Clinical trial NCT04009577: A Study to Evaluate Next-Dose Transition From Zolpidem to Lemborexant (LEM) for the Treatment of Insomnia
Official title: A Multicenter, Pilot Study to Evaluate Next-Dose Transition From Zolpidem to Lemborexant for the Treatment of Insomnia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Insomnia
Keywords: Insomnia
Sleep Initiation and Maintenance Disorders
Insomnia Disorder
Sleeplessness
E2006
Zolpidem
Lemborexant
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-05
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 transition to lemborexant 5 milligram (mg) (LEM5) or 10 mg (LEM10) after 2 weeks of receiving LEM.


Eligibility 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

Primary outcomes:
measure: Percentage of Overall Participants Who Transitioned to LEM at the End of the Titration Period of Core Study
timeFrame: Up to 2 Weeks
Secondary outcomes:
measure: Percentage of Participants Who Transitioned to LEM at the End of the 2-Week Titration Period of Core Study Within Each Cohort
timeFrame: Up to 2 Weeks
measure: Percentage of Participants in the LEM5 Treatment Groups With Dose Increasing to LEM10 at the End of the Titration Period of Core Study by Cohort and Overall
timeFrame: Up to 2 Weeks
measure: Percentage of Participants in LEM10 Treatment Group With Dose Decreasing to LEM5 at the End of the Titration Period of Core Study in Cohort 2
timeFrame: Up to 2 Weeks
measure: 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 of Core Study by Cohort and Overall Using End of the Titration Period Treatment
timeFrame: Up to 2 Weeks
Other outcomes:
Locations:
city: Glendale
country: United States
facility: PACT
state: Arizona
city: Sacramento
country: United States
facility: Northern California Research Corp
state: California
city: San Diego
country: United States
facility: Artemis Institute For Clinical Research LLC - San Diego - ClinEdge - PPDS
state: California
city: Santa Ana
country: United States
facility: SDS Clinical Trials, Inc.
state: California
city: Fleming Island
country: United States
facility: Fleming Island Center For Clinical Research - ERN-PPDS
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions Inc
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions Inc
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research Inc. - BTC - PPDS
state: Georgia
city: Stockbridge
country: United States
facility: SleepCare Research Institute Inc
state: Georgia
city: Chicago
country: United States
facility: Chicago Research Center Inc - ClinEdge - PPDS
state: Illinois
city: Elkridge
country: United States
facility: Centennial Medical Group - Elkridge - Rx Trials
state: Maryland
city: Albuquerque
country: United States
facility: Albuquerque Neurosciences Inc
state: New Mexico
city: New York
country: United States
facility: Clinilabs Drug Development Corporation
state: New York
city: Cincinnati
country: United States
facility: CTI Clinical Research Center - ClinEdge - PPDS
state: Ohio
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions Inc
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Trials of Neurology
state: Texas
Study officials:
References: