Agitation,Psychomotor, Dementia
Conditions
Brief summary
This is an adaptive Phase 1b/2 trial design. It is randomized, double-blind, placebo-controlled, multiple ascending dose study assessing efficacy, pharmacokinetics, safety and tolerability of BXCL-501 dosing in adult (65 years and older) males and females with acute agitation associated with dementia. Evaluation of 3 doses are planned.
Detailed description
This is a Phase 1b/2 randomized, double-blind, placebo controlled, ascending dose finding study assessing efficacy, pharmacokinetics, safety, and tolerability of BXCL501 with 3 dosing groups in adult (65 years and older) males and females with acute agitation associated with all forms of dementia. Evaluation of three (3) doses of sublingual BXCL 501 are planned. Cohort 1, Cohort 2 and Cohort 3 will be given 30µg, 60µg and 90µg dose respectively of BXCL501 or placebo. Subjects assigned to Cohort 3 will participate in a 1-week safety observation before being enrolled. This is an adaptive design as doses selected for testing may be different from these, based upon safety reviews. Doses lower or higher may be chosen to test, up to 180µg, and additional subjects may be added to a cohort. BXCL501 films may be divided in half if needed to deliver half-dose strengths. At least 30 subjects (10 per cohort) will be enrolled at up to 3 study sites in the United States. In Part B a total of 46 subjects will receive BXCL501 40 μg or matching placebo film. The effects of BXCL 501 on acute agitation will be assessed by the following scales: Pittsburgh Agitation Scale (PAS), the PANSS-EC (PEC), Cohen-Mansfield Agitation Inventory (CMAI), CGI-Severity for Agitation and CGI Improvement for Agitation. Adverse Events (AEs), clinical laboratory tests, ECG, and vital signs will be monitored, and all observed.
Interventions
DRUGSublingual film containing Dexmedetomidine
Sublingual film containing Dexmedetomidine
DRUGSublingual Placebo Film
Sublingual placebo film that matches BXCL501
Sponsors
BioXcel Therapeutics Inc
Cognitive Research Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) This is a double-blind study. Due to the nature of the drug, the pharmacist and the drug administrator will both be aware of the treatment. They have no other responsibility in the trial
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female patients 65 years and older. * Patients who have dementia and a history of acute agitation. * History of agitation that requires intervention or impairs social or daily activities * Patients who meet International Psychogeriatric Association (IPA) diagnostic criterion for agitation. * Patients with a total score of ≥ 8 on the Pittsburgh Agitation Scale (PAS). * Patients who have a score of ≥ 2 on at least 1 of the 4 items on the Pittsburgh Agitation Scale (PAS). * Patients who read, understand and provide written informed consent, or who have a Legally Authorized Representative (LAR). * Patients who are in good general health.
Exclusion criteria
* For Part B: Patients with dementia associated with Parkinson's disease and/or Lewy Body Disease, if etiology of dementia is known. * Patients with agitation caused by acute intoxication. * Patients treated within 4 hours prior to study drug administration with benzodiazepines, other sedatives, hypnotics or oral or short-acting intramuscular antipsychotics must be excluded. * Treatment with alpha-1 noradrenergic blockers, alpha adrenergic antagonists within 8 hours prior to dosing. * No new chronic medications initiated in the past 14 days prior to screening excluding over-the-counter products taken sporadically. * Patients at significant risk of harm to themselves or others * Patients considered medically unstable or in recovery * Patients with history of clinically significant syncope or syncopal attacks, orthostatic hypotension within the past 2 years, current evidence of hypovolemia, orthostatic hypotension. * Cohort 3 only: Patients who are taking nitrates or beta blockers shall be excluded. Any other anti-hypertensives should be maintained in the course of the study. * Patients who have received an investigational drug within 30 days prior to the current agitation episode must be excluded. * Patients experiencing clinically significant pain, per Investigator. * Cohort 3 only: Patients who are a high fall risk assessed via the Johns Hopkins Fall Risk Assessment (total score \>13) or during the 1-week safety observation period * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Positive and Negative Syndrome Scale-Excited Component (PEC) Total Score | Baseline and 2 hours post-dose | The change in PEC score was evaluated at 2 hours 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. |
| Number of Patients With Adverse Events | Day 7 post dose | The safety and tolerability of single doses of BXCL501 was determined in treatment of acute agitation associated with dementia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | Baseline and at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, Day 3, Day 7 post-dose | 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. |
| Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | Baseline and 1 hour, 2 hours, 4 hours, 8 hours post-dose | 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. |
| Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Baseline and at 30 minutes, 1 hour, 4 hours, 8 hours, 24 hours, Day 3 and Day 7 post-dose | 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. |
| Number of Patients at Each Dose Who Achieve a 40% Reduction From Baseline in PEC Total Score at 2 Hours Post-dose ("Responders") | Baseline and 2 hours post-dose | 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. |
| Change in Clinician Global Impression of Severity (CGI-S) Agitation Score From Baseline | Baseline and at 2 hours, and 24 hours post-dose | 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. |
| Clinical Global Impression - Improvement (CGI-I) Agitation Score | 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours post-dose | 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. |
| Change in Cohen Mansfield Agitation Inventory (CMAI) Total Score From Baseline | Baseline and at 2 Hours and Day 7 post-dose | 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. |
| Number of Patients With Event "Time Taken for Medication to Dissolve" | At 30 minutes post-dose | 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. |
| Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | At 30 minutes, 2 hours, 4 hours, 24 hours post dose | 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. |
| Part B: Change From Baseline in the Total Score of 3 Supplementary Items of Positive and Negative Syndrome Scale (PANSS) | Baseline and at 2 hours post-dose | 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. |
Countries
United States
Contacts
STUDY_CHAIRBioXcel MM, MD
BioXcel Therapeutics
Participant flow
Recruitment details
The trial was conducted at 4 sites in the United States from 27 December 2019 to 24 January 2022.
Pre-assignment details
All the assessments were performed as per the schedule of the assessments.
Participants by arm
| Arm | Count |
|---|---|
| Part A-30 mcg BXCL501 Randomized patients self-administered 30 mcg of BXCL501 sublingually under the supervision of a trained staff member. | 16 |
| Part A-60 mcg BXCL501 Randomized patients self-administered 60 mcg BXCL501 sublingually under the supervision of a trained staff member. | 20 |
| Part A- 90 mcg BXCL501 Randomized patients self-administered 90 mcg BXCL501 sublingually under the supervision of a trained staff member. | 4 |
| Part A-Placebo Randomized patients self-administered Placebo sublingually under the supervision of a trained staff member. | 14 |
| Part B-40 Mcg-BXCL501 Randomized patients self-administered 40 mcg BXCL501 sublingually under the supervision of a trained staff member. | 23 |
| Part B-Placebo Randomized patients self-administered Placebo sublingually under the supervision of a trained staff member. | 23 |
| Total | 100 |
Baseline characteristics
| Characteristic | Part A-30 mcg BXCL501 | Part A-60 mcg BXCL501 | Part A- 90 mcg BXCL501 | Part A-Placebo | Part B-40 Mcg-BXCL501 | Part B-Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 75.8 Years STANDARD_DEVIATION 8 | 77.7 Years STANDARD_DEVIATION 6.4 | 68.8 Years STANDARD_DEVIATION 7.9 | 75.9 Years STANDARD_DEVIATION 8.9 | 77.4 Years STANDARD_DEVIATION 8.2 | 77.3 Years STANDARD_DEVIATION 8.6 | 76.6 Years STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 8 Participants | 7 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 18 Participants | 4 Participants | 14 Participants | 15 Participants | 16 Participants | 83 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants | 1 Participants | 5 Participants | 5 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 14 Participants | 1 Participants | 13 Participants | 17 Participants | 18 Participants | 76 Participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 0 Participants | 8 Participants | 8 Participants | 11 Participants | 42 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 4 Participants | 6 Participants | 15 Participants | 12 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 20 | 0 / 4 | 0 / 14 | 1 / 23 | 0 / 23 |
| other Total, other adverse events | 11 / 16 | 14 / 20 | 4 / 4 | 0 / 14 | 12 / 23 | 2 / 23 |
| serious Total, serious adverse events | 0 / 16 | 0 / 20 | 0 / 4 | 0 / 14 | 1 / 23 | 0 / 23 |
Outcome results
Primary
Mean Change From Baseline in Positive and Negative Syndrome Scale-Excited Component (PEC) Total Score
The change in PEC score was evaluated at 2 hours 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.
Time frame: Baseline and 2 hours post-dose
Population: The Intent to Treat Population consisted of all patients in the Safety Population who have a baseline and at least one post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A-30 mcg BXCL501 | Mean Change From Baseline in Positive and Negative Syndrome Scale-Excited Component (PEC) Total Score | -5.4 score on a scale | Standard Deviation 3.4 |
| Part A-60 mcg BXCL501 | Mean Change From Baseline in Positive and Negative Syndrome Scale-Excited Component (PEC) Total Score | -7.1 score on a scale | Standard Deviation 3.8 |
| Part A-Placebo | Mean Change From Baseline in Positive and Negative Syndrome Scale-Excited Component (PEC) Total Score | -2.9 score on a scale | Standard Deviation 2.7 |
| Part B-40 Mcg-BXCL501 | Mean Change From Baseline in Positive and Negative Syndrome Scale-Excited Component (PEC) Total Score | -6.8 score on a scale | Standard Deviation 5.1 |
| Part B-Placebo | Mean Change From Baseline in Positive and Negative Syndrome Scale-Excited Component (PEC) Total Score | -1.8 score on a scale | Standard Deviation 4.4 |
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (2 hours)p-value: 0.0813Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (2 hours)p-value: 0.0011Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (2 hours)p-value: 0.0002Mixed effects model
Primary
Number of Patients With Adverse Events
The safety and tolerability of single doses of BXCL501 was determined in treatment of acute agitation associated with dementia.
Time frame: Day 7 post dose
Population: The safety population consisted of all patients who received study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A-30 mcg BXCL501 | Number of Patients With Adverse Events | 11 Participants |
| Part A-60 mcg BXCL501 | Number of Patients With Adverse Events | 14 Participants |
| Part A-90 mcg BXCL501 | Number of Patients With Adverse Events | 4 Participants |
| Part A-Placebo | Number of Patients With Adverse Events | 0 Participants |
| Part B-40 Mcg-BXCL501 | Number of Patients With Adverse Events | 12 Participants |
| Part B-Placebo | Number of Patients With Adverse Events | 2 Participants |
Secondary
Change in Clinician Global Impression of Severity (CGI-S) Agitation Score From Baseline
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.
