8
31 participants
29 participants
34 participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, based on last observation carried forward (LOCF)

Population: ITT Population: The ITT population will include all randomized subjects who received at least one dose of study medication during the double-blind period.

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.

Outcome measures

Outcome measures
Measure
Placebo Arm
n=149 Participants
Placebo
Eszopiclone Low Dose Arm
n=146 Participants
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 Participants
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Change From Baseline on Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form
Baseline
52.4 units on a scale
Standard Deviation 14.9
52.2 units on a scale
Standard Deviation 13.5
52.0 units on a scale
Standard Deviation 14.8
Change From Baseline on Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form
Week 2- Change from baseline
3.1 units on a scale
Standard Deviation 10.6
2.1 units on a scale
Standard Deviation 13.2
1.5 units on a scale
Standard Deviation 12.1
Change From Baseline on Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form
Week 4- Change from baseline
4.7 units on a scale
Standard Deviation 12.4
5.4 units on a scale
Standard Deviation 12.7
4.6 units on a scale
Standard Deviation 12.8
Change From Baseline on Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form
Week 6- Change from baseline
5.8 units on a scale
Standard Deviation 13.7
6.7 units on a scale
Standard Deviation 13.4
5.0 units on a scale
Standard Deviation 13.6
Change From Baseline on Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form
Week 8- Change from baseline
7.0 units on a scale
Standard Deviation 14.8
6.8 units on a scale
Standard Deviation 13.2
5.8 units on a scale
Standard Deviation 14.6

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, based on lst observation carried forward (LOCF)

Population: ITT Population: The ITT population will include all randomized subjects who received at least one dose of study medication during the double-blind period.

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.

Outcome measures

Outcome measures
Measure
Placebo Arm
n=149 Participants
Placebo
Eszopiclone Low Dose Arm
n=146 Participants
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 Participants
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Change From Baseline Insomnia Severity Index (ISI) Total Score
Baseline
14.6 units on a scale
Standard Deviation 5.3
14.3 units on a scale
Standard Deviation 5.3
14.1 units on a scale
Standard Deviation 6.0
Change From Baseline Insomnia Severity Index (ISI) Total Score
Week 2- Change from baseline
-2.4 units on a scale
Standard Deviation 4.4
-1.5 units on a scale
Standard Deviation 5.0
-2.7 units on a scale
Standard Deviation 5.3
Change From Baseline Insomnia Severity Index (ISI) Total Score
Week 4- Change from baseline
-3.6 units on a scale
Standard Deviation 4.8
-3.1 units on a scale
Standard Deviation 5.4
-3.4 units on a scale
Standard Deviation 5.3
Change From Baseline Insomnia Severity Index (ISI) Total Score
Week 6- Change from baseline
-4.0 units on a scale
Standard Deviation 5.6
-3.6 units on a scale
Standard Deviation 5.5
-3.6 units on a scale
Standard Deviation 5.6
Change From Baseline Insomnia Severity Index (ISI) Total Score
Week 8- Change from baseline
-4.3 units on a scale
Standard Deviation 5.6
-3.5 units on a scale
Standard Deviation 6.2
-4.1 units on a scale
Standard Deviation 5.8

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, based on last observation carried forward (LOCF)

Population: ITT Population: The ITT population will include all randomized subjects who received at least one dose of study medication during the double-blind period.

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.

Outcome measures

Outcome measures
Measure
Placebo Arm
n=149 Participants
Placebo
Eszopiclone Low Dose Arm
n=146 Participants
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 Participants
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Change From Baseline Sheehan Disability Scale (SDS)
Week 8- Change from baseline
-5.1 units on a scale
Standard Deviation 6.6
-4.1 units on a scale
Standard Deviation 6.5
-4.4 units on a scale
Standard Deviation 6.2
Change From Baseline Sheehan Disability Scale (SDS)
Week 4- Change from baseline
-3.6 units on a scale
Standard Deviation 6.1
-2.5 units on a scale
Standard Deviation 6.3
-3.5 units on a scale
Standard Deviation 6.1
Change From Baseline Sheehan Disability Scale (SDS)
Week 6- Change from baseline
-4.2 units on a scale
Standard Deviation 6.5
-3.4 units on a scale
Standard Deviation 6.3
-4.1 units on a scale
Standard Deviation 6.2
Change From Baseline Sheehan Disability Scale (SDS)
Baseline
15.3 units on a scale
Standard Deviation 6.7
14.0 units on a scale
Standard Deviation 6.4
14.8 units on a scale
Standard Deviation 6.4
Change From Baseline Sheehan Disability Scale (SDS)
Week 2- Change from baseline
-2.5 units on a scale
Standard Deviation 5.5
-0.9 units on a scale
Standard Deviation 6.3
-2.7 units on a scale
Standard Deviation 5.3

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, based on last observation carried forward (LOCF)

Population: ITT Population: The ITT population will include all randomized subjects who received at least one dose of study medication during the double-blind period.

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.

