Sub-Lingual Dexmedetomidine in Agitation Associated With Dementia

The onset and magnitude of calming effects of different doses of BXCL501 on symptoms of acute agitation associated with dementia was described as measured by the PAS. The PAS is an instrument that measured 4 behaviors namely: aberrant vocalization, motor agitation, aggressiveness and resisting to care. The patients are evaluated on a scale of 0 to 4, where 0 indicated no agitation and 4 indicated highest form of agitation. The PAS total score ranges from 0 to 16. Higher scores mean a worse outcome. Change in value of PAS total score, with negative value indicated the improvement in condition of the patients.

To evaluate the change in the total score of ACES from baseline to 8 hours post administration of 30 mcg, 60 mcg and 40 mcg compared to placebo. The ACES is a single item measure rating overall agitation and sedation which ranges from 1 to 9, where 1 indicates marked agitation, 2 - moderate agitation; 3 - mild agitation; 4 - normal behavior; 5 - mild calmness; 6 - moderate calmness; 7 - marked calmness; 8 - deep sleep; and 9 - unarousable. Change from baseline (pre-dose) ACES total score, with negative values in favor of improvement.

The change in PEC score was evaluated following the administration of the BXCL501 60 mcg, and BXCL501 30 mcg (for Part A) and BXCL501 40 mcg (for Part B) versus placebo. PEC is the sum of 5 subscales (poor impulse control, tension, hostility, uncooperativeness, and excitement, each subscale ranging from 1 to 7) and thus ranges from 5 to 35. Change from baseline (pre-dose) PEC total score, with negative values is in favor of improvement.

The Number of patients who achieved a 40%reduction in total PEC score from baseline at 2 hours following administration of BXCL501 30 mcg, 60 mcg (for Part A) and BXCL501 40 mcg (for Part B) compared to placebo were evaluated. Responder defined as achieving >= 40% reduction in PEC from baseline (pre-dose). The change from baseline in (pre-dose) PEC total score is presented for the Primary Outcome above.

The CGI-S was based upon the severity of agitation. It was assessed based on the following scale: 0 = Not assessed; 1 = Normal not at all symptomatic; 2 = Minimally symptomatic- few or mild symptoms -little interference with patients functioning; 3 = Mildly symptomatic-low level of symptoms-little interference in social functioning; 4 = Moderately symptomatic-some prominent symptoms-some interference in functioning; 5 = Markedly symptomatic-significant symptoms with very substantial interference in functioning; 6 = Severely symptomatic- very marked symptoms make it difficult for patients to engage with others; 7 = Among the most extremely symptomatic patients-extreme symptoms -patient is incapacitated or highly dangerous to self or others requires extra care and supervision. The higher the score, the higher is the severity of the agitation and lesser the score, the lower the agitation. Change from baseline CGIS total score, with negative values in favor of improvement.

To evaluate the CGI-I agitation score at 30 minutes, 1 hour, 2 hours, and 8 hours after administration of 30 mcg, 60 mcg and 40 mcg of BXCL501 compared to placebo. The CGI-I scores range from 1 to 7 comprise of 0 = Not assessed (missing), 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. The lower score (1) indicated the improvement in the condition of patient and higher score (7) indicates the worsening of the condition. Straight CGI-I total score, with lower values in favor of improvement.

To evaluate the change in Cohen Mansfield Agitation Inventory (CMAI) total score from baseline after 2 hour and on Day 7 post administration of 30 mcg, 60 mcg and 40 mcg BXCL501 compared to placebo. The CMAI is a rating which is comprised of 29 behaviors each rated on a 7-point scale of frequency. A total CMAI score is obtained by summing all the individual items, giving a range from 29 to 203. Change from baseline (pre-dose) CMAI total score, with negative values in favor of improvement in the condition of the patients.

To evaluate the time taken for BXCL501 30 mcg, 60mcg, 90 mcg and 40 mcg compared to placebo to dissolve which was measured after 30 minutes of administration.

To evaluate the number patient showing negative reactions to sublingual film by assessing the buccal at 30 minutes, 2 hours, 4 hours and 24 hours post administration of 30mcg, 60 mcg, 40 mcg and 90 mcg v/s placebo. The larger number of patients reporting negative reaction, the lesser is the reliability of the drug.

To evaluate the change in PANSS Supplementary Items Total Score from Baseline to 2 hours post administration of 40 mcg of BXCL501 compared to placebo. PANSS Supplementary Items: The total score (sum score of anger, difficulty in delaying gratification, and affective lability) ranges from 3 to 21. The higher score indicates the worsening of the condition and lower score indicates the improvement of the condition of the patient. Change from baseline (pre-dose) PANSS Supplementary Items total score, with negative values in favor of improvement.