Clinical trial NCT03375203: A Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-42847922 in Participants With Insomnia Disorder
Official title: A Multicenter, Double-Blind, Randomized, Parallel-Group, Active- and Placebo-Controlled Polysomnography Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-42847922 in Subjects With Insomnia Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Insomnia Disorders
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-12-15
Enrollment: 365
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this 2 month phase 2b study is to investigate the dose response of 3 doses of JNJ-42847922 (Seltorexant) (5,10 and 20 mg) compared to placebo and zolpidem on sleep onset and maintenance and to further document safety and tolerability of JNJ-42847922 (Seltorexant) upon multiple (14 days) dose administration in participants with insomnia disorder.


Eligibility criteria: Inclusion Criteria:

* Participant must be a man or women of non-childbearing potential (WONCBP), 18 to 85 years of age, inclusive, on the day of signing informed consent. A WONCBP is defined as: a).Postmenopausal: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. b). Permanently sterile: Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy. c). If reproductive status is questionable, additional evaluation should be considered
* Participant must meet Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) criteria for insomnia disorder
* Participant must have an Insomnia Severity Index (ISI) total score greater than or equal to (\>=) 15 at screening
* Participant must have an self-reported sleep onset latency (sSOL) \>=45 minutes and a subjective wake after sleep onset (sWASO) \>= 60 minutes on at least 3 nights over any 7-day period during Part 1 of screening, using the Consensus Sleep Diary - Morning Administration (CSD-M), prior to screening polysomnography (PSG) assessments
* Participant must demonstrate a 2-night mean latency to persistent sleep (LPS) of \>= 25 minutes (with neither night less than \[\<\] 20 minutes), a 2 night mean wake after sleep onset (WASO) \>= 30 minutes, and a 2 night mean total sleep time (TST) less than or equal to (=\<) 6.5 hours, with neither night greater than (\>) 7 hours
* Participant must be otherwise healthy or present with stable, well-controlled, chronic conditions on the basis of physical examination, medical history, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests performed at screening

Exclusion Criteria:

* 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 \[estimated creatinine clearance below 30 {milliliter per minute} mL/min\]; serum creatinine \>2 \[milligram per deciliter\] mg/dL); significant and/or unstable cardiac, vascular, pulmonary (example, acute or severe respiratory failure), gastrointestinal, endocrine, neurologic (example, myasthenia gravis, narcolepsy), hematologic, rheumatologic, immunologic, or metabolic disturbances. Organic brain disease, epilepsy, dementia, narcolepsy, narrow angle glaucoma and known or suspected mental retardation are exclusionary. Any clinically relevant medical condition that is likely to result in deterioration of the participant's condition or affect the participant's safety during the study (eg, medically frail participant with history of hospitalization due to fractures) or could potentially alter the absorption, metabolism, or excretion of the study drug is exclusionary
* Has uncontrolled hypertension (supine systolic blood pressure \>150 millimeter of mercury (mm Hg) in adult participants or \>160 mm Hg in elderly participants 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 participant with hypertension may be included if the participant'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)
* Has clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening. Participants with non-insulin dependent diabetes mellitus who are adequately controlled (hemoglobin A1c \[HbA1c\] =\< 8 percent \[%\]) 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
* Has clinically significant ECG abnormalities at screening or Day 1 prior to randomization defined as:

  1. QT interval corrected according to Fridericia's formula: \>= 450 millisecond (msec) (males); \>= 470 msec (females).
  2. Evidence of 2nd and 3rd degree atrioventricular block, or 1st degree atrioventricular block with PR interval \>210 msec, left bundle branch block.