Outcome measures

Outcome measures
Measure
Placebo Arm
n=149 Participants
Placebo
Eszopiclone Low Dose Arm
n=146 Participants
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 Participants
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Change From Baseline Epworth Sleepiness Scale (ESS)
Baseline
7.4 units on a scale
Standard Deviation 4.5
8.4 units on a scale
Standard Deviation 4.5
8.5 units on a scale
Standard Deviation 4.8
Change From Baseline Epworth Sleepiness Scale (ESS)
Week 2- Change from baseline
-0.1 units on a scale
Standard Deviation 4.0
-0.5 units on a scale
Standard Deviation 3.8
-0.4 units on a scale
Standard Deviation 3.6
Change From Baseline Epworth Sleepiness Scale (ESS)
Week 4- Change from baseline
-0.2 units on a scale
Standard Deviation 4.6
-1.0 units on a scale
Standard Deviation 4.1
-0.7 units on a scale
Standard Deviation 4.5
Change From Baseline Epworth Sleepiness Scale (ESS)
Week 6- Change from baseline
-0.6 units on a scale
Standard Deviation 4.0
-1.3 units on a scale
Standard Deviation 4.0
-0.9 units on a scale
Standard Deviation 4.5
Change From Baseline Epworth Sleepiness Scale (ESS)
Week 8- Change from baseline
-0.8 units on a scale
Standard Deviation 4.0
-1.4 units on a scale
Standard Deviation 4.2
-1.3 units on a scale
Standard Deviation 4.5

Adverse Events

Placebo Arm

Serious events: 0 serious events
Other events: 104 other events
Deaths: 0 deaths

Eszopiclone Low Dose Arm

Serious events: 3 serious events
Other events: 111 other events
Deaths: 0 deaths

Eszopiclone High Dose Arm

Serious events: 0 serious events
Other events: 116 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo Arm
n=149 participants at risk
Placebo
Eszopiclone Low Dose Arm
n=146 participants at risk
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 participants at risk
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Infections and infestations
Amniotic Cavity Infection
0.00%
0/149 • 10 weeks
0.68%
1/146 • Number of events 1 • 10 weeks
0.00%
0/145 • 10 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon Cancer
0.00%
0/149 • 10 weeks
0.68%
1/146 • Number of events 1 • 10 weeks
0.00%
0/145 • 10 weeks
Injury, poisoning and procedural complications
Traumatic Brain Injury
0.00%
0/149 • 10 weeks
0.68%
1/146 • Number of events 1 • 10 weeks
0.00%
0/145 • 10 weeks
Psychiatric disorders
Self Injurious Behavior
0.00%
0/149 • 10 weeks
0.68%
1/146 • Number of events 1 • 10 weeks
0.00%
0/145 • 10 weeks
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous
0.00%
0/149 • 10 weeks
0.68%
1/146 • Number of events 1 • 10 weeks
0.00%
0/145 • 10 weeks

Other adverse events

Other adverse events
Measure
Placebo Arm
n=149 participants at risk
Placebo
Eszopiclone Low Dose Arm
n=146 participants at risk
SEP-225441 (eszopiclone) total daily dose of 0.9 mg
Eszopiclone High Dose Arm
n=145 participants at risk
SEP-225441 (eszopiclone) total daily dose of 1.5 mg
Gastrointestinal disorders
Nausea
9.4%
14/149 • Number of events 19 • 10 weeks
4.8%
7/146 • Number of events 8 • 10 weeks
12.4%
18/145 • Number of events 21 • 10 weeks
Gastrointestinal disorders
Diarrhoea
7.4%
11/149 • Number of events 11 • 10 weeks
3.4%
5/146 • Number of events 5 • 10 weeks
9.0%
13/145 • Number of events 16 • 10 weeks
Gastrointestinal disorders
Dry Mouth
4.0%
6/149 • Number of events 7 • 10 weeks
5.5%
8/146 • Number of events 8 • 10 weeks
8.3%
12/145 • Number of events 12 • 10 weeks
Gastrointestinal disorders
Abdominal Pain Upper
6.7%
10/149 • Number of events 11 • 10 weeks
6.2%
9/146 • Number of events 12 • 10 weeks
9.7%
14/145 • Number of events 20 • 10 weeks
General disorders
Fatigue
8.1%
12/149 • Number of events 14 • 10 weeks
8.2%
12/146 • Number of events 12 • 10 weeks
2.8%
4/145 • Number of events 4 • 10 weeks
Infections and infestations
Upper Respiratory Tract Infection
4.0%
6/149 • Number of events 7 • 10 weeks
8.2%
12/146 • Number of events 12 • 10 weeks
2.8%
4/145 • Number of events 4 • 10 weeks
Infections and infestations
Nasaopharyngitis
3.4%
5/149 • Number of events 6 • 10 weeks
4.1%
6/146 • Number of events 6 • 10 weeks
5.5%
8/145 • Number of events 9 • 10 weeks
Musculoskeletal and connective tissue disorders
Back Pain
2.0%
3/149 • Number of events 3 • 10 weeks
6.8%
10/146 • Number of events 11 • 10 weeks
2.8%
4/145 • Number of events 5 • 10 weeks
Nervous system disorders
Headache
18.1%
27/149 • Number of events 47 • 10 weeks
17.8%
26/146 • Number of events 44 • 10 weeks
16.6%
24/145 • Number of events 41 • 10 weeks
Nervous system disorders
Dysgeusia
2.0%
3/149 • Number of events 3 • 10 weeks
6.8%
10/146 • Number of events 16 • 10 weeks
24.1%
35/145 • Number of events 37 • 10 weeks
Nervous system disorders
Dizziness
4.0%
6/149 • Number of events 7 • 10 weeks
7.5%
11/146 • Number of events 15 • 10 weeks
11.0%
16/145 • Number of events 20 • 10 weeks
Nervous system disorders
Somnolence
4.7%
7/149 • Number of events 7 • 10 weeks
5.5%
8/146 • Number of events 8 • 10 weeks
6.9%
10/145 • Number of events 11 • 10 weeks
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal Pain
2.0%
3/149 • Number of events 3 • 10 weeks
5.5%
8/146 • Number of events 8 • 10 weeks
0.69%
1/145 • Number of events 1 • 10 weeks

Additional Information

Eszopiclone Medical Director

Sunovion

Phone: 866-503-7813

Results disclosure agreements

  • Principal investigator is a sponsor employee In the event the Study is part of a multi-center study, the first publication of the results of the Study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, Institution and Investigator shall be free to publish
  • Publication restrictions are in place

Restriction type: OTHER