Time frame: Baseline and at 2 hours, and 24 hours post-dose
Population: The Intent to Treat Population consisted of all patients in the Safety Population who have a baseline and at least one post-baseline efficacy assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-30 mcg BXCL501 | Change in Clinician Global Impression of Severity (CGI-S) Agitation Score From Baseline | 2 hours | -1.3 score on a scale | Standard Deviation 0.8 |
| Part A-30 mcg BXCL501 | Change in Clinician Global Impression of Severity (CGI-S) Agitation Score From Baseline | 24 hours | -1.4 score on a scale | Standard Deviation 1.1 |
| Part A-60 mcg BXCL501 | Change in Clinician Global Impression of Severity (CGI-S) Agitation Score From Baseline | 2 hours | -2.1 score on a scale | Standard Deviation 0.9 |
| Part A-60 mcg BXCL501 | Change in Clinician Global Impression of Severity (CGI-S) Agitation Score From Baseline | 24 hours | -1.6 score on a scale | Standard Deviation 0.9 |
| Part A-Placebo | Change in Clinician Global Impression of Severity (CGI-S) Agitation Score From Baseline | 2 hours | -0.9 score on a scale | Standard Deviation 0.9 |
| Part A-Placebo | Change in Clinician Global Impression of Severity (CGI-S) Agitation Score From Baseline | 24 hours | -1.2 score on a scale | Standard Deviation 1.1 |
| Part B-40 Mcg-BXCL501 | Change in Clinician Global Impression of Severity (CGI-S) Agitation Score From Baseline | 24 hours | -1.2 score on a scale | Standard Deviation 1.1 |
| Part B-40 Mcg-BXCL501 | Change in Clinician Global Impression of Severity (CGI-S) Agitation Score From Baseline | 2 hours | -2.2 score on a scale | Standard Deviation 1.3 |
| Part B-Placebo | Change in Clinician Global Impression of Severity (CGI-S) Agitation Score From Baseline | 2 hours | -0.7 score on a scale | Standard Deviation 1 |
| Part B-Placebo | Change in Clinician Global Impression of Severity (CGI-S) Agitation Score From Baseline | 24 hours | -0.7 score on a scale | Standard Deviation 1.2 |
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (2 hours)p-value: 0.0952Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 2; 24 hours)p-value: 0.8977Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 2 hours)p-value: 0.0002Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 2; 24 hours)p-value: 0.3147Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 2 hours)p-value: <0.0001Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 2; 24 hours)p-value: 0.1241Mixed effects model
Secondary
Change in Cohen Mansfield Agitation Inventory (CMAI) Total Score From Baseline
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.
Time frame: Baseline and at 2 Hours and Day 7 post-dose
Population: The Intent to Treat Population consisted of all patients in the Safety Population who have a baseline and at least one post-baseline efficacy assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-30 mcg BXCL501 | Change in Cohen Mansfield Agitation Inventory (CMAI) Total Score From Baseline | 2 hours | -8.9 score on a scale | Standard Deviation 5.1 |
| Part A-30 mcg BXCL501 | Change in Cohen Mansfield Agitation Inventory (CMAI) Total Score From Baseline | Day 7 | -5.9 score on a scale | Standard Deviation 4.3 |
| Part A-60 mcg BXCL501 | Change in Cohen Mansfield Agitation Inventory (CMAI) Total Score From Baseline | 2 hours | -14.7 score on a scale | Standard Deviation 9.8 |
| Part A-60 mcg BXCL501 | Change in Cohen Mansfield Agitation Inventory (CMAI) Total Score From Baseline | Day 7 | -6.6 score on a scale | Standard Deviation 6.7 |
| Part A-Placebo | Change in Cohen Mansfield Agitation Inventory (CMAI) Total Score From Baseline | 2 hours | 1.6 score on a scale | Standard Deviation 4.5 |
| Part A-Placebo | Change in Cohen Mansfield Agitation Inventory (CMAI) Total Score From Baseline | Day 7 | 0.4 score on a scale | Standard Deviation 9.8 |
| Part B-40 Mcg-BXCL501 | Change in Cohen Mansfield Agitation Inventory (CMAI) Total Score From Baseline | Day 7 | -6.9 score on a scale | Standard Deviation 17.7 |
| Part B-40 Mcg-BXCL501 | Change in Cohen Mansfield Agitation Inventory (CMAI) Total Score From Baseline | 2 hours | -17.9 score on a scale | Standard Deviation 22.7 |
| Part B-Placebo | Change in Cohen Mansfield Agitation Inventory (CMAI) Total Score From Baseline | 2 hours | -5.7 score on a scale | Standard Deviation 14 |
| Part B-Placebo | Change in Cohen Mansfield Agitation Inventory (CMAI) Total Score From Baseline | Day 7 | -1.4 score on a scale | Standard Deviation 4.5 |
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 7)p-value: 0.029Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 1; 2 hours)p-value: 0.0591Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 7)p-value: 0.0966Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 2 hours)p-value: <0.0001Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 2 hours)p-value: 0.0937Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 7)p-value: 0.2747Mixed effects model
Secondary
Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline
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.
