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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03001557
Recruitment Status : Active, not recruiting
First Posted : December 23, 2016
Last Update Posted : July 29, 2019
Sponsor:
Collaborator:
Purdue Pharma LP
Information provided by (Responsible Party):
Eisai Inc.

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 1 month. 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 has been discontinued.

Condition or disease Intervention/treatment Phase
Irregular Sleep-Wake Rhythm Disorder Drug: Lemborexant 2.5 mg Drug: Lemborexant 5 mg Drug: Lemborexant 10 mg Drug: Lemborexant 15 mg Drug: Lemborexant-matched placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 20, 2016
Actual Primary Completion Date : July 26, 2018
Estimated Study Completion Date : April 9, 2020


Arm Intervention/treatment
Experimental: 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.
Drug: Lemborexant 2.5 mg
Lemborexant 2.5 mg tablets

Experimental: 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.
Drug: Lemborexant 5 mg
Lemborexant 5 mg tablets

Experimental: 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.
Drug: Lemborexant 10 mg
Lemborexant 10 mg tablets

Experimental: 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.
Drug: Lemborexant 15 mg
Lemborexant 5 mg and 10 mg tablets

Placebo Comparator: 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.
Drug: Lemborexant-matched placebo
Lemborexant-matched placebo tablets




Primary Outcome Measures :
  1. Change From Baseline of Mean Sleep Fragmentation Index (SFI) During Week 1 of Treatment [ Time Frame: Baseline, Week 1 ]
  2. Change From Baseline of Mean SFI During Week 2 of Treatment [ Time Frame: Baseline, Week 2 ]
  3. Change From Baseline of Mean SFI During Week 3 of Treatment [ Time Frame: Baseline, Week 3 ]
  4. Change From Baseline of Mean SFI During Week 4 of Treatment [ Time Frame: Baseline, Week 4 ]
  5. Change From Baseline of Mean Wake Fragmentation Index (WFI) During Week 1 of Treatment [ Time Frame: Baseline, Week 1 ]
  6. Change From Baseline of Mean WFI During Week 2 of Treatment [ Time Frame: Baseline, Week 2 ]
  7. Change From Baseline of Mean WFI During Week 3 of Treatment [ Time Frame: Baseline, Week 3 ]
  8. Change From Baseline of Mean WFI During Week 4 of Treatment [ Time Frame: Baseline, Week 4 ]
  9. Change From Baseline in the Mean Duration of Sleep Bouts (aMeanDurSB) During Week 1 of Treatment [ Time Frame: Baseline, Week 1 ]
  10. Change From Baseline in the aMeanDurSB During Week 2 of Treatment [ Time Frame: Baseline, Week 2 ]
  11. Change From Baseline in the aMeanDurSB During Week 3 of Treatment [ Time Frame: Baseline, Week 3 ]
  12. Change From Baseline in the aMeanDurSB During Week 4 of Treatment [ Time Frame: Baseline, Week 4 ]
  13. Change From Baseline in the Mean Duration of Wake Bouts (aMeanDurWB) During Week 1 of Treatment [ Time Frame: Baseline, Week 1 ]
  14. Change From Baseline in the aMeanDurWB During Week 2 of Treatment [ Time Frame: Baseline, Week 2 ]
  15. Change From Baseline in the aMeanDurWB During Week 3 of Treatment [ Time Frame: Baseline, Week 3 ]
  16. Change From Baseline in the aMeanDurWB During Week 4 of Treatment [ Time Frame: Baseline, Week 4 ]
  17. Change From Baseline of Mean Actigraphy Sleep Efficiency (aSE) During Week 1 of Treatment [ Time Frame: Baseline, Week 1 ]
  18. Change From Baseline of Mean aSE During Week 2 of Treatment [ Time Frame: Baseline, Week 2 ]
  19. Change From Baseline of Mean aSE During Week 3 of Treatment [ Time Frame: Baseline, Week 3 ]
  20. Change From Baseline of Mean aSE During Week 4 of Treatment [ Time Frame: Baseline, Week 4 ]
  21. Change From Baseline of Mean Actigraphy Wake Efficiency (aWE) During Week 1 of Treatment [ Time Frame: Baseline, Week 1 ]
  22. Change From Baseline of Mean aWE During Week 2 of Treatment [ Time Frame: Baseline, Week 2 ]
  23. Change From Baseline of Mean aWE During Week 3 of Treatment [ Time Frame: Baseline, Week 3 ]
  24. Change From Baseline of Mean aWE During Week 4 of Treatment [ Time Frame: Baseline, Week 4 ]
  25. Change From Baseline in Intradaily Variability (IV) Over Week 1 of Treatment [ Time Frame: Baseline, Week 1 ]
  26. Change From Baseline in IV Over Week 2 of Treatment [ Time Frame: Baseline, Week 2 ]
  27. Change From Baseline in IV Over Week 3 of Treatment [ Time Frame: Baseline, Week 3 ]
  28. Change From Baseline in IV Over Week 4 of Treatment [ Time Frame: Baseline, Week 4 ]
  29. Change From Baseline in Interdaily Stability (IS) Over Week 1 of Treatment [ Time Frame: Baseline, Week 1 ]
  30. Change From Baseline in IS Over Week 2 of Treatment [ Time Frame: Baseline, Week 2 ]
  31. Change From Baseline in IS Over Week 3 of Treatment [ Time Frame: Baseline, Week 3 ]
  32. Change From Baseline in IS Over Week 4 of Treatment [ Time Frame: Baseline, Week 4 ]
  33. Change From Baseline in the Activity Across the Least Active 5-hour Period per 24-hour Period (L5) Over Week 1 of Treatment [ Time Frame: Baseline, Week 1 ]
  34. Change From Baseline in the Activity Across the Least Active 5-hour Period per 24-hour Period (L5) Over Week 2 of Treatment [ Time Frame: Baseline, Week 2 ]
  35. Change From Baseline in the Activity Across the Least Active 5-hour Period per 24-hour Period (L5) Over Week 3 of Treatment [ Time Frame: Baseline, Week 3 ]
  36. Change From Baseline in the Activity Across the Least Active 5-hour Period per 24-hour Period (L5) Over Week 4 of Treatment [ Time Frame: Baseline, Week 4 ]
  37. Change From Baseline in the Activity During the Most Active 10-hour Period per 24-hour Period (Mean M10) Over Week 1 of Treatment [ Time Frame: Baseline, Week 1 ]
  38. Change From Baseline in the Activity During the Most Active 10-hour Period per 24-hour Period (Mean M10) Over Week 2 of Treatment [ Time Frame: Baseline, Week 2 ]
  39. Change From Baseline in the Activity During the Most Active 10-hour Period per 24-hour Period (Mean M10) Over Week 3 of Treatment [ Time Frame: Baseline, Week 3 ]
  40. Change From Baseline in the Activity During the Most Active 10-hour Period per 24-hour Period (Mean M10) Over Week 4 of Treatment [ Time Frame: Baseline, Week 4 ]
  41. Change From Baseline in the Amplitude of the Rest-activity Rhythm Calculated as the Difference Between M10 and L5 (AMP) Over Week 1 of Treatment [ Time Frame: Baseline, Week 1 ]
  42. Change From Baseline in the Amplitude of the Rest-activity Rhythm Calculated as the Difference Between M10 and L5 (AMP) Over Week 2 of Treatment [ Time Frame: Baseline, Week 2 ]
  43. Change From Baseline in the Amplitude of the Rest-activity Rhythm Calculated as the Difference Between M10 and L5 (AMP) Over Week 3 of Treatment [ Time Frame: Baseline, Week 3 ]
  44. Change From Baseline in the Amplitude of the Rest-activity Rhythm Calculated as the Difference Between M10 and L5 (AMP) Over Week 4 of Treatment [ Time Frame: Baseline, Week 4 ]
  45. Change From Baseline in the Relative Amplitude of the Rest-activity Rhythm Calculated as the Difference Between M10 and L5 Divided by M10 Plus L5 (RA) Over Week 1 of Treatment [ Time Frame: Baseline, Week 1 ]
  46. Change From Baseline in the Relative Amplitude of the Rest-activity Rhythm Calculated as the Difference Between M10 and L5 Divided by M10 Plus L5 (RA) Over Week 2 of Treatment [ Time Frame: Baseline, Week 2 ]
  47. Change From Baseline in the Relative Amplitude of the Rest-activity Rhythm Calculated as the Difference Between M10 and L5 Divided by M10 Plus L5 (RA) Over Week 3 of Treatment [ Time Frame: Baseline, Week 3 ]
  48. Change From Baseline in the Relative Amplitude of the Rest-activity Rhythm Calculated as the Difference Between M10 and L5 Divided by M10 Plus L5 (RA) Over Week 4 of Treatment [ Time Frame: Baseline, Week 4 ]

