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A Study to Evaluate Next-Dose Transition From Zolpidem to Lemborexant (LEM) for the Treatment of Insomnia

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ClinicalTrials.gov Identifier: NCT04009577
Recruitment Status : Recruiting
First Posted : July 4, 2019
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Brief Summary:
The primary objective of the study is to evaluate the proportion of adult [greater than or equal to (>=) 18 years] participants with insomnia disorder taking zolpidem tartrate immediate release (ZOL-IR) or zolpidem tartrate extended release (ZOL-ER), intermittently or frequently, who successfully transition to lemborexant 5 milligram (mg) (LEM5) or 10 mg (LEM10) after 2 weeks of receiving LEM.

Condition or disease Intervention/treatment Phase
Insomnia Drug: LEM 5 mg Drug: LEM 10 mg Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Pilot Study to Evaluate Next-Dose Transition From Zolpidem to Lemborexant for the Treatment of Insomnia
Actual Study Start Date : July 15, 2019
Estimated Primary Completion Date : December 13, 2019
Estimated Study Completion Date : April 2, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1 (LEM 5 mg)
Participants who were taking zolpidem tartrate (ZOL) at least 3 but fewer than 5 nights per week, for each of at least 2 weeks of the 3-week Screening Period, will initially receive LEM 5 mg administered as a tablet, orally for up to 2 weeks.
Drug: LEM 5 mg
LEM tablet.
Other Name: E2006

Experimental: Cohort 2A (LEM 5 mg)
Participants who were taking ZOL at least 5 nights per week, during, at minimum, the last 2 weeks of the 3-week Screening Period, will initially receive LEM 5 mg administered as a tablet, orally for up to 2 weeks.
Drug: LEM 5 mg
LEM tablet.
Other Name: E2006

Experimental: Cohort 2B (LEM 10 mg)
Participants who were taking ZOL at least 5 nights per week, during, at minimum, the last 2 weeks of the 3-week Screening Period, will initially receive LEM 10 mg administered as a tablet, orally for up to 2 weeks.
Drug: LEM 10 mg
LEM tablet.
Other Name: E2006




Primary Outcome Measures :
  1. Percentage of Overall Participants who Transition to LEM at the end of the Titration Period [ Time Frame: Up to 2 Weeks ]
    Transition to LEM is defined as a participant who remains on LEM at the end of the 2-week titration period and either 1) enters the extension phase, or 2) chooses to not enter the extension phase for reasons not related to LEM (including, but not limited to, time commitment related to the study, study-related travel expenses or preference to continue insomnia management with another health care provider).


Secondary Outcome Measures :
  1. Percentage of Participants who Transition to LEM at the end of the 2-Week Titration Period Within Each Cohort [ Time Frame: Up to 2 Weeks ]
  2. Percentage of Participants With Positive Medication Effect Rating on Each Patient Global Impression of Insomnia (PGI-I) Item at the end of the 2-Week Titration Period by Cohort and Overall Using End of the Titration Period Treatment [ Time Frame: Up to 2 Weeks ]
    The PGI-I is a self-report assessment of participant perception of the effects of a medication on their sleep. The PGI-I has 3 items related to study medication effects (a) helped/worsened sleep, (b) decreased/increased time to fall asleep, (c) increased/decreased total sleep time, and 1 item related to perceived appropriateness of study medication strength. The first 3 items are answered on a 3-point scale (1=positive medication effect, 2=neutral medication effect, 3=negative medication effect) and the last item on a different 3 point scale (medication: 1=too strong, 2=just right, 3=too weak). The PGI-I will be completed each morning following a dose of ZOL or LEM taken the prior evening during the screening and titration periods.

  3. Change From Baseline in Mean Insomnia Severity Index (ISI) Score at the end of the Titration Period by Cohort and Overall Using end of the Titration Period Treatment [ Time Frame: Up to 2 Weeks ]
    The ISI is a 7-item self-report questionnaire assessing the nature, severity and impact of insomnia. The dimensions evaluated are severity of: sleep onset, sleep maintenance, early-morning awakening problems; sleep dissatisfaction; interference of sleep difficulties with daytime functioning, noticeability of the sleep problems by others, and distress caused by the sleep difficulties. A 5-point likert scale is used to rate each item (from 0=no problem, to 4=very severe problem), yielding a total score from 0 to 28. Higher score indicate worse severity.