Time frame: Baseline and at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, Day 3, Day 7 post-dose
Population: The Intent to Treat Population consisted of all patients in the Safety Population who have a baseline and at least one post-baseline efficacy assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-30 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 30 minutes | -1.3 score on a scale | Standard Deviation 1.2 |
| Part A-30 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 1 hour | -2.5 score on a scale | Standard Deviation 1.8 |
| Part A-30 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 2 hours | -3.9 score on a scale | Standard Deviation 2.4 |
| Part A-30 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 4 hours | -4.7 score on a scale | Standard Deviation 3.1 |
| Part A-30 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 8 hours | -4.4 score on a scale | Standard Deviation 3.2 |
| Part A-30 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 24 hours | -4.3 score on a scale | Standard Deviation 2.8 |
| Part A-30 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | Day 3 | -3.9 score on a scale | Standard Deviation 3.4 |
| Part A-30 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | Day 7 | -3.9 score on a scale | Standard Deviation 3.1 |
| Part A-60 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 2 hours | -5.8 score on a scale | Standard Deviation 2.1 |
| Part A-60 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 24 hours | -4.9 score on a scale | Standard Deviation 2.1 |
| Part A-60 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 30 minutes | -1.6 score on a scale | Standard Deviation 1.7 |
| Part A-60 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 4 hours | -6.4 score on a scale | Standard Deviation 1.3 |
| Part A-60 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 1 hour | -4.0 score on a scale | Standard Deviation 2.2 |
| Part A-60 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | Day 7 | -4.3 score on a scale | Standard Deviation 2.3 |
| Part A-60 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 8 hours | -6.2 score on a scale | Standard Deviation 1.7 |
| Part A-60 mcg BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | Day 3 | -4.9 score on a scale | Standard Deviation 2.4 |
| Part A-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | Day 3 | -3.7 score on a scale | Standard Deviation 3.4 |
| Part A-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | Day 7 | -3.3 score on a scale | Standard Deviation 2.7 |
| Part A-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 4 hours | -3.3 score on a scale | Standard Deviation 2.8 |
| Part A-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 24 hours | -3.9 score on a scale | Standard Deviation 2.4 |
| Part A-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 2 hours | -2.6 score on a scale | Standard Deviation 2.4 |
| Part A-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 1 hour | -2.1 score on a scale | Standard Deviation 1.8 |
| Part A-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 30 minutes | -1.3 score on a scale | Standard Deviation 1.6 |
| Part A-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 8 hours | -3.1 score on a scale | Standard Deviation 2 |
| Part B-40 Mcg-BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 1 hour | -4.7 score on a scale | Standard Deviation 3.2 |
| Part B-40 Mcg-BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 2 hours | -5.4 score on a scale | Standard Deviation 3.4 |
| Part B-40 Mcg-BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 4 hours | -5.2 score on a scale | Standard Deviation 3.7 |
| Part B-40 Mcg-BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 8 hours | -4.1 score on a scale | Standard Deviation 3.5 |
| Part B-40 Mcg-BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 24 hours | -2.0 score on a scale | Standard Deviation 2.2 |
| Part B-40 Mcg-BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | Day 7 | -2.6 score on a scale | Standard Deviation 3.3 |
| Part B-40 Mcg-BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 30 minutes | -1.3 score on a scale | Standard Deviation 2.8 |
| Part B-40 Mcg-BXCL501 | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | Day 3 | -2.0 score on a scale | Standard Deviation 1.9 |
| Part B-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 4 hours | -2.1 score on a scale | Standard Deviation 2.8 |
| Part B-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | Day 7 | -1.1 score on a scale | Standard Deviation 1.4 |
| Part B-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 2 hours | -1.8 score on a scale | Standard Deviation 2.7 |
| Part B-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | Day 3 | -1.9 score on a scale | Standard Deviation 1.6 |
| Part B-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 30 minutes | -0.7 score on a scale | Standard Deviation 0.9 |
| Part B-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 24 hours | -1.8 score on a scale | Standard Deviation 2.4 |
| Part B-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 1 hour | -1.6 score on a scale | Standard Deviation 2 |
| Part B-Placebo | Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline | 8 hours | -2.3 score on a scale | Standard Deviation 2.7 |
Comparison: Part A 30 mcg BXCL501 v/s Part A-Placebo (30 minutes)p-value: 0.9616Mixed effects model
Comparison: Part A-30 mcg BXCL501 v/s Part A-Placebo (Day 1; 1 hour)p-value: 0.546Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/s Part A-Placebo (2 hours)p-value: 0.0961Mixed effects model
Comparison: Part A-30 mcg BXCL501 v/s Part A-Placebo (4 hours)p-value: 0.1359Mixed effects model
Comparison: Part A-30 mcg BXCL501 v/s Part A-Placebo (8 hours)p-value: 0.1688Mixed effects model
Comparison: Part A-30 mcg BXCL501 v/s Part A-Placebo (24 hours)p-value: 0.667Mixed effects model
