Study of Lemborexant for Irregular Sleep-Wake Rhythm Disorder and Mild to Moderate Alzheimer's Disease Dementia

NCT03001557 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: E2006-G000-2022017-003306-40
• Study Type: interventional
• Target: 63
• Locations: 3 countries
• Sites: 48

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.

Conditions

Irregular Sleep-Wake Rhythm Disorder

Keywords

Mild to Moderate Alzheimer's Disease Dementia; sleep; circadian rhythms

Outcome Measures

Primary Outcomes (48)

• Core Phase: Change From Baseline in Mean Actigraphy Sleep Efficiency (aSE) With Lemborexant Compared to Placebo During Week 1 of Treatment

  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.

  Baseline, Week 1

• Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 2 of Treatment

  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.

  Baseline, Week 2

• Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 3 of Treatment

  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.

  Baseline, Week 3

• Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 4 of Treatment

  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.

  Baseline, Week 4

• Core Phase: Change From Baseline in Mean Sleep Fragmentation Index (SFI) During Week 1 of Treatment

  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.

  Baseline, Week 1

• Core Phase: Change From Baseline in Mean SFI During Week 2 of Treatment

  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.

  Baseline, Week 2

• Core Phase: Change From Baseline in Mean SFI During Week 3 of Treatment

  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.

  Baseline, Week 3

• Core Phase: Change From Baseline in Mean SFI During Week 4 of Treatment

  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.

  Baseline, Week 4

• Core Phase: Change From Baseline in the Mean Duration of Wake Bouts (aMeanDurWB) During Week 1 of Treatment

  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.

  Baseline, Week 1

• Core Phase: Change From Baseline in the aMeanDurWB During Week 2 of Treatment

  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.

  Baseline, Week 2

• Core Phase: Change From Baseline in the aMeanDurWB During Week 3 of Treatment

  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.

  Baseline, Week 3

• Core Phase: Change From Baseline in the aMeanDurWB During Week 4 of Treatment

  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.

  Baseline, Week 4

• Core Phase: Change From Baseline in Mean Actigraphy Wake Efficiency (aWE) During Week 1 of Treatment

  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.

  Baseline, Week 1

• Core Phase: Change From Baseline in Mean aWE During Week 2 of Treatment

  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.

  Baseline, Week 2

• Core Phase: Change From Baseline in Mean aWE During Week 3 of Treatment

  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.

  Baseline, Week 3

• Core Phase: Change From Baseline in Mean aWE During Week 4 of Treatment

  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.

  Baseline, Week 4

• Core Phase: Change From Baseline in Mean Wake Fragmentation Index (WFI) During Week 1 of Treatment

  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.

  Baseline, Week 1

• Core Phase: Change From Baseline in Mean WFI During Week 2 of Treatment

  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.

  Baseline, Week 2

• Core Phase: Change From Baseline in Mean WFI During Week 3 of Treatment

  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.

  Baseline, Week 3

• Core Phase: Change From Baseline in Mean WFI During Week 4 of Treatment

  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.

  Baseline, Week 4

• Core Phase: Change From Baseline in the Mean Duration of Sleep Bouts (aMeanDurSB) During Week 1 of Treatment

  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.

  Baseline, Week 1

• Core Phase: Change From Baseline in the aMeanDurSB During Week 2 of Treatment

  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.

  Baseline, Week 2

• Core Phase: Change From Baseline in the aMeanDurSB During Week 3 of Treatment

  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.

  Baseline, Week 3

• Core Phase: Change From Baseline in the aMeanDurSB During Week 4 of Treatment

  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.

  Baseline, Week 4

• Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 1 of Treatment

  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.

  Baseline, Week 1

• Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 2 of Treatment

  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.

  Baseline, Week 2

• Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 3 of Treatment

  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.

  Baseline, Week 3

• Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 4 of Treatment

  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.

  Baseline, Week 4

• Core Phase: Change From Baseline in Mean Interdaily Stability (IS) Over Week 1 of Treatment

  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.

  Baseline, Week 1

• Core Phase: Change From Baseline in Mean IS Over Week 2 of Treatment

  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.

  Baseline, Week 2

• Core Phase: Change From Baseline in Mean IS Over Week 3 of Treatment

  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.

  Baseline, Week 3

• Core Phase: Change From Baseline in Mean IS Over Week 4 of Treatment

  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.

  Baseline, Week 4

• 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

  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.

  Baseline, Week 1

• Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 2 of Treatment

  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.

  Baseline, Week 2

• Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 3 of Treatment

  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.

  Baseline, Week 3

• Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 4 of Treatment

  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.

  Baseline, Week 4

• 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

  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.

  Baseline, Week 1

• Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 2 of Treatment

  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.

  Baseline, Week 2

• Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 3 of Treatment

  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.

  Baseline, Week 3

• Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 4 of Treatment

  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.

  Baseline, Week 4

• Core Phase: Change From Baseline in Amplitude of the Rest-activity Rhythm (AMP) Over Week 1 of Treatment

  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.

  Baseline, Week 1

• Core Phase: Change From Baseline in AMP Over Week 2 of Treatment

  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.

  Baseline, Week 2

• Core Phase: Change From Baseline in AMP Over Week 3 of Treatment

  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.

  Baseline, Week 3

• Core Phase: Change From Baseline in AMP Over Week 4 of Treatment

  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.

  Baseline, Week 4

• Core Phase: Change From Baseline in Relative Amplitude in the Rest-activity Rhythm (RA) Over Week 1 of Treatment

  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.

  Baseline, Week 1

• Core Phase: Change From Baseline in RA Over Week 2 of Treatment

  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.

  Baseline, Week 2

• Core Phase: Change From Baseline in RA Over Week 3 of Treatment

  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.

  Baseline, Week 3

• Core Phase: Change From Baseline in RA Over Week 4 of Treatment

  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.

  Baseline, Week 4

Other Outcomes (5)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)

• Core Phase: Number of Participants in Each Category With Clinician's Global Impression of Change-Irregular Sleep-Wake Rhythm Disorder (CGIC-ISWRD) Global Score at Day 29

  Day 29

• Core Phase: Change From Baseline in the Neuropsychiatric Inventory (NPI-10) Total Score at Day 29

  Baseline, Day 29

Study Arms (5)

Lemborexant 2.5 milligrams (mg)

EXPERIMENTAL

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.

Drug: Lemborexant 2.5 mg; Drug: Lemborexant-matched placebo

Lemborexant 5 mg

EXPERIMENTAL

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.

Drug: Lemborexant 5 mg; Drug: Lemborexant-matched placebo

Lemborexant 10 mg

EXPERIMENTAL

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.

Drug: Lemborexant 10 mg; Drug: Lemborexant-matched placebo

Lemborexant 15 mg

EXPERIMENTAL

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.

Drug: Lemborexant 10 mg; Drug: Lemborexant 15 mg

Lemborexant-matched placebo

PLACEBO COMPARATOR

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.

Drug: Lemborexant-matched placebo

Interventions

Lemborexant 2.5 mg DRUG

Lemborexant 2.5 mg tablets

Lemborexant 2.5 milligrams (mg)

Lemborexant 5 mg DRUG

Lemborexant 5 mg tablets

Lemborexant 5 mg

Lemborexant 10 mg DRUG

Lemborexant 10 mg tablets

Lemborexant 10 mg; Lemborexant 15 mg

Lemborexant 15 mg DRUG

Lemborexant 5 mg and 10 mg tablets

Lemborexant 15 mg

Lemborexant-matched placebo DRUG

Lemborexant-matched placebo tablets

Lemborexant 10 mg; Lemborexant 2.5 milligrams (mg); Lemborexant 5 mg; Lemborexant-matched placebo

Eligibility Criteria

• Age: 60 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age 60 to 90 years at the time of informed consent
• Able to provide informed consent. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required in accordance with local laws, regulations and customs, and the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations).
• Documentation of diagnosis with Alzheimer's disease dementia (AD-D) on the basis of the National Institute on Aging/Alzheimer's Association Diagnostic Guidelines
• Mini Mental State Examination 10 to 26 at Screening
• Meets criteria for Circadian Rhythm Sleep Disorder, Irregular Sleep-Wake Type (Diagnostic and Statistical Manual of Mental Disorders - 5th edition) and the 10th revision of the International Classification of Diseases, as follows: Complaint by the participant or caregiver of difficulty sleeping during the night and/or excessive daytime sleepiness associated with multiple irregular sleep bouts during a 24-hour period
• Frequency of complaint of sleep and wake fragmentation ≥3 days per week
• Duration of complaint of sleep and wake fragmentation ≥3 months
• During the Screening Period, mean actigraphy-derived sleep efficiency (aSE) \<87.5% within the defined nocturnal sleep period and mean actigraphy-derived wake efficiency (aWE) \<87.5% during the defined wake period
• Confirmation by actigraphy of a combination of sleep bouts of \>10 minutes during the wake period plus wake bouts of \>10 minutes during the sleep period, totaling at least 4 bouts per 24 hours period, ≥ 3 days per week
• Ambulatory and living in the community or in a residence not classified as a skilled nursing facility (an assisted living facility with separate living quarters where participants and their caregivers reside is acceptable)
• Willing not to start a behavioral or other treatment program for sleep or wake difficulties and not to start a new treatment for other symptoms of AD-D during participation in the study
• Has a reliable and competent caregiver (or caregiver and informants) who can accompany the participant to study visits, administer study medication on a nightly basis and provide information on the status of the participant
• For participants taking a cholinesterase inhibitor and/or memantine, dosing regimen must have been stable for at least 3 months
• Completed the Core Study (End of Study \[EOS\] Visit). Participants who participated in the Core Study and completed the EOS Visit within 30 days may return to participate in the Extension Phase as long as there are no contraindications due to ongoing adverse events or prohibited medications.
• Able to provide informed consent

