A Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-42847922 in Participants With Insomnia Disorder

Change in LPS was measured on Night 1 by PSG. LPS is the time in minutes from 'lights out' that marks the starting of total recording time to the first epoch recorded as sleep. The LPS change from baseline on Night 1 was calculated as (LPS at Night 1 minus Baseline LPS). Negative changes in LPS indicated improvement.

PSG was used to measure the time to wake after initial sleep onset (WASO) over the first 6 hours on Night 1. Negative changes in WASO indicate improvement.

LPS was measured on Night 13 by PSG. LPS is the time in minutes from 'lights out' that marks the starting of total recording time to the first epoch recorded as sleep. Negative changes in LPS indicate improvement.

PSG was used to measure the time to wake after initial sleep onset (WASO) over the first 6 hours on Night 13. Negative changes in WASO indicate improvement.

TST is defined as the total sleep time in minutes. The total sleep time is the total amount of sleep time scored during the total recording time. Positive changes in TST indicate improvement.

TST is defined as the total sleep time in minutes. The total sleep time is the total amount of sleep time scored during the total recording time. Positive changes in TST indicate improvement.

Sleep efficiency was measured as the total sleep time divided by the total time in bed (that is, the number of hours from the beginning of the Polysomnography recording to the end of the recording) (in percentage). Positive changes in SE indicate improvement.

Polysomnography was used to measure the time to wake after initial sleep onset measured hourly on Day 1 and 13 from Hour 1 to Hour 8. WASO is measured during overnight sleep laboratory (PSG) assessment and defined as the duration of wakefulness from the onset of persistent sleep (that is, 10 consecutive minutes of sleep) over 8 hours of PSG assessment. Negative changes in WASO indicate improvement.

PSG was used to measure the number of night-time awakenings over the first 6 hours after initial sleep onset. Negative changes in nNAW indicate improvement.

PSG was used to measure wake time during the total recording period. Negative changes in wake during total sleep period indicate improvement.

PSG was used to measure the time awake after final awakening to the end of the PSG period. Negative changes in wake after final awakening indicate improvement.

PSG was used to measure number of night time awakenings per hour. Negative changes in nNAW/hr indicate improvement.

PSG was used to measure the time to first awakening after sleep onset. Positive changes in time to first awakening after sleep indicate improvement.

PSG was used to measure REM duration (time to first REM period from sleep onset).

PSG was used to measure the REM latency. REM latency was defined as the time to first REM from sleep onset to reaching the first epoch of REM sleep.

PSG was used to measure the sleep-onset REM in participants. REM sleep periods within 15 minutes from sleep onset were measured.

PSG was used to measure the number of sleep cycles.

PSG was used to measure total time spent in non-rapid eye movement sleep stages N1, N2 and N3. Total time spent was sum of N1, N2 and N3. Positive changes in NREM duration indicate improvement.

CSD-M is a standardized participant diary based on expert consensus and qualitative participant input to retrieve patient reported subjective sleep parameters related to prior night's sleep. CSD-M parameters analyzed includes: sSOL, sTST, sWASO. Negative change in sSOL, sWASO indicate improvement. Positive change in sTST indicates improvement.

The CSD-M is a standardized participant diary based on expert consensus and qualitative participant input to retrieve patient reported subjective sleep parameters related to the prior night's sleep. Sleep quality and how well rested participants felt at awaking are rated on a 5-point Likert scale ranging from 1 (very poor) to 5 (very good). Higher ratings indicate better sleep quality (sQUAL) and more refreshing/restorative quality of sleep (sFRESH). CSD-M parameters analyzed includes: sFRESH and sQUAL. Positive change in sFRESH and sQUAL indicates improvement.

CSD-M is a standardized participant diary based on expert consensus and qualitative participant input to retrieve patient reported subjective sleep parameters related to the prior night's sleep. CSD-M parameters analyzed include: s-nNAW. Negative change in s-nNAW indicate improvement.

PROMIS Sleep Disturbance (PROMIS-SD) Short Form subscale consists of a static 8-item questionnaire. Using a recall period of the past 7 days, it assesses the concepts of sleep initiation (2 items), quality of sleep (3 items), early morning feelings (2 items) and worrying about sleep (1 item). Each question has 5 response options ranging in value from 1 to 5. To find the total raw score for a short form with all questions answered, sum the values of the response to each question and a total score ranges from 8 to 40. Lower scores indicate less sleep disturbance. Negative changes in scores indicate improvement.

PROMIS-Sleep Related Impairment (PROMIS-SRI) scale consists of 8 items to evaluate daytime consequences of functioning 5-point Likert scale ranging from 1 to 5. PROMIS-SRI measures self-reported perceptions of alertness, sleepiness, and tiredness during usual waking hours, and perceived functional impairments during wakefulness associated with sleep problems or impaired alertness. Each question has five response options ranging in value from 1 to 5. To find total raw score (which range from 8 to 40) with all questions answered, sum values of response to each question. Higher score indicates greater sleep impairment.

The PGI-S is a self-reported scale to measure severity of illness using a 6-point scale ranging from 1 to 6, (1=no insomnia, 2=very mild, 3=mild, 4=moderate, 5=severe, 6=very severe). Considering all aspects of insomnia, participants rated their severity on the PGI-S scale. Negative changes in scores indicate improvement.

PGI-I is a self-reported scale to measure improvement in illness using a 7-point scale ranging from 1 to 7, (1=very much improved, 2=much improved, 3=improved [just enough to make a difference], 4=no change, 5=worse [just enough to make a difference], 6=much worse, 7=very much worse). Negative changes in scores indicate improvement.

Percentage of participants who achieved at least 50% reduction from baseline in ISI total score (responders) were reported. It is a 7-item questionnaire assessing nature, severity, impact of insomnia. Dimensions evaluated: severity of sleep onset, sleep maintenance, early morning awakening problems; sleep dissatisfaction; interference of sleep problem with daytime functioning; noticeability of sleep problems; distress caused by sleep difficulties. 5-point Likert scale (0-4) was used to rate each item, Scores are summed for a total score which ranges from 0-28. Negative changes in scores indicate improvement. ISI total score is the sum of all item scores. Total score interpreted insomnia as follows: absence (0-7); sub-threshold (8-14); moderate (15-21); severe (22-28).

Percentage of participants with remission of insomnia symptom defined as, total score of <= 10 on ISI scale. ISI is 7-item questionnaire assessing nature, severity, impact of insomnia. Dimensions evaluated are: severity of sleep onset, sleep maintenance, early morning awakening problems; sleep dissatisfaction; interference of sleep problem with daytime functioning; noticeability of sleep problems by others; distress caused by sleep difficulties. 5-point Likert scale (0-4) is used to rate each item. ISI total score is the sum of all item scores. ISI total score is the sum of all item scores. Scores are summed for a total score which ranges from 0-28 and interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); severe insomnia (22-28).

The CGI-S is a 7-point scale to measure severity of illness (1=normal [not at all ill], 2=borderline ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill participants). Higher score indicates more severity. Negative changes in scores indicate improvement.

The CGI-I is a 7-point scale to measure improvement in illness using a 7-point scale ranging from 1 to 7 (1=very much improved, 2=much improved, 3=minimally improved, 4=no change from baseline, 5=minimally worse, 6=much worse, 7=very much worse). Higher score indicates more severity. Negative changes in scores indicate improvement.

An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Treatment-emergent adverse events are adverse events with an onset date occurring at or after the initial administration of study drug through the Day 17 telephone contact date, or the day of last dose plus 3 days for participants without the Day 17 telephone contact date.

Treatment-emergent serious adverse events are serious adverse events with an onset date occurring at or after the initial administration of study drug through the Day 17 telephone contact date, or the day of last dose plus 3 days for participants without the Day 17 telephone contact date. Events of special interest included: Cataplexy; Sleep paralysis; Complex sleep-related behaviors such as confusional arousals, somnambulism (sleep walking), sleep terrors, bruxism (teeth grinding), sleep sex, sleep related eating disorder, sleep behavior disorder, and catathrenia (REM-associated end-inspiratory apnea/breath holding); Abnormal dreams; Falls.

Clinically significant vital signs (pulse, supine and standing blood pressure (systolic and diastolic), and oral, temperature) and physical abnormalities (body weight) were reported. Abnormally low parameters included pulse (bpm)- decrease value from baseline greater than or equal to (>=) 15 to <=50; Systolic BP (mmHg [Millimeter of mercury])- decrease value from baseline >=20 to <=90; Diastolic BP- decrease value from baseline >=15 to <=50; weight (Kilogram[Kg])- decrease from baseline >=7%; Body temperature (Celsius [C])- <35.5. Abnormally high parameters included pulse- increase value from baseline >=15 to >=100; Systolic BP(mmHg)- increase from baseline of >=20 to >=180; Diastolic BP- increase value from baseline >=15 to >=105; weight(Kg)- increase from baseline of >=7%; body temperature (C)- >37.5.

Twelve-lead ECGs were recorded in a supine position and different ECG intervals (Respiratory rate [RR], PR, time for ventricular depolarization [QRS], and total time from ventricular depolarization to complete repolarization [QT]) and heart rate was measured. This included heart rate:<=50 beats per minute (bpm) and >=100 bpm; PR interval <=120 millisecond (msec) and >=200 msec; QRS interval: <=60 msec and >=120 msec; QT interval:<=200 msec and >=500 msec.

Number of participants with clinically significant laboratory abnormalities were reported. Blood samples for serum chemistry (albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bicarbonate, calcium, chloride, creatine Kinase, gamma glutamyl transferase, lactate dehydrogenase, phosphate, potassium, sodium), and urinalysis (bilirubin, protein) were collected for clinical laboratory testing.

C-SSRS is a questionnaire designed to solicit occurrence, severity, frequency of suicidal ideation/behaviors using following scores: Suicidal Ideation-1:Wish to be Dead; 2:Non-specific Active Suicidal Thoughts; 3:Active Suicidal Ideation with Any Methods without Intent to Act; 4:Active Suicidal Ideation with Some Intent to Act; 5:Active Suicidal Ideation with Specific Plan/Intent; Suicidal Behavior-6:Preparatory Acts; 7:Aborted Attempt; 8:Interrupted Attempt; 9:Actual Attempt; 10:Completed Suicide. If no events qualify for score of 1-10, score 0 indicate "no event that can be assessed on basis of C-SSRS". Higher scores= greater severity.

The KSS is a patient reported assessment of level of drowsiness at the time of scale administration. This scale is focused mainly on the propensity to fall asleep and has a high validity in measuring sleepiness. It consists of a single item assessed on 9-point Likert scale with response options from: 1=very alert to 9=very sleepy (fighting sleep). Negative changes indicate improvement.

The body sway meter allows measurement of body movements in a single plane, providing a measure of postural stability. Body sway was measured using an ataxiameter. Participants were instructed to wear a pair of thin socks for each session. Before starting a measurement, participants were asked to stand still and comfortable, with their feet approximately 10 centimeters (cm) apart and their hands in a relaxed position alongside the body and eyes closed. The total period of body sway measurement was 2 minutes.

Power of Attention is a combination of the speed scores from the three tests of attention, and is established to reflect the ability to focus attention and to process information. Power of Attention was calculated from the sum of the reaction time measured from the attentional tasks (Simple Reaction Time, Choice Reaction Time and Digit Vigilance Speed). Score ranges from 450 milliseconds - 61500 milliseconds. A low score reflects a fast reaction time and a high intensity of concentration.

Continuity of attention is a measure of sustained attention, combining (summed) accuracy and error measures from the choice reaction time and digit vigilance tasks. The number of correct responses (out of 50) for choice reaction time was added to the total number of targets correctly identified (out of 45) digit vigilance minus the number of false alarms (total score of -45 to 95). A high score reflects someone able to keep his/her mind on a single task for a prolonged period. A negative change from baseline reflects impairment compared to baseline.

