A Long-Term Safety and Efficacy Study of Eszopiclone in Elderly With Primary Chronic Insomnia

A Long-Term Safety and Efficacy Study of Eszopiclone in Elderly Subjects With Primary Chronic Insomnia

To evaluate the long-term safety and efficacy of eszopiclone administered for 12 weeks in elderly subjects with primary chronic insomnia.Administration of eszopiclone 2 mg daily at bedtime for 12 weeks in elderly subjects with a diagnosis of primary chronic insomnia will be safe and well tolerated, improve subjective sleep measures, improve measures of Quality of Life and next day insomnia symptoms, and have no significant withdrawal central nervous system adverse events or rebound insomnia.

A double-blind, randomized, placebo controlled, parallel group study of eszopiclone in elderly subjects with primary chronic insomnia. The study will involve up to 9 visits and subject participation will be approximately 18 weeks. This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.

Week -2 to day 0 single blind one tablet placebo in the evening. Double blind period: Day 1 to Week 12 double blind one tablet placebo in the evening. Follow up period: two weeks (Weeks 13-14) single blind one tablet placebo in evening, and two weeks (Weeks 15-16) no drug washout.

Week -2 to day 0 single blind one tablet placebo in evening. Double Blind period: Day 1 to Week 12 double blind one tablet 2 mg of eszopiclone in evening. Follow up period consists of two weeks (Weeks 13-14) single blind one tablet placebo in evening, and two weeks (Weeks 15-16) no drug washout.

Mean Change From Baseline in Subject-Reported Total Sleep Time (TST) Averaged Over the 12 Week Double Blind Study Period.

The difference between the total sleep time at baseline and the average total sleep time over the double blind period(average of post-dose values from weeks 3,6,9,12) reported by the participant. The change is calculated as the average over the double blind period minus the baseline value.

The difference between the total sleep time at baseline and at different time points in the double-blind period (weeks 3,6,9,12), the single-blind follow-up (week 14) and the non-drug treatment follow-up (week 16). The change is calculated as the time point value minus the baseline value.

The mean total minutes asleep each night at different time points: baseline(week 0), double-blind phase(weeks 3,6,9,12), the single-blind follow-up(week 14),the non-drug treatment follow-up(week 16), and the double-blind average(average of weeks 3,6,9,12 values).

Mean Change From Baseline in Subject-reported Sleep Latency (SL) Averaged Over the 12 Week Double Blind Period.

Sleep latency answers how long it takes to fall asleep. The difference between the sleep latency at baseline and the average sleep latency over the double blind period(average of post-dose values from weeks 3,6,9,12) reported by the participant. The change is calculated as the average over the double blind period minus the baseline value.

Sleep latency answers the question: How long did it take you to fall asleep last night? The change is calculated as value during double-blind phase(weeks 3,6,9,12), or the single-blind follow-up(week 14), or the non-drug treatment follow-up(week 16) minus the baseline value.

Sleep latency answers the question: How long did it take you to fall asleep last night? Mean values are reported at baseline(week 0), double-blind phase(weeks 3,6,9,12), single-blind follow-up(week 14), non-drug treatment follow-up(week 16), and the average for the entire double-blind phase(average of weeks 3,6,9,12 values).

Mean Change From Baseline in Subject-reported Wake Time After Sleep Onset (WASO) Averaged Over the 12 Week Double-blind Study Period.

Wake time after sleep onset (WASO) is the time spent awake from sleep onset to final awakening. The difference between WASO at baseline and the average WASO over the double blind period(average of post-dose values from weeks 3,6,9,12). The change is calculated as the average over the double blind period minus the baseline value.

Mean Change From Baseline in Subject-reported Wake Time After Sleep Onset (WASO) at Various Study Time Points.

Wake time after sleep onset is the time spent awake from sleep onset to final awakening. The change is calculated as value during double-blind phase(weeks 3,6,9,12), or the single-blind follow-up(week 14), or the non-drug treatment follow-up(week 16) minus the baseline value.

Wake time after sleep onset is the time spent awake from sleep onset to final awakening. Mean values are reported at baseline(week 0), double-blind phase(weeks 3,6,9,12), single-blind follow-up(week 14), non-drug treatment follow-up(week 16), and the average for the entire double-blind phase(average of weeks 3,6,9,12 values).

Mean Change From Baseline in Subject-reported Number of Awakenings Averaged Over the 12 Week Double Blind Study Period.

The number of awakenings is the number of times a subject wakes up between the initial onset of sleep and the final awakening. The change is calculated as the average over the double blind period (average of post-dose values from weeks 3,6,9,12) minus the baseline value.

The number of awakenings refers to the number of times a subject wakes up between the initial onset of sleep and the final awakening. The change is calculated as value during double-blind phase(weeks 3,6,9,12), or the single-blind follow-up(week 14), or the non-drug treatment follow-up(week 16) minus the baseline value.

Number of awakenings is number of times a subject wakes up between initial onset of sleep and final awakening. Mean values are reported at baseline(week 0), double-blind phase(weeks 3,6,9,12), single-blind follow-up(week 14), non-drug treatment follow-up(week 16), and the average for the double-blind phase(average of weeks 3,6,9,12 values).

Mean Change From Baseline in Subject-reported Quality of Sleep Averaged Over the 12 Week Double Blind Study Period

Quality of sleep was rated by participants on a scale of 0-10, with higher scores representing better quality sleep. The change is calculated as the average over the double blind period (average of post-dose values from weeks 3,6,9,12) minus the baseline value.

Sleep quality was rated by subjects on a scale from 0-10, with higher scores representing better quality sleep. The change is calculated as value during double-blind phase(weeks 3,6,9,12), or the single-blind follow-up(week 14), or the non-drug treatment follow-up(week 16) minus the baseline value.

Quality of sleep was rated by participants on a scale of 0-10, with higher scores representing better quality sleep. Mean values are reported at baseline(week 0), double-blind phase(weeks 3,6,9,12), single-blind follow-up(week 14), non-drug treatment follow-up(week 16), and the average for the double-blind phase(average of weeks 3,6,9,12 values).

Mean Change From Baseline in Subject-Reported Depth of Sleep for the Average Reported During the Double-blind Period.

Depth of sleep was reported by study participants using a scale from 0-10, with higher scores representing better sleep. The change is calculated as the average over the double blind period (average of post-dose values from weeks 3,6,9,12) minus the baseline value.

Depth of sleep was reported by study participants using a scale from 0-10, with higher scores representing better sleep. The change is calculated as value during double-blind phase(weeks 3,6,9,12), or the single-blind follow-up(week 14), or the non-drug treatment follow-up(week 16) minus the baseline value.

Depth of sleep was reported by study participants using a scale from 0-10, with higher scores representing better sleep. Mean values reported: baseline(week 0), double-blind phase(weeks 3,6,9,12), single-blind follow-up(week 14), non-drug treatment follow-up(week 16), and the average for the double-blind phase(average of weeks 3,6,9,12 values).

Mean Change in Subject-reported Daytime Alertness Averaged Over the 12 Week Double Blind Study Period

Daytime alertness was rated by study participants on a scale of 0-10, with higher scores representing better alertness. The change is calculated as the average over the double blind period (average of post-dose values from weeks 3,6,9,12) minus the baseline value.

Daytime alertness was rated by study participants on a scale of 0-10, with higher scores representing better alertness. The change is calculated as value during double-blind phase(weeks 3,6,9,12), or the single-blind follow-up(week 14), or the non-drug treatment follow-up(week 16) minus the baseline value.

Daytime alertness was rated by study participants on a scale of 0-10, with higher scores representing better alertness. Mean values reported: baseline(week 0), double-blind phase(weeks 3,6,9,12), single-blind follow-up(week 14), non-drug treatment follow-up(week 16), and the average for the double-blind phase(average of weeks 3,6,9,12 values).

Mean Change From Baseline in Subject-Reported Ability to Function Averaged Over the 12 Week Double Blind Period

Ability to function was rated by study participants on a scale of 0-10, with higher scores representing better ability to function. The change is calculated as the average over the double blind period (average of post-dose values from weeks 3,6,9,12) minus the baseline value.

Ability to function was rated by study participants on a scale of 0-10, with higher scores representing better ability to function. The change is calculated as value during double-blind phase(weeks 3,6,9,12), or the single-blind follow-up(week 14), or the non-drug treatment follow-up(week 16) minus the baseline value.

Ability to function was rated by study participants on a scale of 0-10, with higher scores representing better ability to function. Mean values reported: baseline(week 0), double-blind phase(weeks 3,6,9,12), single-blind follow-up(week 14), non-drug treatment follow-up(week 16) & average for double-blind phase(average of weeks 3,6,9,12 values).

Mean Change From Baseline in Subject-reported Ability to Concentrate Averaged Over the 12 Week Double Blind Study Period.

Ability to concentrate was rated by study participants on a scale of 0-10, with higher scores representing better concentration. The change is calculated as the average over the double blind period (average of post-dose values from weeks 3,6,9,12) minus the baseline value.

Ability to concentrate was rated by study participants on a scale of 0-10, with higher scores representing better concentration. The change is calculated as value during double-blind phase(weeks 3,6,9,12), or the single-blind follow-up(week 14), or the non-drug treatment follow-up(week 16) minus the baseline value.

Ability to concentrate was rated by study participants on a scale of 0-10, with higher scores representing better concentration. Mean values reported: baseline(week 0), double-blind phase(weeks 3,6,9,12), single-blind follow-up(week 14), non-drug treatment follow-up(week 16) & average for the double-blind phase(average of weeks 3,6,9,12 values).

Mean Change From Baseline in Subject-reported Physical Well-Being Averaged Over the 12 Week Double Blind Study Period

Physical well-being was rated by study participants on a scale of 0-10, with higher scores representing better well-being. The change is calculated as the average over the double blind period (average of post-dose values from weeks 3,6,9,12) minus the baseline value.

Physical well-being was rated by study participants on a scale of 0-10, with higher scores representing better well-being. The change is calculated as value during double-blind phase(weeks 3,6,9,12), or the single-blind follow-up(week 14), or the non-drug treatment follow-up(week 16) minus the baseline value.

Physical well-being was rated by study participants on a scale of 0-10, with higher scores representing better well-being. Mean values reported: baseline(week 0), double-blind phase(weeks 3,6,9,12), single-blind follow-up(week 14), non-drug treatment follow-up(week 16), & average for double-blind phase(average of weeks 3,6,9,12 values).

Mean Change From Baseline in Subject-Reported Counts of Number of Naps Per Week Averaged Over the 12 Week Double Blind Study Period

Change from baseline in the number of naps per week for subjects who napped during the baseline period. The change is calculated as the average over the double blind period (average of post-dose values from weeks 3,6,9,12) minus the baseline value.

Mean Change From Baseline In Subject-Reported Counts of Number of Naps Per Week at Various Study Time Points

Change from baseline in the number of naps per week for subjects who napped during the baseline period. The change is calculated as value during double-blind phase(weeks 3,6,9,12), or the single-blind follow-up(week 14), or the non-drug treatment follow-up(week 16) minus the baseline value.

The mean number of naps per week for subjects who napped during the baseline period. Mean values are reported at baseline(week 0), double-blind phase(weeks 3,6,9,12), single-blind follow-up(week 14), non-drug treatment follow-up(week 16), and the average for the double-blind phase(average of weeks 3,6,9,12 values).