  3. Features of new ischemia.
  4. Other clinically important arrhythmia
* Has significant hypersomnia not related to night time insomnia (based on clinical judgment of the investigator)
* Regularly naps more than 3 times per week
* Has a current diagnosis or recent history of psychotic disorder, major depressive disorder (MDD), bipolar disorder, or posttraumatic stress disorder, or other psychiatric condition that, in the investigator's opinion, would interfere with the participant's ability to participate in the trial
* 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 and intent) for ideation on the Columbia Suicide Severity Rating Scale (C-SSRS), or a history of suicidal behavior within the past year, as validated by the C-SSRS at screening or Day 1. Participants 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 participants with non-serious items (1-3 of the suicidal ideation section of the C-SSRS) may be included at the discretion of the investigator
* Has insomnia related to restless leg syndrome (RLS) (defined as periodic leg movement \[PLM\]-arousal index of \>=10 PLM-related electroencephalograph (EEG) arousals per hour of sleep for adult participants or \>15 for elderly participants), sleep breathing disorder (defined as an apnea hypopnea index \>=10 cumulative apneas and hypopneas per hour of EEG sleep for adult participants or \>15 for elderly participants), or parasomnias. These disorders will be ruled out by the first PSG recording during Part 2 of screening
* Has known allergies, hypersensitivity, intolerance, lack of response, or any contraindication to JNJ-42847922 or zolpidem or their excipients
* Plans to father a child while enrolled in this study or within 3 months after the last dose of study drug; and/or, Is pregnant, or breastfeeding, while enrolled in this study or within 1 month after the last dose of study drug

Primary outcomes:
measure: Change From Baseline in Latency to Persistent Sleep (LPS) as Measured by Polysomnography (PSG) on Night 1
timeFrame: Baseline and Night 1
Secondary outcomes:
measure: Change From Baseline in Wake After Sleep Onset (WASO) Over the First 6 Hours as Measured by PSG on Night 1
timeFrame: Baseline and over first 6 hours on Night 1
measure: Change From Baseline in LPS as Measured by PSG on Night 13
timeFrame: Baseline and Night 13
measure: Change From Baseline in WASO Over the First 6 Hours as Measured by PSG on Night 13
timeFrame: Baseline and over first 6 hours on Night 13
measure: Change From Baseline in Total Sleep Time (TST) as Measured by PSG Over 6 Hours on Nights 1 and 13
timeFrame: Baseline, Over 6 hours on Nights 1 and 13
measure: Change From Baseline in Total Sleep Time (TST) as Measured by PSG Over 8 Hours on Nights 1 and 13
timeFrame: Baseline, Over 8 hours on Nights 1 and 13
measure: Change From Baseline in Sleep Efficiency (SE) Measured by PSG on Nights 1 and 13
timeFrame: Baseline, Nights 1 and 13
measure: Change From Baseline in Wake After Sleep Onset (WASO) Measured Hourly on Days 1 and 13 From Hour 1 to Hour 8
timeFrame: Baseline, Days 1 and 13 (Hours 1 to 8)
measure: Change From Baseline in Number of Night-time Awakenings (nNAW) Over 6 Hours on Day 1 and 13
timeFrame: Baseline, Over 6 hours on Day 1 and 13
measure: Change From Baseline in Wake During Total Sleep Period on Day 1 and 13
timeFrame: Baseline, Day 1 and 13
measure: Change From Baseline in Wake After Final Awakening on Day 1 and 13
timeFrame: Baseline, Day 1 and 13
measure: Change From Baseline in Number of Night-time Awakenings Per Hour (nNAW/hr) on Day 1 and 13
timeFrame: Baseline, Day 1 and 13
measure: Change From Baseline in Time to First Awakening After Sleep on Day 1 and 13
timeFrame: Baseline, Day 1 and 13
measure: Change From Baseline in Rapid Eye Movement (REM) Duration on Day 1 and 13
timeFrame: Baseline, Day 1 and 13
measure: Change From Baseline in Rapid Eye Movement (REM) Latency on Day 1 and 13
timeFrame: Baseline, Day 1 and 13
measure: Percentage of Participants With Sleep-Onset Rapid Eye Movement on Day 1 and 13
timeFrame: Day 1 and 13
measure: Change From Baseline in Number of Sleep Cycles on Day 1 and 13
timeFrame: Baseline, Day 1 and 13
measure: Change From Baseline in Total Time Spent in Non-Rapid Eye Movement Sleep on Day 1 and 13
timeFrame: Baseline, Day 1 and 13
measure: Change From Baseline in Subjective Sleep Parameters Using Consensus Sleep Diary - Morning Administration (CSD-M) on Days 2 and 14: Self-Reported Sleep-Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO), Subjective Total Sleep Time (sTST)
timeFrame: Baseline, Days 2 and 14
measure: Change From Baseline in Subjective Sleep Parameters Using Consensus Sleep Diary - Morning Administration (CSD-M) on Days 2 and 14: Subjective Refreshed Feeling on Waking (sFRESH) and Subjective Quality of Sleep (sQUAL)
timeFrame: Baseline, Days 2 and 14
measure: Change From Baseline in Subjective Sleep Parameters Using Consensus Sleep Diary - Morning Administration (CSD-M) on Days 2 and 14: Number of Nighttime Awakenings (s-nNAW)
timeFrame: Baseline, Days 2 and 14
measure: Change From Baseline in Sleep Disturbance as Measured by Patient Reported Outcome Measurement Information System - Sleep Disturbance (PROMIS-SD) Total Score on Days 8 and 14
timeFrame: Baseline, Days 8 and 14
measure: Change From Baseline in Impairment as Measured by Patient Reported Outcome Measurement Information System - Sleep Related Impairment (PROMIS-SRI) Total Score on Days 8 and 14
timeFrame: Baseline, Days 8 and 14
measure: Change From Baseline in Participant's Assessment of Insomnia Severity Using the Patient Global Impression - Severity (PGI-S) Scale Score on Day 14
timeFrame: Baseline and Day 14
measure: Participant's Assessment of Improvement in Insomnia Using the Patient Global Impression - Improvement (PGI-I) Scale Score on Day 14
timeFrame: Baseline and Day 14
measure: Percentage of Participants Who Achieved Response Based on Insomnia Severity Index (ISI) Total Score on Day 14 - Observed Case
timeFrame: Day 14
measure: Percentage of Participants Who Achieved Remission Based on Insomnia Severity Index (ISI) Total Score on Day 14 - Observed Case
timeFrame: Day 14
measure: Change From Baseline in Clinician's Assessment of Insomnia Severity Using the Clinical Global Impression - Severity (CGI-S) Score on Day 14
timeFrame: Baseline and Day 14
measure: Change From Baseline in Clinician's Assessment of Insomnia Improvement Using Clinical Global Impression-Improvement (CGI-I) Score on Day 14
timeFrame: Baseline and Day 14
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability
timeFrame: Up to Day 17
measure: Number of Participants With Treatment-Emergent Serious Adverse Events and Events of Special Interest
timeFrame: Up to Day 17
measure: Number of Participants With Clinically Significant Vital Signs and Physical Abnormalities
timeFrame: Up to Day 15
measure: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
timeFrame: Up to Day 14
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Up to Day 15
measure: Number of Participants With Suicidal Ideation and Behavior as Determined by Columbia Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Day 14
measure: Change From Baseline in Karolinska Sleepiness Scale (KSS) Total Score on Days 2 and 14
timeFrame: Baseline, Days 2 and 14
measure: Postural Stability Measured by Ataxiameter
timeFrame: Day 14 (morning)
measure: Change From Baseline in Power of Attention as Measured by a Computerized Battery of Cognitive Tests on Day 14 (Morning)
timeFrame: Baseline and Day 14 (Morning)
measure: Change From Baseline in Continuity of Attention as Measured by a Computerized Battery of Cognitive Tests on Day 14 (Morning)
timeFrame: Baseline and Day 14 (Morning)
measure: Change From Baseline in Quality of Working Memory as Measured by a Computerized Battery of Cognitive Tests on Day 14 (Morning)
timeFrame: Baseline and Day 14 (Morning)
measure: Change From Baseline in Quality of Episodic Secondary Memory as Measured by a Computerized Battery of Cognitive Tests on Day 14 (Morning)
timeFrame: Baseline and Day 14 (Morning)
measure: Change From Baseline in Speed of Memory as Measured by a Computerized Battery of Cognitive Tests on Day 14 (Morning)
timeFrame: Baseline and Day 14 (Morning)
measure: Change in Subjective Sleep Parameters From Day 14 as Compared to Day 17 as Measured by the Consensus Sleep Diary-Morning Administration (CSD-M):Self-Reported Sleep-Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and sTST
timeFrame: Day 14 to Day 17
measure: Change in Subjective Sleep Parameters From Day 14 as Compared to Day 17 Using Consensus Sleep Diary-Morning Administration: Subjective Refreshed Feeling on Waking (sFRESH) and Subjective Quality of Sleep (sQUAL)
timeFrame: Day 14 to Day 17
measure: Change in Subjective Sleep Parameters From Day 14 as Compared to Day 17 Using Consensus Sleep Diary-Morning Administration (CSD-M): Number of Nighttime Awakenings (s-nNAW)
timeFrame: Day 14 to Day 17
measure: Number of Participants With Withdrawal Symptoms of JNJ-42847922 as Measured by Physician Withdrawal Checklist (PWC) From Day 14 to Day 17
timeFrame: Day 14 to Day 17
measure: Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ) Total Score for Self-Assessment of Withdrawal Symptoms on Day 17
timeFrame: Day 17
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Preferred Research Partners
state: Arkansas
city: Rogers
country: United States
facility: Woodland Research Northwest
state: Arkansas
city: Anaheim
country: United States
facility: California Research Trials DBA Orange Country Research Institute
state: California
city: Oceanside
country: United States
facility: Excell Research Inc
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Upland
country: United States
facility: Empire Clinical Research, LLC
state: California
city: Clearwater
country: United States
facility: St. Francis Medical Institute
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Lake City
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Lauderhill
country: United States
facility: Innovative Clinical Research Inc
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Atlanta
country: United States
facility: NeuroTrials Research, Inc.