  4. Percentage of Participants in the LEM5 Treatment Groups With Dose Increasing to LEM10 at the end of the Titration Period by Cohort and Overall [ Time Frame: Up to 2 Weeks ]
  5. Percentage of Participants in LEM10 Treatment Group With Dose Decreasing to LEM5 at the end of the Titration Period in Cohort 2 [ Time Frame: Up to 2 Weeks ]
  6. Change From Baseline in Mean Quality of Sleep Rating Score by Cohort and Overall Using end of the Titration Period Treatment [ Time Frame: Up to 2 Weeks ]
    The quality of sleep rating is a self-reported scale in which participants are asked, "How would you rate the quality of your sleep last night, with 1 being extremely poor, 5 being not good or poor, and 9 being extremely good?" For quality of sleep, higher values are better. The quality of sleep rating will be completed each morning following a dose of ZOL or LEM taken the prior evening during the screening and titration periods.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Meets the Diagnostic and Statistical Manual of Mental Disorders, 5th ed (DSM-5) criteria for Insomnia Disorder, either currently or prior to zolpidem use, as follows:

    • Complains of dissatisfaction with nighttime sleep, in the form of difficulty staying asleep and/or awakening earlier in the morning than desired despite adequate opportunity for sleep
    • Frequency of complaint >=3 times per week
    • Duration of complaint >=3 months
    • Associated with complaint of daytime impairment
  2. Reports spending at least 7 hours in bed per night
  3. History of intermittent [taking zolpidem at least 3 or 4 nights per week], or frequent use (at least 5 nights per week) of ZOL-IR or ZOL-ER, for at least 1 month
  4. Confirmation of intermittent or frequent use of zolpidem (based on review of drug use data). Intermittent use is defined as taking zolpidem at least 3 but fewer than 5 nights per week, for at least 2 weeks each of the 3-week Screening Period. Frequent use is defined as taking zolpidem at least 5 nights per week, during, at minimum, the last 2 weeks of the 3-week Screening Period
  5. Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night
  6. Willing not to start another pharmacologic treatment for the management of insomnia during the participant's participation in the study

Exclusion Criteria:

  1. Females who are breastfeeding or pregnant at screening or baseline (as documented by a positive serum pregnancy test). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug
  2. Females of childbearing potential who:

    Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:

    • total abstinence (if it is their preferred and usual lifestyle)
    • an intrauterine device or intrauterine hormone-releasing system (IUS)
    • a contraceptive implant
    • an oral contraceptive (Participant must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 28 days after study drug discontinuation)
    • have a vasectomized partner with confirmed azoospermia
    • Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
  3. Any history of moderate or severe obstructive sleep apnea (OSA)
  4. Current evidence of a clinically significant, active respiratory disorder other than mild OSA. This includes bronchiectasis, emphysema, asthma, chronic obstructive pulmonary disease or any other pulmonary disorder identified by review of medical history or physical examination, and which in the opinion of the investigator, could compromise the participant's safety or interfere with study assessments
  5. A current diagnosis of periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or an exclusionary score on screening instruments to rule out individuals with symptoms of certain sleep disorders other than insomnia as follows:

    • STOP-Bang score >=5 (participants previously diagnosed with mild OSA are not excluded)
    • International Restless Legs Scale (IRLS) score >=16
  6. Habitually naps during the day more than 3 times per week
  7. Reports symptoms potentially related to narcolepsy, that in the clinical opinion of the investigator indicates the need for referral for a diagnostic evaluation for the presence of narcolepsy
  8. Reports a history of sleep-related violent behavior, or sleep driving, or any other complex sleep-related behavior (eg, making phone calls or preparing and eating food while sleeping), whether spontaneous or associated with a pharmacological sleep agent
  9. Takes a dose of ZOL-IR greater (>)10 mg per night, or ZOL-ER >12.5 mg per night
  10. Takes a dose of zolpidem that is lower than what is prescribed
  11. Reports having altered zolpidem tablets
  12. Unwilling to forgo alcohol consumption within 3 hours of bedtime for the duration of participation in the study
  13. Used any prohibited prescription or over-the-counter concomitant medications within 1-week or 5 half-lives, whichever is longer, before the first dose of study medication (A list of prohibited concomitant medications is presented in the protocol)
  14. Used any pharmacologic modality of treatment for insomnia other than zolpidem, including marijuana, within 1-week or 5 half-lives, whichever is longer, before the Screening Period
  15. A prolonged difference between QTc corrected by Fridericia's formulas (QTcF) interval [QTcF >450 millisecond (ms)] as demonstrated by a repeated electrocardiogram
  16. Any suicidal ideation with intent with or without a plan at Screening or within 6 months of Screening (ie, answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale [C-SSRS])
  17. Any lifetime suicidal behavior (per the Suicidal Behavior section of the C-SSRS)
  18. Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, and renal disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments. Participants for whom a sedating drug would be contraindicated for safety reasons because of the participant's occupation or activities are also excluded
  19. Hypersensitivity to LEM or any of the excipients
  20. Any history of or concomitant medical condition that in the opinion of the investigator(s) would compromise the participant's ability to safely complete the study
  21. Planned surgery that requires general, spinal, or epidural anesthesia that would take place during the study. Planned surgery, which requires only local anesthesia and which can be undertaken as a day case without inpatient stay postoperatively, need not result in exclusion if in the opinion of the investigator this operation does not interfere with the study procedures and patient safety
  22. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years
  23. History of drug or alcohol dependency or abuse within approximately the last 2 years
  24. Currently enrolled in another clinical study or used any investigational drug or device within 28 days or 5 times the half-life, whichever is longer, preceding informed consent
  25. Previously participated in any clinical trial of LEM

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): NCT04009577


Contacts
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Contact: Eisai Medical Information +1-888-274-2378 esi_medinfo@eisai.com

Locations
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United States, Arizona
PACT Not yet recruiting
Glendale, Arizona, United States, 85306
United States, California
Northern California Research Corp Not yet recruiting
Sacramento, California, United States, 95821
Artemis Institute For Clinical Research LLC - San Diego - ClinEdge - PPDS Recruiting
San Diego, California, United States, 92103
SDS Clinical Trials, Inc. Not yet recruiting
Santa Ana, California, United States, 92705
United States, Florida
Fleming Island Center For Clinical Research - ERN-PPDS Recruiting
Fleming Island, Florida, United States, 32003
MD Clinical Not yet recruiting
Hallandale Beach, Florida, United States, 33009
Clinical Neuroscience Solutions Inc Not yet recruiting
Jacksonville, Florida, United States, 32256
Clinical Neuroscience Solutions Inc Recruiting
Orlando, Florida, United States, 32801
United States, Georgia
NeuroTrials Research Inc. - BTC - PPDS Not yet recruiting
Atlanta, Georgia, United States, 30342
SleepCare Research Institute Inc Recruiting
Stockbridge, Georgia, United States, 30281
United States, Illinois
Chicago Research Center Inc - ClinEdge - PPDS Not yet recruiting
Chicago, Illinois, United States, 60634
United States, New Mexico
Albuquerque Neurosciences Inc Not yet recruiting
Albuquerque, New Mexico, United States, 87109
United States, New York
Clinilabs Drug Development Corporation Not yet recruiting
New York, New York, United States, 10019
United States, Ohio
CTI Clinical Research Center - ClinEdge - PPDS Not yet recruiting
Cincinnati, Ohio, United States, 45212
United States, Texas
FutureSearch Trials of Neurology Not yet recruiting
Austin, Texas, United States, 78731
Sponsors and Collaborators
Eisai Inc.

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Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT04009577     History of Changes
Other Study ID Numbers: E2006-A001-312
First Posted: July 4, 2019    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website https://eisaiclinicaltrials.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eisai Inc.:
Insomnia
Sleep Initiation and Maintenance Disorders
Insomnia Disorder
Sleeplessness
E2006
Zolpidem
Lemborexant
Additional relevant MeSH terms:
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Zolpidem
Sleep Initiation and Maintenance Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Mental Disorders
Sleep Aids, Pharmaceutical
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
GABA-A Receptor Agonists
GABA Agonists
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action