Clinical Trials/NCT03375203

NCT03375203

Completed

Phase 2

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

Janssen Research & Development, LLC55 sites in 5 countries365 target enrollmentNovember 23, 2017

ConditionsInsomnia Disorders

InterventionsPlacebo JNJ-42847922, 5 mg JNJ-42847922, 10 mg JNJ-42847922, 20 mg Zolpidem

DrugsPlacebo JNJ-42847922, 5 mg JNJ-42847922, 10 mg JNJ-42847922, 20 mg Zolpidem

Overview

Phase: Phase 2
Intervention: Placebo
Conditions: Insomnia Disorders
Sponsor: Janssen Research & Development, LLC
Enrollment: 365
Locations: 55
Primary Endpoint: Change From Baseline in Latency to Persistent Sleep (LPS) as Measured by Polysomnography (PSG) on Night 1
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

November 23, 2017

End Date

April 3, 2019

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Janssen Research & Development, LLC

Responsible Party

Sponsor

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
•(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:
•QT interval corrected according to Fridericia's formula: \>= 450 millisecond (msec) (males); \>= 470 msec (females).
•Evidence of 2nd and 3rd degree atrioventricular block, or 1st degree atrioventricular block with PR interval \>210 msec, left bundle branch block.
•Features of new ischemia.
•Other clinically important arrhythmia
•Has significant hypersomnia not related to night time insomnia (based on clinical judgment of the investigator)

Arms & Interventions

Placebo

Participants will receive matching placebo to JNJ-42847922 as oral capsules at normal study bedtime on Nights 1 through 14.

Intervention: Placebo

JNJ-42847922 5 milligram (mg)

Participant will receive JNJ-42847922 5 mg dose as oral capsules at normal study bedtime on Nights 1 through 14.

Intervention: JNJ-42847922, 5 mg

JNJ-42847922 10 mg plus Placebo

Participant will receive JNJ-42847922 10 mg as oral capsule and one placebo capsule at normal study bedtime on Nights 1 through 14.

Intervention: Placebo

JNJ-42847922 10 mg plus Placebo

Participant will receive JNJ-42847922 10 mg as oral capsule and one placebo capsule at normal study bedtime on Nights 1 through 14.

Intervention: JNJ-42847922, 10 mg

JNJ-42847922 20 mg plus Placebo

Participant will receive JNJ-42847922 20 mg as oral capsule and one placebo capsule at normal study bedtime on Nights 1 through 14.

Intervention: Placebo

JNJ-42847922 20 mg plus Placebo

Participant will receive JNJ-42847922 20 mg as oral capsule and one placebo capsule at normal study bedtime on Nights 1 through 14.

Intervention: JNJ-42847922, 20 mg

Zolpidem plus Placebo

Participants will receive Zolpidem 5 mg plus one placebo capsule or 10 mg dose as oral capsule at normal study bedtime on Nights 1 through 14.

Intervention: Placebo

Zolpidem plus Placebo

Participants will receive Zolpidem 5 mg plus one placebo capsule or 10 mg dose as oral capsule at normal study bedtime on Nights 1 through 14.

Intervention: Zolpidem

Outcomes

Primary Outcomes

Change From Baseline in Latency to Persistent Sleep (LPS) as Measured by Polysomnography (PSG) on Night 1

Time Frame: Baseline and Night 1

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.

Secondary Outcomes

Change From Baseline in LPS as Measured by PSG on Night 13(Baseline and Night 13)
Change From Baseline in Wake After Sleep Onset (WASO) Over the First 6 Hours as Measured by PSG on Night 1(Baseline and over first 6 hours on Night 1)
Change From Baseline in WASO Over the First 6 Hours as Measured by PSG on Night 13(Baseline and over first 6 hours on Night 13)
Change From Baseline in Total Sleep Time (TST) as Measured by PSG Over 6 Hours on Nights 1 and 13(Baseline, Over 6 hours on Nights 1 and 13)
Change From Baseline in Sleep Efficiency (SE) Measured by PSG on Nights 1 and 13(Baseline, Nights 1 and 13)
Change From Baseline in Total Sleep Time (TST) as Measured by PSG Over 8 Hours on Nights 1 and 13(Baseline, Over 8 hours on Nights 1 and 13)
Change From Baseline in Wake After Sleep Onset (WASO) Measured Hourly on Days 1 and 13 From Hour 1 to Hour 8(Baseline, Days 1 and 13 (Hours 1 to 8))
Change From Baseline in Wake During Total Sleep Period on Day 1 and 13(Baseline, Day 1 and 13)
Change From Baseline in Time to First Awakening After Sleep on Day 1 and 13(Baseline, Day 1 and 13)
Change From Baseline in Number of Night-time Awakenings (nNAW) Over 6 Hours on Day 1 and 13(Baseline, Over 6 hours on Day 1 and 13)
Change From Baseline in Number of Night-time Awakenings Per Hour (nNAW/hr) on Day 1 and 13(Baseline, Day 1 and 13)
Change From Baseline in Wake After Final Awakening on Day 1 and 13(Baseline, Day 1 and 13)
Change From Baseline in Rapid Eye Movement (REM) Duration on Day 1 and 13(Baseline, Day 1 and 13)
Change From Baseline in Rapid Eye Movement (REM) Latency on Day 1 and 13(Baseline, Day 1 and 13)
Percentage of Participants With Sleep-Onset Rapid Eye Movement on Day 1 and 13(Day 1 and 13)
Change From Baseline in Total Time Spent in Non-Rapid Eye Movement Sleep on Day 1 and 13(Baseline, Day 1 and 13)
Percentage of Participants Who Achieved Remission Based on Insomnia Severity Index (ISI) Total Score on Day 14 - Observed Case(Day 14)
Change From Baseline in Clinician's Assessment of Insomnia Severity Using the Clinical Global Impression - Severity (CGI-S) Score on Day 14(Baseline and Day 14)
Number of Participants With Clinically Significant Vital Signs and Physical Abnormalities(Up to Day 15)
Change From Baseline in Quality of Working Memory as Measured by a Computerized Battery of Cognitive Tests on Day 14 (Morning)(Baseline and Day 14 (Morning))
Change From Baseline in Number of Sleep Cycles on Day 1 and 13(Baseline, Day 1 and 13)
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)(Baseline, Days 2 and 14)
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)(Baseline, Days 2 and 14)
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)(Baseline, Days 2 and 14)
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(Baseline, Days 8 and 14)
Participant's Assessment of Improvement in Insomnia Using the Patient Global Impression - Improvement (PGI-I) Scale Score on Day 14(Baseline and Day 14)
Percentage of Participants Who Achieved Response Based on Insomnia Severity Index (ISI) Total Score on Day 14 - Observed Case(Day 14)
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(Baseline, Days 8 and 14)
Change From Baseline in Participant's Assessment of Insomnia Severity Using the Patient Global Impression - Severity (PGI-S) Scale Score on Day 14(Baseline and Day 14)
Change From Baseline in Clinician's Assessment of Insomnia Improvement Using Clinical Global Impression-Improvement (CGI-I) Score on Day 14(Baseline and Day 14)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability(Up to Day 17)
Number of Participants With Treatment-Emergent Serious Adverse Events and Events of Special Interest(Up to Day 17)
Number of Participants With Withdrawal Symptoms of JNJ-42847922 as Measured by Physician Withdrawal Checklist (PWC) From Day 14 to Day 17(Day 14 to Day 17)
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities(Up to Day 14)
Number of Participants With Clinically Significant Laboratory Abnormalities(Up to Day 15)
Number of Participants With Suicidal Ideation and Behavior as Determined by Columbia Suicide Severity Rating Scale (C-SSRS) Score(Day 14)
Change From Baseline in Karolinska Sleepiness Scale (KSS) Total Score on Days 2 and 14(Baseline, Days 2 and 14)
Postural Stability Measured by Ataxiameter(Day 14 (morning))
Change From Baseline in Power of Attention as Measured by a Computerized Battery of Cognitive Tests on Day 14 (Morning)(Baseline and Day 14 (Morning))
Change From Baseline in Continuity of Attention as Measured by a Computerized Battery of Cognitive Tests on Day 14 (Morning)(Baseline and Day 14 (Morning))
Change From Baseline in Quality of Episodic Secondary Memory as Measured by a Computerized Battery of Cognitive Tests on Day 14 (Morning)(Baseline and Day 14 (Morning))
Change From Baseline in Speed of Memory as Measured by a Computerized Battery of Cognitive Tests on Day 14 (Morning)(Baseline and Day 14 (Morning))
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)(Day 14 to Day 17)
Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ) Total Score for Self-Assessment of Withdrawal Symptoms on Day 17(Day 17)
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(Day 14 to Day 17)
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)(Day 14 to Day 17)