E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment for insomnia disorder |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behaviours [F01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Demonstrate using polysomnography (PSG) that lemborexant (LEM10 and LEM5) is superior to placebo (PBO) on objective sleep onset as assessed by latency to persistent to sleep (LPS) after the last 2 nights of 1 month of treatment in subjects 55 years and older with insomnia disorder |
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E.2.2 | Secondary objectives of the trial |
Demonstrate that lemborexant (LEM10 and LEM5) is superior to PBO on sleep maintenance as assessed by SE after the last 2 nights of treatment
Demonstrate that lemborexant (LEM10 and LEM5) is superior to PBO on wake after sleep onset (WASO) after the first 2 nights of treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male age 65 years or older or female, age 55 years or older at the time of informed consent
2. Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for Insomnia Disorder, as follows:
o 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 (Note that if the complaint is limited to difficulty initiating
sleep, the subject is not eligible)
o Frequency of complaint ≥ 3 times per week
o Duration of complaint ≥ 3 months
o Associated with complaint of daytime impairment
3. At Screening: History of subjective WASO (sWASO) typically ≥ 60 minutes on at least 3 nights per week in the previous 4 weeks
4. At Screening: Reports regular time spent in bed, either sleeping or trying to sleep, between 7 and 9 hours
5. At Screening: Reports habitual bedtime, defined as the time the subject attempts to sleep, between 21:00 and 24:00 and habitual waketime between 05:00 and 09:00
6. At Screening and at check-in before the first PSG during the Run-in Period: ISI score ≥13 (revised per Amendment 02)
7. Confirmation of current insomnia symptoms as determined from responses on the Sleep Diary on the 7 most recent mornings (minimum 5 of 7 for eligibility) before the second screening visit, such that sWASO ≥ 60 minutes on at least 3 of the 7 nights
8. Confirmation of regular bedtime and waketime as determined from responses on the Sleep Diary on the 7 most recent mornings before the second screening visit, such that neither bedtime, (defined as the time the subject attempts to try to sleep), nor waketime (defined as the time the subject gets out of bed for the day) deviates more than 1 hour on more than 2 nights from the calculated MHB or median habitual waketime, respectively, from the Screening Sleep Diary entries
9. Confirmation of sufficient duration of time spent in bed, as determined from responses on the Sleep Diary on the 7 most recent mornings before the second screening visit, such that there is not more than 2 nights with time spent in bed duration < 7 hours or > 10 hours (revised per Amendment 02)
10. During the Run-in Period: Reconfirmation of insomnia symptoms, as determined from responses on the Sleep Diary on the 7 most recent mornings before the first PSG during the Run-in Period, such that sWASO ≥ 60 minutes on at least 3 of the 7 nights
11. During the Run-in Period: Reconfirmation of regular bedtimes and waketimes as defined in Inclusion Criterion 8
12. During the Run-in Period: Reconfirmation of sufficient duration of time spent in bed as defined in Inclusion Criterion 9 (revised per Amendment 02)
13. During the Run-in Period: Objective (PSG) evidence of insomnia as follows:
WASO average ≥ 60 minutes on the 2 consecutive PSGs, with neither
night < 45 minutes (revised per Amendment 02)
14. Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night
15. Willing not to start a behavioral or other treatment program for the treatment of insomnia during the subject’s participation in the study |
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E.4 | Principal exclusion criteria |
1. A current diagnosis of sleep-related breathing disorder (including obstructive sleep apnea with or without continuous positive airway pressure [CPAP] treatment), periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or narcolepsy, or an exclusionary score on screening instruments to rule out individuals with symptoms of certain sleep disorders other than insomnia as follows: (revised per Amendment 01)
a. STOPBang score ≥5
b. International Restless Legs Scale score ≥16
c. Epworth Sleepiness Scale score >15 (Scores of 11-15 require excessive daytime sleepiness to be recorded in subject's Medical History) (revised per Amendments 01 and 02)
2. 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 (revised per Amendment 01)
3. On the MUPS, endorsed the item that corresponds to a history of sleep-eating or reports a history of sleep-related violent behaviour, sleep-driving or symptoms of another parasomnia that in the investigator's opinion make the subject unsuitable for the study (revised per Amendment 02)
4. Apnea-Hypopnea Index > 15 or Periodic Limb Movement with Arousal Index > 15 as measured on the PSG at the second screening visit
5. Beck Depression Inventory – II (BDI-II) score >19 at Screening
6. Beck Anxiety Inventory (BAI) score >15 at Screening
7. Habitually naps during the day more than 3 times per week
8. Is a female of childbearing potential
Note: All females will be considered to be of childbearing potential unless they are postmenopausal (defined as amenorrheic for at least 12 consecutive months, are in the appropriate age group, and are postmenopausal 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)
9. Excessive caffeine use that in the opinion of the investigator contributes to the subject’s insomnia, or habitually consumes caffeine-containing beverages after 18:00 and is unwilling to forego caffeine after 18:00 for the duration of his/her participation in the study
15. Current evidence of clinically significant disease (eg, cardiac; respiratory including chronic obstructive pulmonary disease, acute and/or severe respiratory depression; gastrointestinal including severe hepatic impairment; renal including severe renal impairment; neurological including myasthenia gravis; psychiatric disease; malignancy within the past 5 years other than adequately treated basal cell carcinoma) or chronic pain that in the opinion of the investigator(s) could affect the subject’s safety or interfere with the study assessments, including the ability to perform tasks on the cognitive PAB. Subjects for whom a sedating drug would be contraindicated for safety reasons because of the subject’s occupation or activities are also excluded. (revised per Amendment 01)
16. Comorbid nocturia resulting in frequent need to get out of bed to use the bathroom during the night
17. Any history of a medical or psychiatric condition that in the opinion of the investigator(s) could affect the subject’s safety or interfere with the study assessments, including the ability to perform the PAB
18. Any suicidal ideation with intent with or without a plan, at the time of or within 6 months before the eC-SSRS administration during the Prerandomization Phase (ie, answering “Yes” to questions 4 or 5 on the Suicidal Ideation section of the eC-SSRS)
20. Scheduled for surgery during the study
21. 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 (Run-in Period). (revised per Amendment 01)
22. Used any modality of treatment for insomnia, including cognitive behavioral therapy or marijuana within 1 week or 5 half-lives, whichever is longer, before the first dose of study medication (Run-in Period) (revised per Amendment 01)Failed treatment with suvorexant (Belsomra®) (efficacy and/or safety) following treatment with an appropriate dose and of adequate duration in the opinion of the investigator |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline of mean LPS on Days 29 and 30 of LEM10 and LEM5 compared to PBO |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change from baseline of mean SE on Days 29 and 30 of LEM10 and LEM5 compared to PBO
Change from baseline of mean WASO on Days 29 and 30 of LEM10 and LEM5 compared to PBO |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Germany |
Italy |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 19 |