Mean Change in Subject-Reported Total Nap Time Per Week Averaged Over the 12 Week Double Blind Study Period

Change from baseline in the total time (minutes) spent napping per week for subjects who napped during the baseline period. The change is calculated as the average over the double blind period (average of post-dose values from weeks 3,6,9,12) minus the baseline value.

Change from baseline in the total time (minutes) spent napping per week for subjects who napped during the baseline period. The change is calculated as value during double-blind phase(weeks 3,6,9,12), or the single-blind follow-up(week 14), or the non-drug treatment follow-up(week 16) minus the baseline value.

The total time (minutes) spent napping per week for subjects who napped during the baseline period. Mean values are reported at baseline(week 0), double-blind phase(weeks 3,6,9,12), single-blind follow-up(week 14), non-drug treatment follow-up(week 16), and the average for the double-blind phase(average of weeks 3,6,9,12 values).

Mean Change From Baseline in Subject-Reported Total Nap Time Per Week as a Percent of Total Asleep Time Averaged Over the 12 Week Double Blind Study Period

Change from baseline in the total time spent napping per week stated as a percentage of the total time asleep for subjects who napped during the baseline period. The change is calculated as the average over the double blind period (average of post-dose values from weeks 3,6,9,12) minus the baseline value.

Mean Change From Baseline in Subject-Reported Total Nap Time Stated as a Percentage of the Total Asleep Time at Various Study Time Points

Change from baseline in the total time spent napping per week stated as a percentage of the total time asleep for subjects who napped during the baseline period. The change is calculated as value during double-blind phase(weeks 3,6,9,12), or the single-blind follow-up(week 14), or the non-drug treatment follow-up(week 16) minus the baseline value.

Mean Subject-Reported Total Nap Time Per Week Stated as a Percentage of the Total Asleep Time at Various Study Time Points

Total time spent napping per week stated as a percentage of total time asleep for subjects who napped during baseline period. Mean values reported: baseline(week 0), double-blind phase(weeks 3,6,9,12), single-blind follow-up(week14), non-drug treatment follow-up(week 16), & average for double-blind phase(average of weeks 3,6,9,12 values).

Mean Change From Baseline in Total Sleep Time Measured by Actigraphy Averaged Over the 12 Week Double Blind Study Period

Participants who wore an actigraph wrist monitor, which monitors rest and activity cycles are included; the resultant data had total sleep time calculated by a Central Reader. The change is calculated as the average over the double blind period (average of post-dose values from weeks 1,4,7,12) minus the baseline value.

Change from baseline in total sleep time for the subset population who wore an actigraph wrist monitor. The actigraph monitors rest and activity cycles; the resultant data had sleep parameters calculated by a Central Reader. The change is calculated as time point value minus the baseline value.

Total sleep time for subset who wore actigraph wrist monitor which monitors rest and activity cycles, sleep parameters calculated by Central Reader. Mean values reported:baseline(week0), double-blind(weeks1,4,7,12), single-blind follow-up(week13), non-drug follow-up(week15) & average for double-blind(average of weeks1,4,7,12 values).

Mean Change From Baseline in Sleep Latency Measured Using Actigraphy Averaged Over the 12 Week Double Blind Study Period

Sleep latency is the time it takes to fall asleep. Participants who wore an actigraph wrist monitor to record rest and activity cycles are included; a Central Reader calculated sleep parameters. The change is calculated as the average over the double blind period (average of post-dose values from weeks 1,4,7,12) minus the baseline value.

Sleep latency is a measurement of the time it takes to fall asleep. Participants who wore an actigraph wrist monitor to record rest and activity cycles are included; a Central Reader calculated sleep parameters. The change is calculated as time point value minus the baseline value.

Sleep latency:measurement of time to fall asleep. Values are for subset who wore an actigraph wrist monitor which monitors rest and activity cycles; sleep parameters calculated by Central Reader.

Mean Change From Baseline in Wake Time After Sleep Onset (WASO) Measured by Actigraphy Averaged Over the 12 Week Double Blind Study Period

Wake time after sleep onset is the time spent awake from sleep onset to final awakening. Change is calculated as average over double blind period (average of post-dose values from weeks 1,4,7,12) minus the baseline value.

Mean Change From Baseline in Wake Time After Sleep Onset Measured Using Actigraphy at Various Study Time Points

Wake time after sleep onset is the time spent awake from sleep onset to final awakening. Participants who wore an actigraph wrist monitor to record rest and activity cycles are included; a Central Reader calculated sleep parameters. The change is calculated as time point value minus the baseline value.

Wake time after sleep onset is time spent awake from sleep onset to final awakening. Mean values reported: baseline(week 0), double-blind phase(weeks 1,4,7,12), single-blind follow-up(week 13), non-drug treatment follow-up(week 15) & average for double-blind phase(average of weeks 1,4,7,12 values).

Mean Change From Baseline in Number of Awakenings Using Actigraphy Averaged Over the 12 Week Double Blind Study Period

Number of awakenings refers to the number of times a subject awakens between first sleep onset to final awakening. Change is calculated as average over double blind period (average of post-dose values from weeks 1,4,7,12) minus the baseline value.

Mean Change From Baseline in the Number of Awakenings Measured Using Actigraphy at Various Study Time Points.

Number of awakenings refers to the number of times a subject awakens between first sleep onset to final awakening. Participants who wore an actigraph wrist monitor to record rest and activity cycles are included; a Central Reader calculated sleep parameters. The change is calculated as time point value minus the baseline value.

Number of awakenings refers to the number of times a subject awakens between first sleep onset to final awakening. Mean values are reported at baseline(week 0), double-blind phase(weeks 1,4,7,12), single-blind follow-up(week 13), non-drug treatment follow-up(week 15), and the average for the double-blind phase(average of weeks 1,4,7,12 values).

Mean Change From Baseline in Number of Naps Per Week Measured Using Actigraphy Averaged Over the 12 Week Double Blind Study Period

Change from baseline in the number of naps per week for subjects who napped during the baseline period. Change is calculated as the average over the double blind period (average of post-dose values from weeks 1,4,7,12) minus the baseline value.

Mean Change From Baseline in the Number of Naps Per Week Measured Using Actigraphy at Various Study Time Points

Change from baseline in the number of naps per week for subjects who napped during the baseline period. Participants who wore an actigraph wrist monitor to record rest and activity cycles are included; a Central Reader calculated sleep parameters. The change is calculated as time point value minus the baseline value.

The number of naps per week for subjects who napped during the baseline period. Mean values are reported at baseline(week 0), double-blind phase(weeks 1,4,7,12), single-blind follow-up(week 13), non-drug treatment follow-up(week 15), and the average for the double-blind phase(average of weeks 1,4,7,12 values).

Mean Change From Baseline Total Nap Time Per Week Measured by Actigraphy Averaged Over the 12 Week Double Blind Study Period

Change from baseline in the total nap time per week for subjects who napped during the baseline period. Change is calculated as the average over the double blind period (average of post-dose values from weeks 1,4,7,12) minus the baseline value.

Mean Change From Baseline in Total Nap Time Per Week Measured by Actigraphy at Various Study Time Points

Change from baseline in the total nap time per week for subjects who napped during the baseline period. Participants who wore an actigraph wrist monitor to record rest and activity cycles are included; a Central Reader calculated sleep parameters. The change is calculated as time point value minus the baseline value.

The total nap time per week for subjects who napped during the baseline period. Mean values are reported at baseline(week 0), double-blind phase(weeks 1,4,7,12), single-blind follow-up(week 13), non-drug treatment follow-up(week 15), and the average for the double-blind phase(average of weeks 1,4,7,12 values).

Mean Change From Baseline in Total Nap Time Per Week as a Percentage of Total Asleep Time Measured by Actigraphy and Averaged Over the 12 Week Double Blind Study Period.

