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.

Time frame: Baseline (Day 1) and Day 43

Population: Full analysis set (FAS) included all randomized participants who took at least 1 dose of study intervention. 'N' (number of participants analyzed): participants evaluable for this outcome measure. Estimand 1 used to analyze benefit from seltorexant 20 mg versus placebo in adults and elderly participants with probable Alzheimer's disease (AD) with clinically significant agitation/aggression who took study intervention as directed and regardless treatment discontinuation without treatment switch.

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.

Time frame: Baseline (Day 1) and Day 43

Population: Full analysis set (FAS) included all randomized participants who took at least 1 dose of study intervention. 'N' (number of participants analyzed): participants evaluable for this outcome measure. Estimand 2 was used to analyze benefit from seltorexant 20 mg versus placebo in adults and elderly participants with probable AD with clinically significant agitation/aggression who took study intervention as directed and regardless of treatment discontinuation without treatment switch.

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.

Time frame: Baseline (Day 1) and Day 43

Population: FAS included all randomized participants who took at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies participants who were evaluable for this outcome measure.

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.

Time frame: Baseline and Day 43

Population: FAS included all randomized participants who took at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies participants who were evaluable for this outcome measure.

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.

Time frame: Either Day 15 (8 and 14 hours post dose on night of Day 14) or Day 43 (8 and 14 hours post dose on night of Day 42)

Population: The PK analysis set included all randomized participants to the seltorexant treatment group and with at least one PK sample taken. Here, 'N' (overall number of participants analyzed) signifies participants who were evaluable for this outcome measure.