Quality of working memory is a combination of the scores from Spatial Working Memory and Numeric Working Memory tasks, and is established to reflect the ability to temporarily hold numeric and spatial information in memory. Sum of Spatial and Numeric Working Memory sensitivity indices (SI) (accuracy) was used to calculate the quality of working memory. The quality of working memory score was calculated from formulae that combined the accuracy scores for the original as well as the new (distractor) stimuli. The range for both the numeric working memory and spatial working memory tasks SI are -1 to 1. Smaller scores reflect poorer ability (poorer quality of working memory),larger scores reflect better ability (better quality of working memory). Total score is the sum of Spatial Working Memory and Numeric Working Memory (ranges from -2 to 2). Smaller scores reflect poorer ability (poorer quality of working memory), larger scores reflect better ability (better quality of working memory.

Quality of episodic secondary memory is calculated from the sum of 4 tests: Immediate and delayed word recall, and word and picture recognition, and ranges from -200 to 400. A high score reflects a good ability to store, hold and retrieve information of an episodic nature (that is an event or a name) and a negative change from baseline reflects impairment compared to baseline.

The sum of the speed measures from the two working memory tasks (Spatial and Numeric) and the two recognition tasks (Word and Picture). Speed of Memory combines reaction times from Spatial Working Memory (range:150 to 30000 millisecond [ms]), Numeric Working Memory (150 to 30000 ms), Word Recognition (250 to 30000 ms) and Picture recognition (250 to 30000 ms) tasks. The total reaction time (sum of above 4 reaction times) measures memory retrieval speed which ranges from 800 to 120000 ms. Slower reaction time reflect poorer ability and faster reaction time reflect better ability.

CSD-M is a standardized participant diary based on expert consensus and qualitative participant input to retrieve patient reported subjective sleep parameters related to prior night's sleep. Negative change in sSOL, sWASO indicate improvement and positive change in Subjective Total Sleep Time (sTST) indicates improvement.

CSD-M is a standardized subject diary based on expert consensus and qualitative subject input to retrieve patient reported subjective sleep parameters related to the prior night's sleep. Sleep quality (sQUAL) and how well rested subjects felt at awaking are rated on a 5-point Likert scale ranging from 1 (very poor) to 5 (very good). Higher ratings indicate better sleep quality and more refreshing/restorative quality of sleep (sFRESH). CSD-M parameters analyzed includes: sFRESH and sQUAL. Positive change in sFRESH and sQUAL indicates improvement.

CSD-M is a standardized participant diary based on expert consensus and qualitative participant input to retrieve patient reported subjective sleep parameters related to the prior night's sleep. Higher ratings indicate better sleep quality and more refreshing/restorative quality of sleep. CSD-M parameters analyzed includes: s-nNAW. Negative change in s-nNAW indicate improvement.

PWC-20 is a reliable, sensitive instrument having 20-items used to assess potential withdrawal symptoms following cessation of treatment. Items are as follows: Loss of Appetite, Nausea-Vomiting, Diarrhea, Anxiety-Nervousness, Irritability, Dysphoric Mood-Depression, Insomnia, Fatigue, Poor Coordination, Restlessness, Diaphoresis, Tremor, Dizziness, Headaches, Stiffness, Weakness, Increased Acuity Sound Smell Touch (IASST), Paresthesias, Remember, Derealization. Each item score ranges from 0 (not present)-3 (severe), where higher scores = more affected condition. Total score ranges from 0-60, where higher score indicates more affected condition. PWC-20 score was imputed as follows: sum of the non-missing items * (total number of items) / (number of items non-missing).

The BWSQ is a 20 symptom self-reported questionnaire to investigate withdrawal symptoms. Total score is the sum of item scores. Total scores can range from 0-40 with higher scores indicating greater severity of symptoms. Participants rated the degree to which they were experiencing each symptom as either "0=No," "1=Yes-moderate" or "2=Yes-severe". The questionnaire had been shown to be reliable and to have acceptable construct validity in assessing withdrawal symptoms.