| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Sleeplessness (Sleep disorder where people have trouble sleeping) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10078083 |
| E.1.2 | Term | Insomnia disorder |
| E.1.2 | System Organ Class | 100000004873 |
|
| 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 |
1. To assess the dose-response of 3 doses of JNJ-42847922 (5, 10, and 20 mg) compared to placebo on an objective measure of sleep onset
in subjects with insomnia disorder. |
|
| E.2.2 | Secondary objectives of the trial |
1. To assess the dose-response of 3 doses of JNJ-42847922 (5, 10, and 20 mg) compared to placebo on an objective measure of maintenance of sleep in subjects with insomnia disorder.
2. To assess the effect of JNJ-42847922 compared with placebo in improving additional objective sleep parameters.
3. To assess the effect of JNJ-42847922 compared with zolpidem in improving objective sleep parameters.
4.To assess the effect of JNJ-42847922 compared with zolpidem and placebo on self-reported measures of sleep.
5. To assess the effect of JNJ-42847922 compared with zolpidem and placebo in improving: Response and remission of insomnia symptoms and clinical severity and improvement of insomnia symptoms.
6. To assess the safety and tolerability of JNJ-42847922 compared with zolpidem and placebo in subjects with insomnia disorder.
(Please refer to protocol for additional secondary objectives) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject must be a man or woman, 18 to 85 years of age, inclusive, on the day of signing informed consent. Note: Subjects should be at least 18 years of age or older as per the legal age of consent in the jurisdiction in which the study is taking place. For subjects ≥65 years of age, a Mini-Mental State Examination score of ≥25 to rule out cognitive impairment in the interest of subject safety.
2. Subject must meet DSM-5 criteria for insomnia disorder.
•A predominant complaint of dissatisfaction with sleep quantity or quality, associated with one (or more) of the following symptoms:
– Difficulty initiating sleep
– Difficulty maintaining sleep, characterized by frequent awakenings or problems returning to sleep after awakenings
– Early-morning awakening with inability to return to sleep.
•The sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning.
•The sleep difficulty occurs at least 3 nights per week.
•The sleep difficulty is present for at least 3 months.
•The sleep difficulty occurs despite adequate opportunity for sleep.
•The insomnia is not better explained by and does not occur exclusively during the course of another sleep-wake disorder (eg, narcolepsy, a breathing-related sleep disorder, a circadian rhythm sleep-wake disorder, a parasomnia).
•The insomnia is not attributable to the physiological effects of a substance (eg, a drug of abuse, a medication).
•Coexisting mental disorders and medical conditions do not adequately explain the predominant complaint of insomnia.
3. Subject must have an ISI total score ≥15 at screening.
(Note: For subjects taking hypnotic drugs at the time of signing the informed consent form [ICF], administration of the ISI must occur at least 5 days after the last dose of all hypnotic drugs.)
4. Subject must have an sSOL ≥45 minutes and an sWASO ≥60 minutes on at least 3 nights over any 7-day period during Part 1 of screening, using the CSD-M, prior to screening PSG assessments.(Note: For subjects taking hypnotic drugs at the time of signing the ICF, administration of the CSD-M must start at least 5 days after the last dose of all hypnotic drugs.)
5. Subject must demonstrate a 2-night mean LPS of ≥25 minutes (with neither night <20 minutes), a 2-night mean WASO ≥30 minutes, and a 2-night mean TST ≤6.5 hours, with neither night >7 hours.
6. Before randomization, a woman must be either: Not of childbearing potential defined as: postmenopausal OR permanently sterile. Or of childbearing potential and practicing a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) and agrees to remain on a highly effective method throughout the study and for at least 1 month after the last dose of study drug.
A woman using oral contraceptives must use an additional birth control method.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually active becomes active) a woman must begin a highly effective method of contraception, as described throughout the inclusion criteria. (NOTE additional requirements and definitions for this incision criteria can be found within the protocol).
(Please refer to protocol for additional inclusion criteria) |
|
| E.4 | Principal exclusion criteria |
1. Has history of or current clinically significant and/or unstable liver (moderate or severe hepatic impairment [Child-Pugh Score ≥7]) or renal insufficiency (severe renal impairment [estimated creatinine clearance below 30 mL/min]; serum creatinine >2 mg/dL); significant and/or unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, immunologic, or metabolic disturbances. Organic brain disease, epilepsy, dementia, and known or suspected mental retardation are exclusionary. Any clinically relevant medical condition that is likely to result in deterioration of the subject's condition or affect the subject's safety during the study (eg, medically frail subject with history of hospitalization due to fractures) or could potentially alter the absorption, metabolism, or excretion of the study drug is
exclusionary.
2. Has uncontrolled hypertension (supine systolic blood pressure >150 mm Hg in adult subjects or >160 mm Hg in elderly subjects or supine diastolic blood pressure >90 mm Hg, despite diet, exercise, or a stable dose of allowed antihypertensive therapy)
at screening or Day 1. (A subject with hypertension may be included if the subject’s hypertension has been controlled for at least 3 months prior to screening, and the dosage of any antihypertensive medication has been stable for the past 3 months).
3. Has clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening. Subjects with non-insulin dependent diabetes mellitus who are adequately controlled (hemoglobin A1c [HbA1c] ≤8%) may be eligible to participate if
otherwise medically healthy. It is expected that laboratory values will generally be within the normal range, though minor deviations, which are not considered to be of clinical significance to both the investigator and the sponsor’s Safety Physician, are acceptable.
4. Has clinically significant ECG abnormalities at screening or Day 1 prior to randomization defined as: QT interval corrected according to Fridericia’s formula: ≥450 msec (males); ≥470 msec (females). Evidence of 2nd and 3rd degree atrioventricular block, or 1st degree atrioventricular block with PR interval >200 msec, left bundle branch block. Features of new ischemia and other clinically important arrhythmia.
Note: Subjects with right bundle branch block may be allowed provided confirmation that right bundle branch block is not associated with underlying cardiac/lung diseases.
5. Has significant hypersomnia not related to night time insomnia (based on clinical judgment of the investigator).
6. Has a current or recent history of serious suicidal ideation within the past 6 months, corresponding to a positive response on item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan andintent) for ideation on the C-SSRS, or a history of suicidal behavior within the past year, as validated by the C-SSRS at screening or Day 1. Subjects with a prior suicide attempt of any sort, or prior serious suicidal ideation/plan within the past 6 months, should be carefully screened for current suicidal ideation and only subjects with non-serious items (1-3 of the suicidal ideation section of the C-SSRS) may be included at the discretion of the investigator.
7. Has insomnia related to RLS (defined as PLM-arousal index of ≥10 PLM-related electroencephalograph (EEG) arousals per hour of sleep for adult subjects or >15 for elderly subjects), sleep breathing disorder (defined as an apnea-hypopnea index ≥10 cumulative apneas and hypopneas per hour of EEG sleep for adult subjects or >15 for elderly subjects), or parasomnias. These disorders will be ruled out by the first PSG recording during Part 2 of screening.
(Please refer to protocol for additional exclusion criteria) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in latency to persistent sleep (LPS) as measured by polysomnography (PSG) on Night 1. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Polysomnography (PSG) during night of day 1 till morning of day 2. |
|
| E.5.2 | Secondary end point(s) |
1.Change from baseline in wake after sleep onset (WASO) over the first 6 hours as measured by PSG on Night 1.
2.Change from baseline in PSG parameters
including: LPS on Night 13, WASO over the first 6 hours on Night 13, Total sleep time (TST) (over 6 and 8 hours) on Nights 1 and 13, Sleep efficiency (SE) on Nights 1 and 13 and other secondary PSG sleep parameters (detailed in Section 9.2.1)on Nights 1 and 13
3. Patient-reported measures including: Change from baseline in subjective sleep parameters as measured by the Consensus Sleep Diary – Morning Administration (CSD-M), in the morning on Days 2 and 14. Change from baseline in sleep disturbance and impairment as measured by the National Institutes of Health Patient Reported Outcome Measurement Information System (PROMIS) short form 8a for Sleep Disturbance (PROMIS-SD) and PROMIS short form 8a for Sleep Related Impairment (PROMIS-SRI) on Days 8 and 14. Change from baseline in subject's assessment of insomnia severity using the Patient Global Impression – Severity (PGI-S) scale and
subject's assessment of improvement in insomnia using the Patient Global Impression – Improvement (PGI-I) scale on Day 14.
4. Proportion of responders, defined as a ≥50% reduction from baseline in total score on the Insomnia Severity Index (ISI) on Day 14. Proportion of subjects with remission of insomnia symptoms, defined as a total score ≤10 on the ISI on Day 14.
5. Change from baseline in clinician's assessment of insomnia severity using the Clinical Global Impression – Severity (CGI-S) and improvement in insomnia using the Clinical Global Impression – Improvement (CGI-I) on Day 14.
6. Safety assessments including: Adverse events (AEs), Proportion of all serious AEs (SAEs) and events of special interest (e.g., falls, parasomnias), Vital signs, physical examinations, electrocardiogram (ECG), laboratory parameters and Columbia Suicide Severity Rating Scale (C-SSRS).
Residual effects as measured by: The presence of next day subjective residual effects as measured by the Karolinska Sleepiness Scale (KSS) on Days 2 and 14. Postural stability (body sway) as measured with an ataxiameter on Days 2 and 14 in the morning and on Day 15 at 4-hours post night 14 dose (middle of the night awakening).
(Please refer to protocol for additional secondary endpoints) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Time point(s) stated above in E.5.2 |
|
| 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 | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | 5 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| 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 |
| Belgium |
| France |
| Germany |
| Japan |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
|
| 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 | 6 |
| 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 | 6 |
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