Change from baseline in the total time spent napping per week as a percent of the total time asleep for subjects who napped during the baseline period. Change is calculated as the average over the double blind period (average of post-dose values from weeks 1,4,7,12) minus the baseline value.

Mean Change From Baseline in Total Nap Time Per Week as a Percentage of Total Asleep Time as Measured by Actigraphy at Various Study Time Points

Change from baseline in total time spent napping per week as a percent of total time asleep for subjects who napped during the baseline period. Change is calculated as time point value minus the baseline value.

Mean Total Nap Time Per Week as a Percentage of Total Asleep Time Measured Using Actigraphy at Various Study Time Points

The total time spent napping per week as a percent of the total time asleep for subjects who napped during the baseline period. Mean values reported: baseline(week 0), double-blind phase(weeks 1,4,7,12), single-blind follow-up(week 13), non-drug treatment follow-up(week 15) & average for double-blind phase(average of weeks 1,4,7,12 values).

Mean Change From Baseline in Insomnia Severity Index Total Score Averaged Over the 12 Week Double Blind Study Period

Change from baseline in the Insomnia Severity Index Total Score which ranges from 0-28. Lower scores represent better sleep. The change is calculated as the average over the double blind period (average of post-dose values from weeks 3,6,9,12) minus the baseline value.

Change from baseline in the Insomnia Severity Index Total Score which ranges from 0-28. Lower scores represent better sleep. The change is calculated as time point value minus the baseline value.

The Insomnia Severity Index Total Score ranges from 0-28. Lower scores represent better sleep. Mean values are reported at baseline(week 0), double-blind phase(weeks 3,6,9,12), single-blind follow-up(week 14), non-drug treatment follow-up(week 16), and the average for the double-blind phase(average of weeks 3,6,9,12 values).

Physical component summary of Short Form-36 Scale measures subject's perception of their physical health, where the normal mean for general US population is 50.Scores above/below 50 represent better than/worse than the general US population. Higher scores represent better outcomes. Change is calculated as time point value minus baseline value.

This scale measures subject's perception of their physical health, where the normal mean for general US population is 50.Scores above/below 50 represent better/worse than general US population. Change calculated as time point value minus baseline value: baseline(week0), double-blind (weeks 6,12)and non-drug treatment follow-up(week16).

Mental component summary of Short Form-36 Scale measures subject's perception of their physical health, where the normal mean for general US population is 50. Scores above/below 50 represent better than/worse than the general US population. Higher scores represent better outcomes. Change is calculated as time point value minus baseline value.

This scale measures subject's perception of their physical health, where normal mean for general US population is 50. Scores above/below 50 represent better/worse than general US population. Change calculated: time point value minus baseline value. Mean values: baseline(week0), double-blind phase(weeks 6,12)& non-drug treatment follow-up(week 16).

Sheehan Disability Scale Total Score (range 0-30)measures subject's level of disability & includes: work/school, social life, family life/home responsibilities, days lost &days underproductive; higher scores represent higher degree of disability/impairment. Change is calculated as time point value minus baseline value.

Sheehan Disability Scale Total Score (range 0-30) measures subject's level of disability; includes work/school, social life, family life/home responsibilities, days lost, days underproductive; higher scores represent higher degree of disability/impairment. Mean values reported: baseline, double-blind(weeks 6,12)& follow-up(weeks 14,16).

Inclusion Criteria: Male and female subjects with primary chronic insomnia. Subject is otherwise in good general health, based on screening physical examination and medical history. Exclusion Criteria: Subject has recent history of known clinically significant abnormal laboratory findings.

Ancoli-Israel S, Krystal AD, McCall WV, Schaefer K, Wilson A, Claus R, Rubens R, Roth T. A 12-week, randomized, double-blind, placebo-controlled study evaluating the effect of eszopiclone 2 mg on sleep/wake function in older adults with primary and comorbid insomnia. Sleep. 2010 Feb;33(2):225-34. doi: 10.1093/sleep/33.2.225.