Comparison: Part A-30 mcg BXCL501 v/s Part A-Placebo (Day 3)p-value: 0.8695Mixed effects model
Comparison: Part A-30 mcg BXCL501 v/s Part A-Placebo (Day 7)p-value: 0.5002Mixed effects model
Comparison: Part A-60 mcg BXCL501 v/s Part A-Placebo (30 minutes)p-value: 0.5631Mixed effects model
Comparison: Part A-60 mcg BXCL501 v/s Part A-Placebo (1 hour)p-value: 0.0089Mixed effects model
Comparison: Part A-60 mcg BXCL501 v/s Part A-Placebo (2 hours)p-value: <0.0001Mixed effects model
Comparison: Part A-60 mcg BXCL501 v/s Part A-Placebo (4 hours)p-value: 0.0011Mixed effects model
Comparison: Part A-60 mcg BXCL501 v/s Part A-Placebo (8 hours)p-value: 0.0008Mixed effects model
Comparison: Part A-60 mcg BXCL501 v/s Part A-Placebo (24 hours)p-value: 0.2847Mixed effects model
Comparison: Part A-60 mcg BXCL501 v/s Part A-Placebo (Day 3)p-value: 0.2616Mixed effects model
Comparison: Part A-60 mcg BXCL501 v/s Part A-Placebo (Day 7)p-value: 0.1989Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (30 minutes)p-value: 0.4585Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (1 hour)p-value: 0.0005Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (2 hours)p-value: 0.0004Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (4 hours)p-value: 0.0025Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (8 hours)p-value: 0.1027Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (24 hours)p-value: 0.7953Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 3)p-value: 0.1416Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 7)p-value: 0.0658Mixed effects model
Secondary
Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline
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.
Time frame: Baseline and 1 hour, 2 hours, 4 hours, 8 hours post-dose
Population: The Intent to Treat Population consisted of all patients in the Safety Population who have a baseline and at least one post-baseline efficacy assessment. Here, number analyzed in each row signifies only the patients with available data that were analyzed for change in ACES score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-30 mcg BXCL501 | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 4 hours | 1.3 score on a scale | Standard Deviation 1 |
| Part A-30 mcg BXCL501 | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 8 hours | 1.4 score on a scale | Standard Deviation 1.1 |
| Part A-30 mcg BXCL501 | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 1 hour | 0.6 score on a scale | Standard Deviation 0.6 |
| Part A-30 mcg BXCL501 | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 2 hours | 0.9 score on a scale | Standard Deviation 1 |
| Part A-60 mcg BXCL501 | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 4 hours | 2.7 score on a scale | Standard Deviation 1.2 |
| Part A-60 mcg BXCL501 | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 2 hours | 2.7 score on a scale | Standard Deviation 1.6 |
| Part A-60 mcg BXCL501 | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 8 hours | 2.2 score on a scale | Standard Deviation 0.9 |
| Part A-60 mcg BXCL501 | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 1 hour | 1.1 score on a scale | Standard Deviation 0.7 |
| Part A-Placebo | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 2 hours | 0.9 score on a scale | Standard Deviation 0.9 |
| Part A-Placebo | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 8 hours | 0.9 score on a scale | Standard Deviation 0.8 |
| Part A-Placebo | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 1 hour | 0.5 score on a scale | Standard Deviation 0.5 |
| Part A-Placebo | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 4 hours | 0.9 score on a scale | Standard Deviation 1.1 |
| Part B-40 Mcg-BXCL501 | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 4 hours | 2.4 score on a scale | Standard Deviation 2 |
| Part B-40 Mcg-BXCL501 | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 8 hours | 1.5 score on a scale | Standard Deviation 1.5 |
| Part B-40 Mcg-BXCL501 | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 2 hours | 2.5 score on a scale | Standard Deviation 1.9 |
| Part B-40 Mcg-BXCL501 | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 1 hour | 1.8 score on a scale | Standard Deviation 1.6 |
| Part B-Placebo | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 2 hours | 0.7 score on a scale | Standard Deviation 1.3 |
| Part B-Placebo | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 1 hour | 0.4 score on a scale | Standard Deviation 0.8 |
| Part B-Placebo | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 8 hours | 1.0 score on a scale | Standard Deviation 1.2 |
| Part B-Placebo | Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline | 4 hours | 1.0 score on a scale | Standard Deviation 1.4 |
Comparison: Part A -30 mcg BXCL501 v/s Part A-Placebo (Day 1; 1 hour)p-value: 0.876Mixed effects model
Comparison: Part A 30 mcg BXCL501 v/s Part A-Placebo (Day 1; 2 hours)p-value: 0.9077Mixed effects model
Comparison: Part A 30 mcg BXCL501 vs Part A-Placebo (Day1; 4 hours)p-value: 0.7208Mixed effects model
Comparison: Part A BXCL501 30 mcg v/s Part A-Placebo(Day 1;8 hours)p-value: 0.3666Mixed effects model
Comparison: Part A BXCL501 60 mcg v/s Placebo-Part A (Day1; 1 hour)p-value: 0.0191Mixed effects model
Comparison: Part A BXCL501 60 mcg v/s Part A-Placebo (Day 1; 2 hours)p-value: 0.0006Mixed effects model
Comparison: Part A-60 mcg BXCL501 v/s Part A-Placebo (Day 1; 4 hours)p-value: <0.0001Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1;8 hours)p-value: 0.0003Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 1 hour)p-value: 0.0006Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 2 hours)p-value: 0.0002Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 4 hours)p-value: 0.0029Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 8 hours)p-value: 0.2446Mixed effects model
Secondary
Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline
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.
