A Study of Seltorexant in Participants With Probable Alzheimer's Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the effect of seltorexant versus placebo on the sum of Agitation and Aggression domain scores (A plus A) of the Neuropsychiatric Inventory-Clinician rating (NPI-C) in participants with probable Alzheimer's Disease (AD) with clinically significant agitation/aggression.

Official Title
-----------------
A Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Investigate the Safety, Tolerability, and Clinical Efficacy of Seltorexant (JNJ-42847922) on Behavioral and Psychological Symptoms of Dementia in Patients With Probable Alzheimer's Disease

Conditions
-----------------
Alzheimer Disease

Intervention / Treatment
-----------------
* Drug: Seltorexant
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant has received a diagnosis of probable Alzheimer Disease (AD) (Diagnostic and Statistical Manual of Mental Disorders-5 [DSM-5]) with the following characteristics at screening: Clinical Dementia Rating (CDR) global score greater than or equal to (>=) 1; Mini-Mental State Examination (MMSE) total score of 10 to 24 (inclusive) Participant meets the criteria of a syndrome diagnosis of agitation based on International Psychogeriatric Association (IPA) consensus clinical and research definition of agitation in cognitive disorders for at least 2 weeks before screening Participant meets the criteria of Neuropsychiatric Inventory (NPI-12) Agitation/Aggression (A/A) domain score >= 4 with frequency score >= 2 at screening and baseline with no more than 35 percent (%) of improvement in NPI-12 A/A domain score from the screening to baseline assessments Female participants must be postmenopausal before study entry (amenorrhea for at least 12 months) Body Mass Index (BMI) within the range 18-40 kilograms per square meter (kg/m^2) (inclusive) Exclusion Criteria: Participant fulfils diagnostic criteria for non-Alzheimer's Dementia: example, Frontotemporal Dementia (FTD), Diffuse Lewy Body Dementia (DLBD), and post-stroke dementia, based on clinical history. (Participants may be included with mixed AD/vascular dementia) Participant has a clinically significant acute illness within 7 days prior to study intervention administration Participants with a history of delirium within 30 days prior to or during screening Participant with a cause of agitation that is not secondary to dementia (such as pain) or significant history of aggression prior to dementia based on investigator judgment Participants who are not stable on concomitant medications or take prohibited medications

Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Seltorexant<br>Participants will receive single oral dose of seltorexant 20 milligrams (mg) tablet once daily from Day 1 to Day 42. | Drug: Seltorexant<br>* Seltorexant 20 mg will be administered orally as a tablet.<br>* Other names: JNJ-42847922;|
| Placebo Comparator: Placebo<br>Participants will receive single oral dose of matching placebo tablet once daily from Day 1 to Day 42. | Drug: Placebo<br>* Matching placebo will be administered orally as a tablet.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Neuropsychiatric Inventory-Clinician Rating (NPI-C) Agitation and Aggression (A plus A) Scores | The NPI-12 is a measure of psychobehavioral disturbances assessing the frequency and severity of disturbances in 12 domains, based on a caregiver interview. Frequency for each domain is rated on a 4-point scale (from 1=rarely to 4=very often) and severity on a 3-point scale (from 1=mild to 3=severe), with the score for each domain being the product of the frequency and severity scores, such that each domain is scored from 1 to 12. The NPI-12 total score is the sum of the 12 domain scores, ranging from 0 (best) to 144 (worst). NPI-C is an instrument developed on the basis of original NPI that gives a score based on product of frequency and severity ratings of 12 symptom domains that can then be summed to a total score. Five domains will be measured in the study with NPI-C: Delusions, Hallucinations, Agitation, Aggression, Dysphoria, and will include both caregiver and participant interviews. Higher scores on the NPI-C are associated with a greater clinical severity of symptoms. | Baseline up to Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on the Total Cohen-mansfield Agitation Inventory-Community Version (CMAI-C) Score | The CMAI-C is a 37-item scale that measures the ability of a drug to reduce overall frequency of agitation symptoms, including aggressive behaviors. Individual items are rated on a scale of 1 (never) to 7 (several times per hour) in which a score of 7 represents the most frequent for each item assessed. The total score is a sum of all categories that ranges form 37-259, where higher score indicates greater severity. | Baseline up to Day 43 | 
| Change from Baseline in Sleep Disorder Inventory (SDI) Total Score | SDI is based on a caregiver interview and an expanded version of one item of the NPI-12. It describes the frequency, severity, and caregiver burden of sleep-disturbed behaviors during a period prior to its administration. The SDI total score ranges from 0-12 where higher score indicates greater severity. | Baseline up to Day 43 | 
| Plasma Concentrations of Seltorexant and its Metabolite | Plasma samples will be analyzed to measure concentrations of seltorexant and its metabolite using a validated, specific, and sensitive Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC- MS/MS) method. | Day 15 and Day 43 |