state: Georgia
city: Chicago
country: United States
facility: Chicago Research Center
state: Illinois
city: Elkridge
country: United States
facility: Centennial Medical Group
state: Maryland
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada
state: Nevada
city: Gastonia
country: United States
facility: Gastonia Medical Specialty Clinic
state: North Carolina
city: Mooresville
country: United States
facility: Clinical Research of Lake Norman
state: North Carolina
city: Cincinnati
country: United States
facility: CTI Clinical Trial and Consulting Services
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Mount Pleasant
country: United States
facility: Clinical Research of Charleston
state: South Carolina
city: Austin
country: United States
facility: FutureSearch Trials of Neurology, LP
state: Texas
city: Alken
country: Belgium
facility: Anima
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Wilrijk
country: Belgium
facility: Universiteit Antwerpen
city: Isere
country: France
facility: CHU de Grenoble Hopital Albert Michallon
city: Lyon Cedex 4
country: France
facility: Hopital de La Croix Rousse
city: Paris
country: France
facility: Hôpital Hôtel Dieu - Paris
city: Rouffach
country: France
facility: Centre Hospitalier Specialisé de Rouffach
city: Berlin
country: Germany
facility: Advanced Sleep Research GmbH
city: Berlin
country: Germany
facility: Emovis GmbH
city: Frankfurt
country: Germany
facility: Synexus Clinical Research GmbH
city: Hamburg
country: Germany
facility: CTC North GmbH & Co. KG
city: Sachsen
country: Germany
facility: Synexus Clinical Research GmbH
city: Schwerin
country: Germany
facility: Somni Bene GmbH
city: Schwerin
country: Germany
facility: Klinische Forschung Schwerin GmbH
city: Fukuoka-shi
country: Japan
facility: SOUSEIKAI PS Clinic
city: Kitakyushu-shi
country: Japan
facility: You Ariyoshi Sleep Clinic
city: Kochi-shi
country: Japan
facility: Takedakai Kochi Kagamigawa Hospital
city: Kurume-shi
country: Japan
facility: Kurume University Hospital
city: Nagoya-shi
country: Japan
facility: National Hospital Organization Nagoya Medical Center
city: Osaka-shi
country: Japan
facility: Gokeikai Osaka Kaisei Hospital
city: Otaru-shi
country: Japan
facility: Wellness Boyodai Hospital
city: Shibuya-ku
country: Japan
facility: Suimin Sogo Care Clinic Yoyogi
city: Shinjuku-ku
country: Japan
facility: Shinjuku Research Park Clinic
city: Toshima-ku
country: Japan
facility: Sekino Hospital
city: Tsu-shi
country: Japan
facility: Mie University Hospital
city: Yokohama-shi
country: Japan
facility: Kaiseikai Kita Shin Yokohama Internal Medicine Clinic
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych PI House sp z o o
city: Katowice
country: Poland
facility: NZOZ Wielospecjalistyczna Poradnia Lekarska 'Synapsis'
city: Poznan
country: Poland
facility: Osrodek Badan Klinicznych CROMED
city: Wroclaw
country: Poland
facility: EMC Instytut Medyczny SA
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: