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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 2

Conditions: Insomnia Disorders

Treatments: Drug: Placebo; Drug: Zolpidem; Drug: JNJ-42847922, 20 mg; Drug: JNJ-42847922, 10 mg; Drug: JNJ-42847922, 5 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT03375203

42847922ISM2005 (Other Identifier)

2017-000980-33 (EudraCT Number)

CR108427

Details and patient eligibility

About

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.

Enrollment: 365 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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365 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

JNJ-42847922 5 milligram (mg)

Experimental group

Description:

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

Treatment:

Drug: JNJ-42847922, 5 mg

JNJ-42847922 10 mg plus Placebo

Experimental group

Description:

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

Treatment:

Drug: JNJ-42847922, 10 mg

Drug: Placebo

JNJ-42847922 20 mg plus Placebo

Experimental group

Description:

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

Treatment:

Drug: JNJ-42847922, 20 mg

Drug: Placebo

Zolpidem plus Placebo

Experimental group

Description:

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.

Treatment:

Drug: Zolpidem

Drug: Placebo