A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study With Open-Label Extension Phase of the Efficacy and Safety of Lemborexant in Subjects With Irregular Sleep-Wake Rhythm Disorder and Mild to Moderate Alzheimer's Disease Dementia
Overview
- Phase
- Phase 2
- Intervention
- Lemborexant 2.5 mg
- Conditions
- Irregular Sleep-Wake Rhythm Disorder
- Sponsor
- Eisai Inc.
- Enrollment
- 63
- Locations
- 7
- Primary Endpoint
- Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 3 of Treatment
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This study will be conducted to determine the dose response of lemborexant (LEM) on the change from baseline in actigraphy-derived sleep-related parameters, wake-related parameters, and circadian-rhythm related parameters. Following the eligibility screening period, eligible participants will be assigned at random to 1 of 4 doses of LEM or to placebo for 4 weeks. After a 2-week follow-up period, eligible participants may enter an open-label extension period for up to 30 months or until the program discontinuation.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •A diagnosis of vascular dementia, dementia following multiple strokes, or any synucleinopathy / Lewy body disorder. This includes Dementia with Lewy Bodies and Parkinson's disease with or without dementia.
- •A current diagnosis of moderate to severe obstructive sleep apnea (OSA) or central sleep apnea, or current use of continuous positive airways pressure even if mild severity of OSA, restless legs syndrome, periodic limb movement disorder (with awakenings), or narcolepsy
- •An Apnea-Hypopnea Index or equivalent ≥15 events/hour on diagnostic sleep study conducted prior to Baseline or within 6 months of Screening
- •A clinically significant movement disorder that would affect the differentiation of sleep and wake by the actigraphy analytic algorithm
- •Current symptoms or history during the past year of Rapid Eye Movement Behavior Disorder or sleep-related violent behavior
- •Probable Major Depression, as evidenced by score \>10 on the Cornell Scale for Depression in Dementia at Screening
- •Unable to tolerate wearing the actigraph. At a minimum, participants must be able to wear the actigraph for 5 complete days out of 7 days' data. A day will be considered complete as long as data from 90% of the 24-hour period are able to be scored.
- •Excessive caffeine use that in the opinion of the investigator contributes to the participant's Irregular Sleep-Wake Rhythm Disorder (ISWRD)
- •History of drug or alcohol dependency or abuse within approximately the previous 2 years
- •Reports habitually consuming more than 14 drinks containing alcohol per week or habitually consumes alcohol within 3 hours before bedtime and unwilling to limit alcohol intake to 2 or fewer drinks per day or forego having alcohol within 3 hours before bedtime for the duration of his/her participation in the study
Arms & Interventions
Lemborexant 2.5 milligrams (mg)
Participants will take one lemborexant 2.5 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.
Intervention: Lemborexant 2.5 mg
Lemborexant 2.5 milligrams (mg)
Participants will take one lemborexant 2.5 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.
Intervention: Lemborexant-matched placebo
Lemborexant 5 mg
Participants will take one lemborexant 5 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.
Intervention: Lemborexant 5 mg
Lemborexant 5 mg
Participants will take one lemborexant 5 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.
Intervention: Lemborexant-matched placebo
Lemborexant 10 mg
Participants will take one lemborexant 10 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.
Intervention: Lemborexant 10 mg
Lemborexant 10 mg
Participants will take one lemborexant 10 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.
Intervention: Lemborexant-matched placebo
Lemborexant 15 mg
Participants will take one lemborexant 5 mg tablet and one lemborexant 10 mg tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.
Intervention: Lemborexant 10 mg
Lemborexant 15 mg
Participants will take one lemborexant 5 mg tablet and one lemborexant 10 mg tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.
Intervention: Lemborexant 15 mg
Lemborexant-matched placebo
Participants will take two lemborexant-matched placebo tablets orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.
Intervention: Lemborexant-matched placebo
Outcomes
Primary Outcomes
Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 3 of Treatment
Time Frame: Baseline, Week 3
aSE was defined as the percentage of time spent in bed nocturnal sleeping, as measured by actigraphy. Sleep efficiency was calculated as the total duration of sleep epochs during the predefined 8-hour nocturnal sleep period divided by 8 hours and multiplied by 100. Higher values were better. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average third 7 nights of treatment was reported.
Core Phase: Change From Baseline in the aMeanDurSB During Week 3 of Treatment
Time Frame: Baseline, Week 3
aMeanDurSB was defined as an average duration of all sleep bouts that occurred during the 16 hours outside of the predefined nocturnal sleep period. The sleep bout was defined as the continuous sleep of 10 minutes or longer. Lower values were better. aMeanDurSB was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average third 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean IS Over Week 2 of Treatment
Time Frame: Baseline, Week 2
IS gives an indication of the stability of the sleep-wake rhythm across days, and varies from zero (low stability) to 1 (high stability). IS was derived by the ratio between the variance of the average 24-hour pattern around the mean and the overall variance. Higher values indicated stable rhythm. IS was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 2 of Treatment
Time Frame: Baseline, Week 2
aSE was defined as the percentage of time spent in bed nocturnal sleeping, as measured by actigraphy. Sleep efficiency was calculated as the total duration of sleep epochs during the predefined 8-hour nocturnal sleep period divided by 8 hours and multiplied by 100. Higher values were better. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in the aMeanDurWB During Week 3 of Treatment
Time Frame: Baseline, Week 3
aMeanDurWB was defined as an average duration of all wake bouts that occurred during the defined nocturnal predefined sleep period. The wake bout was defined as continuous wake of 10 minutes or longer. Lower values were better. aMeanDurWB was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average third 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 4 of Treatment
Time Frame: Baseline, Week 4
aSE was defined as the percentage of time spent in bed nocturnal sleeping, as measured by actigraphy. Sleep efficiency was calculated as the total duration of sleep epochs during the predefined 8-hour nocturnal sleep period divided by 8 hours and multiplied by 100. Higher values were better. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average last 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean SFI During Week 2 of Treatment
Time Frame: Baseline, Week 2
The SFI was defined as the sum of a MI and a FI during the logged sleep period. The MI was equal to the epochs of wake per TBI multiplied by 100. The FI was equal to the number \<=1-minute periods of immobility/total number of periods of immobility of all durations during the defined nocturnal sleep period multiplied by 100. Value ranges from 0-100% (lower values were better). SFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean SFI During Week 3 of Treatment
Time Frame: Baseline, Week 3
The SFI was defined as the sum of a MI and a FI during the logged sleep period. The MI was equal to the epochs of wake per TBI multiplied by 100. The FI was equal to the number \<=1-minute periods of immobility/total number of periods of immobility of all durations during the defined nocturnal sleep period multiplied by 100. Value ranges from 0-100% (lower values were better). SFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average third 7 nights of treatment was reported.
Core Phase: Change From Baseline in the aMeanDurWB During Week 2 of Treatment
Time Frame: Baseline, Week 2
aMeanDurWB was defined as an average duration of all wake bouts that occurred during the defined nocturnal predefined sleep period. The wake bout was defined as continuous wake of 10 minutes or longer. Lower values were better. aMeanDurWB was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean Actigraphy Sleep Efficiency (aSE) With Lemborexant Compared to Placebo During Week 1 of Treatment
Time Frame: Baseline, Week 1
aSE was defined as the percentage of time spent in bed nocturnal sleeping, as measured by actigraphy. Sleep efficiency was calculated as the total duration of sleep epochs during the predefined 8-hour nocturnal sleep period divided by 8 hours and multiplied by 100. Higher values were better. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean Sleep Fragmentation Index (SFI) During Week 1 of Treatment
Time Frame: Baseline, Week 1
The SFI was defined as the sum of a movement index (MI) and a fragmentation index (FI) during the logged sleep period. The MI was equal to the epochs of wake per time in bed (TBI) multiplied by 100. The FI was equal to the number of less than or equal to (\<=) 1-minute periods of immobility/total number of periods of immobility of all durations during the defined nocturnal sleep period multiplied by 100. Value ranges from 0-100 percent (%) (lower values were better). SFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean SFI During Week 4 of Treatment
Time Frame: Baseline, Week 4
The SFI was defined as the sum of a MI and a FI during the logged sleep period. The MI was equal to the epochs of wake per TBI multiplied by 100. The FI was equal to the number \<=1-minute periods of immobility/total number of periods of immobility of all durations during the defined nocturnal sleep period multiplied by 100. Value ranges from 0-100% (lower values were better). SFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average last 7 nights of treatment was reported.
Core Phase: Change From Baseline in the Mean Duration of Wake Bouts (aMeanDurWB) During Week 1 of Treatment
Time Frame: Baseline, Week 1
aMeanDurWB was defined as an average duration of all wake bouts that occurred during the defined nocturnal predefined sleep period. The wake bout was defined as continuous wake of 10 minutes or longer. Lower values were better. aMeanDurWB was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean aWE During Week 4 of Treatment
Time Frame: Baseline, Week 4
aWE was defined as the percentage of time spent awake in bed during defined wake period, as measured by actigraphy. Wake efficiency was calculated as the total duration of wake epochs during 16 hours outside of the predefined sleep period divided by 16 hours and multiplied by 100. Higher values were better. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average last 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean Wake Fragmentation Index (WFI) During Week 1 of Treatment
Time Frame: Baseline, Week 1
The WFI were calculated as the sum of an immobility index (II) and a FI during the logged wake period. The II was equal to the epochs of immobility per the 16 hours outside of the defined sleep period multiplied by 100. The FI was equal to the number of \<=1-minute periods of mobility/total number of periods of mobility the 16 hours outside of the defined sleep period multiplied by 100. Value ranges from 0-100 percent (lower values were better). The WFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in the aMeanDurWB During Week 4 of Treatment
Time Frame: Baseline, Week 4
aMeanDurWB was defined as an average duration of all wake bouts that occurred during the defined nocturnal predefined sleep period. The wake bout was defined as continuous wake of 10 minutes or longer. Lower values were better. aMeanDurWB was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average last 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean Actigraphy Wake Efficiency (aWE) During Week 1 of Treatment
Time Frame: Baseline, Week 1
aWE was defined as the percentage of time spent awake in bed during defined wake period, as measured by actigraphy. Wake efficiency was calculated as the total duration of wake epochs during 16 hours outside of the predefined sleep period divided by 16 hours and multiplied by 100. Higher values were better. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean aWE During Week 2 of Treatment
Time Frame: Baseline, Week 2
aWE was defined as the percentage of time spent awake in bed during defined wake period, as measured by actigraphy. Wake efficiency was calculated as the total duration of wake epochs during 16 hours outside of the predefined sleep period divided by 16 hours and multiplied by 100. Higher values were better. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in the Mean Duration of Sleep Bouts (aMeanDurSB) During Week 1 of Treatment
Time Frame: Baseline, Week 1
aMeanDurSB was defined as an average duration of all sleep bouts that occurred during the 16 hours outside of the predefined nocturnal sleep period. The sleep bout was defined as the continuous sleep of 10 minutes or longer. Lower values were better. aMeanDurSB was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean aWE During Week 3 of Treatment
Time Frame: Baseline, Week 3
aWE was defined as the percentage of time spent awake in bed during defined wake period, as measured by actigraphy. Wake efficiency was calculated as the total duration of wake epochs during 16 hours outside of the predefined sleep period divided by 16 hours and multiplied by 100. Higher values were better. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average third 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean WFI During Week 2 of Treatment
Time Frame: Baseline, Week 2
The WFI were calculated as the sum of an II and a FI during the logged wake period. The II was equal to the epochs of immobility per the 16 hours outside of the defined sleep period multiplied by 100. The FI was equal to the number of \<=1-minute periods of mobility/total number of periods of mobility the 16 hours outside of the defined sleep period multiplied by 100. Value ranges from 0-100% (lower values were better). The WFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in the aMeanDurSB During Week 4 of Treatment
Time Frame: Baseline, Week 4
aMeanDurSB was defined as an average duration of all sleep bouts that occurred during the 16 hours outside of the predefined nocturnal sleep period. The sleep bout was defined as the continuous sleep of 10 minutes or longer. Lower values were better. aMeanDurSB was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average last 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 2 of Treatment
Time Frame: Baseline, Week 2
Intradaily variability gives an indication of ISWRD by quantifying the number and strength of transitions between rest and activity bouts, derived by the ratio of the mean squares of the difference between all successive hours (first derivative) and the mean squares around the grand mean (overall variance). The variable has a theoretical range of 0 to 2, with higher values indicating higher fragmentation. Intradaily variability was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in Average Activity Counts Across Least Active 5-hour Period (L5) Per 24-Hour Period Over Week 1 of Treatment
Time Frame: Baseline, Week 1
L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. This value provides an indication of how restful (inactive) and regular the sleep periods are. L5 was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 4 of Treatment
Time Frame: Baseline, Week 4
M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. M10 was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average last 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean WFI During Week 3 of Treatment
Time Frame: Baseline, Week 3
The WFI were calculated as the sum of an II and a FI during the logged wake period. The II was equal to the epochs of immobility per the 16 hours outside of the defined sleep period multiplied by 100. The FI was equal to the number of \<=1-minute periods of mobility/total number of periods of mobility the 16 hours outside of the defined sleep period multiplied by 100. Value ranges from 0-100% (lower values were better). The WFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average third 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean WFI During Week 4 of Treatment
Time Frame: Baseline, Week 4
The WFI were calculated as the sum of an II and a FI during the logged wake period. The II was equal to the epochs of immobility per the 16 hours outside of the defined sleep period multiplied by 100. The FI was equal to the number of \<=1-minute periods of mobility/total number of periods of mobility the 16 hours outside of the defined sleep period multiplied by 100. Value ranges from 0-100% (lower values were better). The WFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average last 7 nights of treatment was reported.
Core Phase: Change From Baseline in the aMeanDurSB During Week 2 of Treatment
Time Frame: Baseline, Week 2
aMeanDurSB was defined as an average duration of all sleep bouts that occurred during the 16 hours outside of the predefined nocturnal sleep period. The sleep bout was defined as the continuous sleep of 10 minutes or longer. Lower values were better. aMeanDurSB was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 1 of Treatment
Time Frame: Baseline, Week 1
Intradaily variability gives an indication of irregular sleep-wake rhythm disorder (ISWRD) by quantifying the number and strength of transitions between rest and activity bouts, derived by the ratio of the mean squares of the difference between all successive hours (first derivative) and the mean squares around the grand mean (overall variance). The variable has a theoretical range of 0 to 2, with higher values indicating higher fragmentation. Intradaily variability was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 4 of Treatment
Time Frame: Baseline, Week 4
Intradaily variability gives an indication of ISWRD by quantifying the number and strength of transitions between rest and activity bouts, derived by the ratio of the mean squares of the difference between all successive hours (first derivative) and the mean squares around the grand mean (overall variance). The variable has a theoretical range of 0 to 2, with higher values indicating higher fragmentation. Intradaily variability was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average last 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean IS Over Week 3 of Treatment
Time Frame: Baseline, Week 3
IS gives an indication of the stability of the sleep-wake rhythm across days, and varies from zero (low stability) to 1 (high stability). IS was derived by the ratio between the variance of the average 24-hour pattern around the mean and the overall variance. Higher values indicated stable rhythm. IS was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average third 7 nights of treatment was reported.
Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 2 of Treatment
Time Frame: Baseline, Week 2
M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. M10 was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in Amplitude of the Rest-activity Rhythm (AMP) Over Week 1 of Treatment
Time Frame: Baseline, Week 1
AMP was amplitude of rest-activity rhythm calculated as the difference between M10 and L5. L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. AMP was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 3 of Treatment
Time Frame: Baseline, Week 3
Intradaily variability gives an indication of ISWRD by quantifying the number and strength of transitions between rest and activity bouts, derived by the ratio of the mean squares of the difference between all successive hours (first derivative) and the mean squares around the grand mean (overall variance). The variable has a theoretical range of 0 to 2, with higher values indicating higher fragmentation. Intradaily variability was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average third 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean Interdaily Stability (IS) Over Week 1 of Treatment
Time Frame: Baseline, Week 1
IS gives an indication of the stability of the sleep-wake rhythm across days, and varies from zero (low stability) to 1 (high stability). IS was derived by the ratio between the variance of the average 24-hour pattern around the mean and the overall variance. Higher values indicated stable rhythm. IS was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean IS Over Week 4 of Treatment
Time Frame: Baseline, Week 4
IS gives an indication of the stability of the sleep-wake rhythm across days, and varies from zero (low stability) to 1 (high stability). IS was derived by the ratio between the variance of the average 24-hour pattern around the mean and the overall variance. Higher values indicated stable rhythm. IS was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average last 7 nights of treatment was reported.
Core Phase: Change From Baseline in AMP Over Week 3 of Treatment
Time Frame: Baseline, Week 3
AMP was amplitude of rest-activity rhythm calculated as the difference between M10 and L5. L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. AMP was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average third 7 nights of treatment was reported.
Core Phase: Change From Baseline in RA Over Week 3 of Treatment
Time Frame: Baseline, Week 3
RA was relative amplitude of the rest-activity rhythm calculated as the difference between M10 and L5 divided by M10 plus L5. L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. RA was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average third 7 nights of treatment was reported.
Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 2 of Treatment
Time Frame: Baseline, Week 2
L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. This value provides an indication of how restful (inactive) and regular the sleep periods are. L5 was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 4 of Treatment
Time Frame: Baseline, Week 4
L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. This value provides an indication of how restful (inactive) and regular the sleep periods are. L5 was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average last 7 nights of treatment was reported.
Core Phase: Change From Baseline in the Average Activity Count During the Most Active 10-hour Period (M10) Per 24-Hour Period Over Week 1 of Treatment
Time Frame: Baseline, Week 1
M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. M10 was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 3 of Treatment
Time Frame: Baseline, Week 3
M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. M10 was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average third 7 nights of treatment was reported.
Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 3 of Treatment
Time Frame: Baseline, Week 3
L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. This value provides an indication of how restful (inactive) and regular the sleep periods are. L5 was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average third 7 nights of treatment was reported.
Core Phase: Change From Baseline in AMP Over Week 2 of Treatment
Time Frame: Baseline, Week 2
AMP was amplitude of rest-activity rhythm calculated as the difference between M10 and L5. L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. AMP was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in AMP Over Week 4 of Treatment
Time Frame: Baseline, Week 4
AMP was amplitude of rest-activity rhythm calculated as the difference between M10 and L5. L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. AMP was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average last 7 nights of treatment was reported.
Core Phase: Change From Baseline in Relative Amplitude in the Rest-activity Rhythm (RA) Over Week 1 of Treatment
Time Frame: Baseline, Week 1
RA was relative amplitude of the rest-activity rhythm calculated as the difference between M10 and L5 divided by M10 plus L5. L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. RA was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in RA Over Week 2 of Treatment
Time Frame: Baseline, Week 2
RA was relative amplitude of the rest-activity rhythm calculated as the difference between M10 and L5 divided by M10 plus L5. L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. RA was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in RA Over Week 4 of Treatment
Time Frame: Baseline, Week 4
RA was relative amplitude of the rest-activity rhythm calculated as the difference between M10 and L5 divided by M10 plus L5. L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. RA was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average last 7 nights of treatment was reported.