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

The NPI-12, measure of psychobehavioral disturbances assessed frequency and severity of disturbances in 12 domains, based on a caregiver interview. Frequency for each domain was 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 product of frequency and severity scores, such that each domain was scored from 1 to 12. The NPI-12 total score was the sum of 12 domain scores, ranging from 0 (best) to 144 (worst), higher score represented greater frequency and worst severity of the symptoms. NPI-C was an instrument developed on basis of original NPI that gives a score based on product of frequency and severity ratings of 12 symptom domains that were summed to a total score. NPI-C domains: agitation and aggression NPI-C A+A were scored based on both caregiver and participant interviews and score ranged from 0 (does not occur) to 63 (severe). Higher scores indicated more severity.

The NPI-12, measure of psychobehavioral disturbances assessed frequency and severity of disturbances in 12 domains, based on a caregiver interview. Frequency for each domain was 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 product of frequency and severity scores, such that each domain was scored from 1 to 12. The NPI-12 total score was the sum of 12 domain scores, ranging from 0 (best) to 144 (worst), higher score represented greater frequency and worst severity of the symptoms. NPI-C was 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 were summed to a total score. NPI-C domains: agitation and aggression NPI-C A+A were scored based on both caregiver and participant interviews and score ranged from 0 (does not occur) to 63 (severe). Higher scores indicated more severity.

The CMAI-C, 37-item scale, measured the ability of a drug to reduce overall frequency of agitation symptoms, including aggressive behaviors. Individual items were rated by the clinician on a scale of 1 (never) to 7 (several times per hour) in which higher score represented the most frequent for each item assessed. CMAI-C total score was a sum of all categories that ranged from 37 (never) to 259 (several times), where higher score indicated greater severity.

SDI: based on caregiver (CG) interview and expanded version of item 11 (night-time behavioral disturbances) of NPI-12. It described frequency, severity and CG burden of sleep-disturbed behaviors for period prior to its administration. It consisted of 7 sub-questions from NPI-12 sleep disturbance item. Each sub-question was made into separate questions with frequency, severity, and CG distress rated with respect to participant. SDI score derived after CG rated frequency, severity of each of 7 separate sleep disturbance symptoms. CG distress ratings were not part of SDI total score, but distress was measured. Frequency scored on scale of 0 (not present) to 4 (once or more per day), severity scored on scale of 0 (not present) to 3 (occurrence of nighttime behaviors) and CG distress rated on scale of 0 (not at all) to 5 (extremely). SDI average total score=average frequency of item 1 to 7 multiplied with average severity of items 1 to 7; ranged from 0 to 12; higher score=greater severity.

The pharmacokinetic (PK) sample collection was done based on the availability of the participants either on Day 15 or 43 and thus collected data were analyzed and summary data were reported in this outcome measure. Plasma samples were analyzed using liquid chromatography/mass spectrometry/mass spectrometry (LC-MS/MS) method.