Secondary Outcome Measures :
  1. Change From Baseline in the Neuropsychiatric Inventory (NPI-10) Total Score at Day 29 [ Time Frame: Baseline, Day 29 ]
  2. Change From Baseline in the Sleep Disorders Inventory (SDI) Score at Day 29 [ Time Frame: Baseline, Day 29 ]
  3. Number of Participants in Each Category of the Clinician's Global Impression of Change Irregular Sleep-Wake Rhythm Disorder (CGIC-ISWRD) Scale Overall Score at Day 29 [ Time Frame: Baseline, Day 29 ]
  4. Number of Participants With any Non-serious Adverse Event or any Serious Adverse Event [ Time Frame: Up to approximately 48 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 <87.5% within the defined nocturnal sleep period and mean 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

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 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
  • History of malignancy within the previous 5 years except for adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in situ
  • Any suicidal ideation with intent with or without a plan, at the time of or within 6 months of Screening, as indicated by answering "Yes" to questions 4 and 5 on the Suicidal Ideation section of the electronic version of the Columbia Suicide Severity Rating Scale (eC-SSRS)
  • Any suicidal behavior within the past 10 years based on the eC-SSRS
  • History of violence toward the caregiver or others
  • Scheduled for surgery using general anesthesia during the study
  • Used any prohibited prescription or over-the-counter concomitant medications within 1 week or 5 half-lives, whichever is longer, before starting actigraphy during Screening
  • Used any modality of treatment for ISWRD between Screening and Randomization based on approaches related to circadian rhythms, including phototherapy (light therapy), melatonin and melatonin agonists
  • Failed treatment with Belsomra (efficacy and/or safety) following treatment with an appropriate dose and of adequate duration in the opinion of the investigator
  • Transmeridian travel across more than 3 time zones between Screening and Randomization, or plans to travel across more than 3 time zones during the study
  • Hypersensitivity to lemborexant or to its excipients
  • Currently enrolled in another clinical trial, except for observational studies with no treatment component
  • Used any investigational drug or device before informed consent (ie, within 30 days or 5× the investigational drug half-life whichever is longer or 6 months for potential disease-modifying drugs)
  • Previously participated in any clinical trial of lemborexant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03001557


  Show 44 Study Locations
Sponsors and Collaborators
Eisai Inc.
Purdue Pharma LP

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Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT03001557     History of Changes
Other Study ID Numbers: E2006-G000-202
2017-003306-40 ( EudraCT Number )
First Posted: December 23, 2016    Key Record Dates
Last Update Posted: July 29, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Eisai Inc.:
Mild to Moderate Alzheimer's Disease Dementia
sleep
circadian rhythms

Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Disease
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders