Phase 2
N=63
Study of Lemborexant for Irregular Sleep-Wake Rhythm Disorder and Mild to Moderate Alzheimer's Disease Dementia
Irregular Sleep-Wake Rhythm Disorder
Bottom Line
View on ClinicalTrials.gov: NCT03001557 ↗Enrolled (actual)
63
Serious AEs
4.6%
Results posted
Jan 2020
Primary outcome: Primary: Core Phase: Change From Baseline in Mean Actigraphy Sleep Efficiency (aSE) With Lemborexant Compared to Placebo During Week 1 of Treatment — 76.34; 77.64; 78.45; 76.38 percentage of sleep time
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Lemborexant 2.5 mg (Drug); Lemborexant 5 mg (Drug); Lemborexant 10 mg (Drug); Lemborexant 15 mg (Drug); Lemborexant-matched placebo (Drug)
- Age
- Adult, Older Adult · 60+ yrs
- Sex
- All
- Sponsor
- Eisai Inc.
- Primary completion
- Jul 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Core Phase: Change From Baseline in Mean Actigraphy Sleep Efficiency (aSE) With Lemborexant Compared to Placebo During Week 1 of Treatment |
76.34; 77.64; 78.45; 76.38; 77.35; 0.14 | — |
| PRIMARY Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 2 of Treatment |
76.34; 77.64; 78.45; 76.38; 77.35; -1.31 | — |
| PRIMARY Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 3 of Treatment |
76.34; 77.64; 78.45; 76.38; 77.35; -0.30 | — |
| PRIMARY Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 4 of Treatment |
76.34; 77.64; 78.45; 76.38; 77.35; -0.78 | 0.1099 |
| PRIMARY Core Phase: Change From Baseline in Mean Sleep Fragmentation Index (SFI) During Week 1 of Treatment |
58.51; 53.87; 50.07; 54.75; 54.78; -1.43 | — |
| PRIMARY Core Phase: Change From Baseline in Mean SFI During Week 2 of Treatment |
58.51; 53.87; 50.07; 54.75; 54.78; 2.52 | — |
| PRIMARY Core Phase: Change From Baseline in Mean SFI During Week 3 of Treatment |
58.51; 53.87; 50.07; 54.75; 54.78; -3.30 | — |
| PRIMARY Core Phase: Change From Baseline in Mean SFI During Week 4 of Treatment |
58.51; 53.87; 50.07; 54.75; 54.78; -1.39 | 0.1582 |
| PRIMARY Core Phase: Change From Baseline in the Mean Duration of Wake Bouts (aMeanDurWB) During Week 1 of Treatment |
20.32; 20.40; 20.62; 21.89; 21.94; -1.65 | — |
| PRIMARY Core Phase: Change From Baseline in the aMeanDurWB During Week 2 of Treatment |
20.32; 20.40; 20.62; 21.89; 21.94; -0.32 | — |
| PRIMARY Core Phase: Change From Baseline in the aMeanDurWB During Week 3 of Treatment |
20.32; 20.40; 20.62; 21.89; 21.94; -2.88 | — |
| PRIMARY Core Phase: Change From Baseline in the aMeanDurWB During Week 4 of Treatment |
20.32; 20.40; 20.62; 21.89; 21.94; -1.26 | 0.3966 |
| PRIMARY Core Phase: Change From Baseline in Mean Actigraphy Wake Efficiency (aWE) During Week 1 of Treatment |
69.74; 70.57; 72.53; 67.19; 70.67; 0.59 | — |
| PRIMARY Core Phase: Change From Baseline in Mean aWE During Week 2 of Treatment |
69.74; 70.57; 72.53; 67.19; 70.67; 2.14 | — |
| PRIMARY Core Phase: Change From Baseline in Mean aWE During Week 3 of Treatment |
69.74; 70.57; 72.53; 67.19; 70.67; 1.64 | — |
| PRIMARY Core Phase: Change From Baseline in Mean aWE During Week 4 of Treatment |
69.74; 70.57; 72.53; 67.19; 70.67; 2.03 | 0.1777 |
| PRIMARY Core Phase: Change From Baseline in Mean Wake Fragmentation Index (WFI) During Week 1 of Treatment |
92.43; 85.72; 86.53; 94.76; 87.96; -0.14 | — |
| PRIMARY Core Phase: Change From Baseline in Mean WFI During Week 2 of Treatment |
92.43; 85.72; 86.53; 94.76; 87.96; -3.76 | — |
| PRIMARY Core Phase: Change From Baseline in Mean WFI During Week 3 of Treatment |
92.43; 85.72; 86.53; 94.76; 87.96; -1.65 | — |
| PRIMARY Core Phase: Change From Baseline in Mean WFI During Week 4 of Treatment |
92.43; 85.72; 86.53; 94.76; 87.96; -3.01 | 0.1991 |
| PRIMARY Core Phase: Change From Baseline in the Mean Duration of Sleep Bouts (aMeanDurSB) During Week 1 of Treatment |
18.36; 20.65; 23.13; 19.84; 23.30; 2.15 | — |
| PRIMARY Core Phase: Change From Baseline in the aMeanDurSB During Week 2 of Treatment |
18.36; 20.65; 23.13; 19.84; 23.30; 0.25 | — |
| PRIMARY Core Phase: Change From Baseline in the aMeanDurSB During Week 3 of Treatment |
18.36; 20.65; 23.13; 19.84; 23.30; -0.14 | — |
| PRIMARY Core Phase: Change From Baseline in the aMeanDurSB During Week 4 of Treatment |
18.36; 20.65; 23.13; 19.84; 23.30; 1.00 | 0.9599 |
| PRIMARY Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 1 of Treatment |
1.10; 0.90; 0.98; 1.10; 1.03; -0.01 | — |
| PRIMARY Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 2 of Treatment |
1.10; 0.90; 0.98; 1.10; 1.03; -0.05 | — |
| PRIMARY Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 3 of Treatment |
1.10; 0.90; 0.98; 1.10; 1.03; -0.06 | — |
| PRIMARY Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 4 of Treatment |
1.10; 0.90; 0.98; 1.10; 1.03; -0.10 | 0.2421 |
| PRIMARY Core Phase: Change From Baseline in Mean Interdaily Stability (IS) Over Week 1 of Treatment |
0.45; 0.47; 0.49; 0.46; 0.41; 0.04 | — |
| PRIMARY Core Phase: Change From Baseline in Mean IS Over Week 2 of Treatment |
0.45; 0.47; 0.49; 0.46; 0.41; 0.06 | — |
| PRIMARY Core Phase: Change From Baseline in Mean IS Over Week 3 of Treatment |
0.45; 0.47; 0.49; 0.46; 0.41; 0.03 | — |
| PRIMARY Core Phase: Change From Baseline in Mean IS Over Week 4 of Treatment |
0.45; 0.47; 0.49; 0.46; 0.41; 0.02 | 0.2991 |
| PRIMARY 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 |
1163.5; 1266.4; 1163.2; 1257.1; 1490.4; 200.9 | — |
| PRIMARY Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 2 of Treatment |
1163.5; 1266.4; 1163.2; 1257.1; 1490.4; 85.8 | — |
| PRIMARY Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 3 of Treatment |
1163.5; 1266.4; 1163.2; 1257.1; 1490.4; 299.2 | — |
| PRIMARY Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 4 of Treatment |
1163.5; 1266.4; 1163.2; 1257.1; 1490.4; 293.1 | 0.0294 sig |
| PRIMARY 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 |
8560.4; 11567.0; 12158.1; 10662.1; 11460.5; 59.7 | — |
| PRIMARY Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 2 of Treatment |
8560.4; 11567.0; 12158.1; 10662.1; 11460.5; 232.7 | — |
| PRIMARY Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 3 of Treatment |
8560.4; 11567.0; 12158.1; 10662.1; 11460.5; 300.3 | — |
| PRIMARY Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 4 of Treatment |
8560.4; 11567.0; 12158.1; 10662.1; 11460.5; 1650.4 | 0.1162 |
| PRIMARY Core Phase: Change From Baseline in Amplitude of the Rest-activity Rhythm (AMP) Over Week 1 of Treatment |
7396.9; 10300.6; 10994.8; 9405.0; 9970.0; -141.1 | — |
| PRIMARY Core Phase: Change From Baseline in AMP Over Week 2 of Treatment |
7396.9; 10300.6; 10994.8; 9405.0; 9970.0; 146.8 | — |
| PRIMARY Core Phase: Change From Baseline in AMP Over Week 3 of Treatment |
7396.9; 10300.6; 10994.8; 9405.0; 9970.0; 1.1 | — |
| PRIMARY Core Phase: Change From Baseline in AMP Over Week 4 of Treatment |
7396.9; 10300.6; 10994.8; 9405.0; 9970.0; 1357.3 | 0.2984 |
| PRIMARY Core Phase: Change From Baseline in Relative Amplitude in the Rest-activity Rhythm (RA) Over Week 1 of Treatment |
0.73; 0.79; 0.82; 0.77; 0.76; -0.02 | — |
| PRIMARY Core Phase: Change From Baseline in RA Over Week 2 of Treatment |
0.73; 0.79; 0.82; 0.77; 0.76; -0.00 | — |
| PRIMARY Core Phase: Change From Baseline in RA Over Week 3 of Treatment |
0.73; 0.79; 0.82; 0.77; 0.76; -0.01 | — |
| PRIMARY Core Phase: Change From Baseline in RA Over Week 4 of Treatment |
0.73; 0.79; 0.82; 0.77; 0.76; -0.00 | 0.4638 |
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.
Eligibility Criteria
Inclusion Criteria (Core Study):
- 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) 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
Inclusion Criteria (Extension Phase):
- 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.
Inclusion Criteria for Caregivers:
- Able to provide informed consent
- Spends at least 10 hours per week with the participant
- Able to meet caregiver requirements
- Willing to provide information on himself/herself regarding sleep quality and caregiver Burden
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 mini
Data sourced from ClinicalTrials.gov (NCT03001557). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.