You may not qualify if:

• 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
• Known to be human immunodeficiency virus positive
• Active viral hepatitis (B or C) as demonstrated by positive serology at Screening
• A prolonged QTcF interval (QTcF \>450 milliseconds\[ms\]) as demonstrated by a repeated electrocardiogram (ECG) at Screening (repeated only if initial ECG indicates a QTcF interval \>450 ms) (participants with evidence of bundle branch block are not excluded if the block is not clinically significant, as documented by the investigator in the source document)
• Current evidence of clinically significant disease that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
• Any history of a medical or psychiatric condition other than Alzheimer's Disease dementia that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments

Sponsors & Collaborators

• Eisai Inc.: lead
• Purdue Pharma LP: collaborator

Study Sites (48)

Facility #1

Little Rock, Arkansas, 72205, United States

Location

Facility #1

Rogers, Arkansas, 72758, United States

Location

Facility #1

Costa Mesa, California, 92626, United States

Location

Facility #1

Fullerton, California, 92835, United States

Location

Facility #1

Glendale, California, 91206, United States

Location

Facility #1

Irvine, California, 92614, United States

Location

Facility #1

Irvine, California, 92618, United States

Location

Facility #1

La Jolla, California, 92037-0949, United States

Location

Facility #1

San Diego, California, 92103, United States

Location

Facility #1

Santa Monica, California, 90404, United States

Location

Facility #1

Bradenton, Florida, 34205, United States

Location

Facility #1

Brandon, Florida, 33511, United States

Location

Facility #1

Brooksville, Florida, 34601, United States

Location

Facility #1

Hallandale, Florida, 33009, United States

Location

Facility #1

Miami, Florida, 33137, United States

Location

Facility #1

Miami, Florida, 33165, United States

Location

Facility #1

Miami Lakes, Florida, 33014, United States

Location

Facility #1

Miami Springs, Florida, 33016, United States

Location

Facility #1

Orlando, Florida, 32806, United States

Location

Facility #2

Orlando, Florida, 32806, United States

Location

Facility #1

Sunrise, Florida, 33351, United States

Location

Facility #2

Tampa, Florida, 33613, United States

Location

Facility #1

Atlanta, Georgia, 30331, United States

Location

Facility #1

Columbus, Georgia, 31909, United States

Location

Facility #1

Macon, Georgia, 31201, United States

Location

Facility #1

Wichita, Kansas, 67207, United States

Location

Facility #1

Belmont, Massachusetts, 02478, United States

Location

Nevada Senior Services (NSS) Adult Day Care Center

Henderson, Nevada, United States

Location

Facility #1

Las Vegas, Nevada, 89104, United States

Location

Facility #1

Toms River, New Jersey, 08755, United States

Location

Facility #2

Toms River, New Jersey, 08755, United States

Location

Facility #1

Charlotte, North Carolina, 28270, United States

Location

Facility #2

Durham, North Carolina, 27705, United States

Location

Facility #1

Raleigh, North Carolina, 27612, United States

Location

Facility #1

Norristown, Pennsylvania, 19401, United States

Location

Facility #1

Willow Grove, Pennsylvania, 19090, United States

Location

Facility #1

Columbia, South Carolina, 29203, United States

Location

Eisai Trial Site #1

Nagoya, Aichi-ken, 451-8511, Japan

Location

Eisai Trial Site #1

Fujisawa, Kanagawa, 251-0038, Japan

Location

Eisai Trial Site #1

Kawasaki-shi, Kanagawa, 210-0852, Japan

Location

Eisai Trial Site #1

Wako, Saitama, 351-0111, Japan

Location

Eisai Trial Site #1

Kodaira, Tokyo, 187-8551, Japan

Location

Eisai Trial Site #1

Setagaya City, Tokyo, 156-0041, Japan

Location

Eisai Trial Site #1

Shinjuku, Tokyo, 169-0073, Japan

Location

Eisai Trial Site #1

Tachikawa-shi, Tokyo, 190-8531, Japan

Location

Brighton and Sussex Medical School

Brighton, East Sussex, BN1 9PX, United Kingdom

Location

Cognitive Treatment and Research Unit

Crowborough, East Sussex, TN6 1NY, United Kingdom

Location

University of Edinburgh - PPDS

Edinburgh, EH1 64UX, United Kingdom

Location

MeSH Terms

Interventions

lemborexant

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_medinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2016
• First Posted: December 23, 2016
• Study Start: December 20, 2016
• Primary Completion: July 26, 2018
• Study Completion: April 17, 2020
• Last Updated: May 17, 2021
• Results First Posted: January 14, 2020

Record last verified: 2021-04

Locations

GB (3); US (37); JP (8)