Time frame: Baseline and at 30 minutes, 1 hour, 4 hours, 8 hours, 24 hours, Day 3 and Day 7 post-dose
Population: The Intent to Treat Population consisted of all patients in the Safety Population who have a baseline and at least one post-baseline efficacy assessment. Here, number analyzed in each row signifies only the patients with available data that were analyzed for change in PEC score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-30 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 30 minutes | -2.2 score on a scale | Standard Deviation 1.6 |
| Part A-30 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 7 | -4.9 score on a scale | Standard Deviation 3.9 |
| Part A-30 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 3 | -5.3 score on a scale | Standard Deviation 5 |
| Part A-30 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 4 hours | -6.8 score on a scale | Standard Deviation 4.4 |
| Part A-30 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 1 hours | -3.6 score on a scale | Standard Deviation 1.9 |
| Part A-30 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 8 hours | -7.1 score on a scale | Standard Deviation 4.6 |
| Part A-30 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 2; 24 hours | -5.7 score on a scale | Standard Deviation 4 |
| Part A-60 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 2; 24 hours | -6.0 score on a scale | Standard Deviation 3.8 |
| Part A-60 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 8 hours | -8.8 score on a scale | Standard Deviation 3.1 |
| Part A-60 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 1 hours | -5.4 score on a scale | Standard Deviation 3.6 |
| Part A-60 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 30 minutes | -1.7 score on a scale | Standard Deviation 2.2 |
| Part A-60 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 3 | -5.9 score on a scale | Standard Deviation 4.2 |
| Part A-60 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 4 hours | -8.1 score on a scale | Standard Deviation 2.5 |
| Part A-60 mcg BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 7 | -4.6 score on a scale | Standard Deviation 3.9 |
| Part A-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 8 hours | -4.6 score on a scale | Standard Deviation 3.3 |
| Part A-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 30 minutes | -0.6 score on a scale | Standard Deviation 1.4 |
| Part A-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 1 hours | -2.3 score on a scale | Standard Deviation 2 |
| Part A-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 4 hours | -4.1 score on a scale | Standard Deviation 3.6 |
| Part A-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 2; 24 hours | -4.3 score on a scale | Standard Deviation 3.3 |
| Part A-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 3 | -3.9 score on a scale | Standard Deviation 3.7 |
| Part A-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 7 | -3.4 score on a scale | Standard Deviation 4.4 |
| Part B-40 Mcg-BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 4 hours | -6.5 score on a scale | Standard Deviation 4.5 |
| Part B-40 Mcg-BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 2; 24 hours | -3.4 score on a scale | Standard Deviation 3.7 |
| Part B-40 Mcg-BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 1 hours | -5.7 score on a scale | Standard Deviation 4.4 |
| Part B-40 Mcg-BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 7 | -2.5 score on a scale | Standard Deviation 4.1 |
| Part B-40 Mcg-BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 3 | -3.2 score on a scale | Standard Deviation 3.3 |
| Part B-40 Mcg-BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 30 minutes | -1.0 score on a scale | Standard Deviation 2.4 |
| Part B-40 Mcg-BXCL501 | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 8 hours | -5.0 score on a scale | Standard Deviation 4.3 |
| Part B-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 4 hours | -2.8 score on a scale | Standard Deviation 4.8 |
| Part B-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 7 | -1.5 score on a scale | Standard Deviation 1.5 |
| Part B-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 3 | -1.8 score on a scale | Standard Deviation 2.7 |
| Part B-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | Day 2; 24 hours | -2.4 score on a scale | Standard Deviation 4 |
| Part B-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 1 hours | -1.9 score on a scale | Standard Deviation 3.2 |
| Part B-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 30 minutes | -1.0 score on a scale | Standard Deviation 1.7 |
| Part B-Placebo | Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline | 8 hours | -3.2 score on a scale | Standard Deviation 4.7 |
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 1; 30 minutes)p-value: 0.0926Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 1; 1 hour)p-value: 0.3976Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 1; 4 hours)p-value: 0.1169Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 1; 8 hours)p-value: 0.3786Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 2; 24hours)p-value: 0.564Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 3)p-value: 0.602Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 7)p-value: 0.5875Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 30 minutes)p-value: 0.1055Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 1 hour)p-value: 0.0024Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 4 hours)p-value: 0.0016Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 8 hours)p-value: 0.0002Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 2; 24 hours)p-value: 0.2039Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 3)p-value: 0.1948Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 7)p-value: 0.5615Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 30 minutes)p-value: 0.8266Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 1 hour)p-value: 0.0002Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 4 hours)p-value: 0.0004Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 8 hours)p-value: 0.1037Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 2; 24 hours)p-value: 0.3267Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 3)p-value: 0.0339Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day7)p-value: 0.1892Mixed effects model
Secondary
Clinical Global Impression - Improvement (CGI-I) Agitation Score
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.
Time frame: 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours post-dose
Population: The Intent to Treat Population consisted of all patients in the Safety Population who have a baseline and at least one post-baseline efficacy assessment. Here, number analyzed in each row signifies only the patients with available data that were analyzed for CGI-I agitation score.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-30 mcg BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 4 hours | 2.4 score on a scale | Standard Error 0.3 |
| Part A-30 mcg BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 30 minutes | 3.3 score on a scale | Standard Error 0.2 |
| Part A-30 mcg BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 8 hours | 2.3 score on a scale | Standard Error 0.2 |
| Part A-30 mcg BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 1 hour | 3.0 score on a scale | Standard Error 0.2 |
| Part A-30 mcg BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 2 hours | 2.4 score on a scale | Standard Error 0.2 |
| Part A-60 mcg BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 4 hours | 1.5 score on a scale | Standard Error 0.2 |
| Part A-60 mcg BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 2 hours | 1.6 score on a scale | Standard Error 0.2 |
| Part A-60 mcg BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 1 hour | 2.6 score on a scale | Standard Error 0.2 |
| Part A-60 mcg BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 8 hours | 1.4 score on a scale | Standard Error 0.2 |
| Part A-60 mcg BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 30 minutes | 3.4 score on a scale | Standard Error 0.2 |
| Part A-Placebo | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 2 hours | 3.2 score on a scale | Standard Error 0.2 |
| Part A-Placebo | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 30 minutes | 3.5 score on a scale | Standard Error 0.2 |
| Part A-Placebo | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 1 hour | 3.3 score on a scale | Standard Error 0.2 |
| Part A-Placebo | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 4 hours | 3.0 score on a scale | Standard Error 0.3 |
| Part A-Placebo | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 8 hours | 3.0 score on a scale | Standard Error 0.2 |
| Part B-40 Mcg-BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 8 hours | 2.5 score on a scale | Standard Error 0.3 |
| Part B-40 Mcg-BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 30 minutes | 3.5 score on a scale | Standard Error 0.1 |
| Part B-40 Mcg-BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 4 hours | 2.0 score on a scale | Standard Error 0.3 |
| Part B-40 Mcg-BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 2 hours | 1.9 score on a scale | Standard Error 0.2 |
| Part B-40 Mcg-BXCL501 | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 1 hour | 2.5 score on a scale | Standard Error 0.2 |
| Part B-Placebo | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 2 hours | 3.6 score on a scale | Standard Error 0.2 |
| Part B-Placebo | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 4 hours | 3.3 score on a scale | Standard Error 0.3 |
| Part B-Placebo | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 30 minutes | 3.7 score on a scale | Standard Error 0.1 |
| Part B-Placebo | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 8 hours | 3.5 score on a scale | Standard Error 0.3 |
| Part B-Placebo | Clinical Global Impression - Improvement (CGI-I) Agitation Score | 1 hour | 3.5 score on a scale | Standard Error 0.2 |
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 1; 30 minutes)p-value: 0.408Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 1; 1 hour)p-value: 0.4198Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day1; 2 hours)p-value: 0.037Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 1; 4 hours)p-value: 0.1324Mixed effects model
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 1; 8 hours)p-value: 0.0624Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 30 minutes)p-value: 0.6334Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 1 hour)p-value: 0.0275Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 2 hours)p-value: <0.0001Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 4 hours)p-value: 0.0001Mixed effects model
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (Day1; 8 hours)p-value: <0.0001Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 30 minutes)p-value: 0.2806Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 1 hour)p-value: 0.0002Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 2 hour)p-value: <0.0001Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 4 hours)p-value: 0.0009Mixed effects model
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 8 hours)p-value: 0.0081Mixed effects model
Secondary
Number of Patients at Each Dose Who Achieve a 40% Reduction From Baseline in PEC Total Score at 2 Hours Post-dose (Responders)
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.
Time frame: Baseline and 2 hours post-dose
Population: The Intent to Treat Population consisted of all patients in the Safety Population who have a baseline and at least one post-baseline efficacy assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A-30 mcg BXCL501 | Number of Patients at Each Dose Who Achieve a 40% Reduction From Baseline in PEC Total Score at 2 Hours Post-dose (Responders) | 4 Participants |
| Part A-60 mcg BXCL501 | Number of Patients at Each Dose Who Achieve a 40% Reduction From Baseline in PEC Total Score at 2 Hours Post-dose (Responders) | 14 Participants |
| Part A-Placebo | Number of Patients at Each Dose Who Achieve a 40% Reduction From Baseline in PEC Total Score at 2 Hours Post-dose (Responders) | 1 Participants |
| Part B-40 Mcg-BXCL501 | Number of Patients at Each Dose Who Achieve a 40% Reduction From Baseline in PEC Total Score at 2 Hours Post-dose (Responders) | 9 Participants |
| Part B-Placebo | Number of Patients at Each Dose Who Achieve a 40% Reduction From Baseline in PEC Total Score at 2 Hours Post-dose (Responders) | 2 Participants |
Comparison: Part A-30 mcg BXCL501 V/S Part A-Placebo (2 hours post administration)p-value: 0.3359Fisher Exact
Comparison: Part A-60 mcg BXCL501 V/S Part A-Placebo (2 hours post administration)p-value: 0.0004Fisher Exact
p-value: 0.0351Fisher Exact
Secondary
Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion
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.
Time frame: At 30 minutes, 2 hours, 4 hours, 24 hours post dose
Population: The safety population consisted of all patients who received study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-30 mcg BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 30 minutes Post dose | 0 Participants |
| Part A-30 mcg BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 2 hours post dose | 0 Participants |
| Part A-30 mcg BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 4 hours post dose | 0 Participants |
| Part A-30 mcg BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 24 hours post dose | 0 Participants |
| Part A-60 mcg BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 4 hours post dose | 0 Participants |
| Part A-60 mcg BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 2 hours post dose | 0 Participants |
| Part A-60 mcg BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 30 minutes Post dose | 0 Participants |
| Part A-60 mcg BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 24 hours post dose | 0 Participants |
| Part A-90 mcg BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 24 hours post dose | 0 Participants |
| Part A-90 mcg BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 4 hours post dose | 0 Participants |
| Part A-90 mcg BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 2 hours post dose | 0 Participants |
| Part A-90 mcg BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 30 minutes Post dose | 0 Participants |
| Part A-Placebo | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 30 minutes Post dose | 0 Participants |
| Part A-Placebo | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 24 hours post dose | 0 Participants |
| Part A-Placebo | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 2 hours post dose | 0 Participants |
| Part A-Placebo | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 4 hours post dose | 0 Participants |
| Part B-40 Mcg-BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 4 hours post dose | 0 Participants |
| Part B-40 Mcg-BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 24 hours post dose | 0 Participants |
| Part B-40 Mcg-BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 2 hours post dose | 0 Participants |
| Part B-40 Mcg-BXCL501 | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 30 minutes Post dose | 0 Participants |
| Part B-Placebo | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 2 hours post dose | 0 Participants |
| Part B-Placebo | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 4 hours post dose | 0 Participants |
| Part B-Placebo | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 24 hours post dose | 0 Participants |
| Part B-Placebo | Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion | 30 minutes Post dose | 0 Participants |
Secondary
Number of Patients With Event Time Taken for Medication to Dissolve
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.
Time frame: At 30 minutes post-dose
Population: The safety population consisted of all patients who received study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-30 mcg BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 1- 30 seconds | 0 Participants |
| Part A-30 mcg BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 31- 59 seconds | 0 Participants |
| Part A-30 mcg BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 1- 2 minutes | 10 Participants |
| Part A-30 mcg BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 3+ minutes | 6 Participants |
| Part A-60 mcg BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 1- 2 minutes | 8 Participants |
| Part A-60 mcg BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 31- 59 seconds | 0 Participants |
| Part A-60 mcg BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 1- 30 seconds | 0 Participants |
| Part A-60 mcg BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 3+ minutes | 12 Participants |
| Part A-90 mcg BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 3+ minutes | 2 Participants |
| Part A-90 mcg BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 1- 2 minutes | 2 Participants |
| Part A-90 mcg BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 31- 59 seconds | 0 Participants |
| Part A-90 mcg BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 1- 30 seconds | 0 Participants |
| Part A-Placebo | Number of Patients With Event Time Taken for Medication to Dissolve | 1- 30 seconds | 0 Participants |
| Part A-Placebo | Number of Patients With Event Time Taken for Medication to Dissolve | 3+ minutes | 6 Participants |
| Part A-Placebo | Number of Patients With Event Time Taken for Medication to Dissolve | 31- 59 seconds | 0 Participants |
| Part A-Placebo | Number of Patients With Event Time Taken for Medication to Dissolve | 1- 2 minutes | 8 Participants |
| Part B-40 Mcg-BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 1- 2 minutes | 12 Participants |
| Part B-40 Mcg-BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 3+ minutes | 11 Participants |
| Part B-40 Mcg-BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 31- 59 seconds | 0 Participants |
| Part B-40 Mcg-BXCL501 | Number of Patients With Event Time Taken for Medication to Dissolve | 1- 30 seconds | 0 Participants |
| Part B-Placebo | Number of Patients With Event Time Taken for Medication to Dissolve | 31- 59 seconds | 2 Participants |
| Part B-Placebo | Number of Patients With Event Time Taken for Medication to Dissolve | 1- 2 minutes | 10 Participants |
| Part B-Placebo | Number of Patients With Event Time Taken for Medication to Dissolve | 3+ minutes | 11 Participants |
| Part B-Placebo | Number of Patients With Event Time Taken for Medication to Dissolve | 1- 30 seconds | 0 Participants |
Secondary
Part B: Change From Baseline in the Total Score of 3 Supplementary Items of Positive and Negative Syndrome Scale (PANSS)
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.
Time frame: Baseline and at 2 hours post-dose
Population: The Intent to Treat Population consisted of all patients in the Safety Population who have a baseline and at least one post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A-30 mcg BXCL501 | Part B: Change From Baseline in the Total Score of 3 Supplementary Items of Positive and Negative Syndrome Scale (PANSS) | -3.7 score on a scale | Standard Deviation 2.9 |
| Part A-60 mcg BXCL501 | Part B: Change From Baseline in the Total Score of 3 Supplementary Items of Positive and Negative Syndrome Scale (PANSS) | -0.6 score on a scale | Standard Deviation 2.3 |
Comparison: Part B-40 mcg-BXCL501 v/s Part B-Placebo (2 hours post administration)p-value: 0.0002Mixed effects model