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| Name | Class |
|---|---|
| Cognitive Research Corporation | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1- 30 Micrograms | Active Comparator | Cohort 1 consists of 10 patients out of whom 8 patients receive 30 Micrograms film and the remaining 2 patients receive a placebo |
|
| Cohort 2- 60 Micrograms | Active Comparator | Cohort 2 consists of 10 patients out of whom 8 patients receive 60 Micrograms film and the remaining 2 patients receive a placebo. Additional 20 subjects receive 60 Micrograms or placebo. |
|
| Cohort 3- 90 Micrograms | Active Comparator | Cohort 3 consists of 10 patients out of whom 8 patients receive 90 Micrograms film and the remaining 2 patients receive a placebo |
|
| Part B Cohort | Active Comparator | Part B cohort consists 46 subjects receiving 40 Micrograms or placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sublingual film containing Dexmedetomidine | Drug | Sublingual film containing Dexmedetomidine |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and 2 hours post-dose |
| 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. | Day 7 post dose |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert Risinger, MD | BioXcel Therapeutics | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| BioXcel Clinical Research Site | Homestead | Florida | 33032 | United States | ||
| BioXcel Clinical Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36280451 | Derived | Persson NDA, Uusalo P, Nedergaard M, Lohela TJ, Lilius TO. Could dexmedetomidine be repurposed as a glymphatic enhancer? Trends Pharmacol Sci. 2022 Dec;43(12):1030-1040. doi: 10.1016/j.tips.2022.09.007. Epub 2022 Oct 21. |
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All the assessments were performed as per the schedule of the assessments.
The trial was conducted at 4 sites in the United States from 27 December 2019 to 24 January 2022.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A-30 mcg BXCL501 | Randomized patients self-administered 30 micrograms (mcg) of BXCL501 sublingually under the supervision of a trained staff member. |
| FG001 | Part A-60 mcg BXCL501 | Randomized patients self-administered 60 mcg BXCL501 sublingually under the supervision of a trained staff member. |
| FG002 | Part A- 90 mcg BXCL501 | Randomized patients self-administered 90 mcg BXCL501 sublingually under the supervision of a trained staff member. |
| FG003 | Part A-Placebo | Randomized patients self-administered Placebo sublingually under the supervision of a trained staff member. |
| FG004 | Part B-40 Mcg-BXCL501 | Randomized patients self-administered 40 mcg BXCL501 sublingually under the supervision of a trained staff member. |
| FG005 | Part B-Placebo | Randomized patients self-administered Placebo sublingually under the supervision of a trained staff member. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The safety population consisted of all patients who received study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A-30 mcg BXCL501 | Randomized patients self-administered 30 mcg of BXCL501 sublingually under the supervision of a trained staff member. |
| BG001 | Part A-60 mcg BXCL501 | Randomized patients self-administered 60 mcg BXCL501 sublingually under the supervision of a trained staff member. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline and 2 hours post-dose |
|
Day 7 post-dose
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A-30 mcg BXCL501 | Randomized patients self-administered 30 mcg of BXCL501 sublingually under the supervision of a trained staff member. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sepsis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Somnolence | Nervous system disorders | MedDRA (24.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| SVP Clinical and Medical Affairs | BioXcel Therapeutics | (203) 530-5000 | DKostic@bioxceltherapeutics.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 4, 2021 | Aug 1, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 28, 2020 | Jul 27, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D011595 | Psychomotor Agitation |
| D003704 | Dementia |
| ID | Term |
|---|---|
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D011596 | Psychomotor Disorders |
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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
|
| Sublingual Placebo Film | Drug | Sublingual placebo film that matches BXCL501 |
|
| Baseline and at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, Day 3, Day 7 post-dose |
| 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. | Baseline and 1 hour, 2 hours, 4 hours, 8 hours post-dose |
| 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. | Baseline and at 30 minutes, 1 hour, 4 hours, 8 hours, 24 hours, Day 3 and Day 7 post-dose |
| 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. | Baseline and 2 hours post-dose |
| 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. | Baseline and at 2 hours, and 24 hours post-dose |
| 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. | 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours post-dose |
| 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. | Baseline and at 2 Hours and Day 7 post-dose |
| 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. | At 30 minutes post-dose |
| 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. | At 30 minutes, 2 hours, 4 hours, 24 hours post dose |
| 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. | Baseline and at 2 hours post-dose |
| Miami Lakes |
| Florida |
| 33016 |
| United States |
| BioXcel Clinical Research Site | Springfield | Massachusetts | 01103 | United States |
| BioXcel Clinical Research Site | Caro | Michigan | 48723 | United States |
| BioXcel Clinical Research Site | Toms River | New Jersey | 08755 | United States |
| Assisted living facility was closed |
|
| BG002 | Part A- 90 mcg BXCL501 | Randomized patients self-administered 90 mcg BXCL501 sublingually under the supervision of a trained staff member. |
| BG003 | Part A-Placebo | Randomized patients self-administered Placebo sublingually under the supervision of a trained staff member. |
| BG004 | Part B-40 Mcg-BXCL501 | Randomized patients self-administered 40 mcg BXCL501 sublingually under the supervision of a trained staff member. |
| BG005 | Part B-Placebo | Randomized patients self-administered Placebo sublingually under the supervision of a trained staff member. |
| BG006 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Part A-60 mcg BXCL501 | Randomized patients self-administered 60 mcg BXCL501 sublingually under the supervision of a trained staff member. |
| OG002 | Part A-90 mcg BXCL501 | Randomized patients self-administered 90 mcg BXCL501 sublingually under the supervision of a trained staff member. |
| OG003 | Part A-Placebo | Randomized patients self-administered Placebo sublingually under the supervision of a trained staff member. |
| OG004 | Part B-40 Mcg-BXCL501 | Randomized patients self-administered 40 mcg BXCL501 sublingually under the supervision of a trained staff member. |
| OG005 | Part B-Placebo | Randomized patients self-administered Placebo sublingually under the supervision of a trained staff member. |
|
|
|
| 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. | The safety population consisted of all patients who received study drug. | Posted | Count of Participants | Participants | Day 7 post dose |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline and at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, Day 3, Day 7 post-dose |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline and 1 hour, 2 hours, 4 hours, 8 hours post-dose |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline and at 30 minutes, 1 hour, 4 hours, 8 hours, 24 hours, Day 3 and Day 7 post-dose |
|
|
|
|
| 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. | 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. | Posted | Count of Participants | Participants | Baseline and 2 hours post-dose |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline and at 2 hours, and 24 hours post-dose |
|
|
|
|
| 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. | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours post-dose |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline and at 2 Hours and Day 7 post-dose |
|
|
|
|
| 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. | The safety population consisted of all patients who received study drug. | Posted | Count of Participants | Participants | At 30 minutes post-dose |
|
|
|
| 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. | The safety population consisted of all patients who received study drug. | Posted | Count of Participants | Participants | At 30 minutes, 2 hours, 4 hours, 24 hours post dose |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline and at 2 hours post-dose |
|
|
|
|
| 0 |
| 16 |
| 0 |
| 16 |
| 11 |
| 16 |
| EG001 | Part A-60 mcg BXCL501 | Randomized patients self-administered 60 mcg BXCL501 sublingually under the supervision of a trained staff member. | 0 | 20 | 0 | 20 | 14 | 20 |
| EG002 | Part A- 90 mcg BXCL501 | Randomized patients self-administered 90 mcg BXCL501 sublingually under the supervision of a trained staff member. | 0 | 4 | 0 | 4 | 4 | 4 |
| EG003 | Part A-Placebo | Randomized patients self-administered Placebo sublingually under the supervision of a trained staff member. | 0 | 14 | 0 | 14 | 0 | 14 |
| EG004 | Part B-40 Mcg-BXCL501 | Randomized patients self-administered 40 mcg BXCL501 sublingually under the supervision of a trained staff member. | 1 | 23 | 1 | 23 | 12 | 23 |
| EG005 | Part B-Placebo | Randomized patients self-administered Placebo sublingually under the supervision of a trained staff member. | 0 | 23 | 0 | 23 | 2 | 23 |
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (24.0) | Non-systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA (24.0) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (24.0) | Non-systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA (24.0) | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (24.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (24.0) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (24.0) | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (24.0) | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (24.0) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (24.0) | Non-systematic Assessment |
|
Not provided
Not provided
| D019954 |
| Neurobehavioral Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000096762 | Aberrant Motor Behavior in Dementia |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| 1 hour |
|
| 2 hours |
|
| 4 hours |
|
| 8 hours |
|
| 24 hours |
|
| Day 3 |
|
| Day 7 |
|
| 0.5460 |
| Superiority |
| Part A-30 mcg BXCL501 V/s Part A-Placebo (2 hours) | Mixed effects model | 0.0961 | Superiority |
| Part A-30 mcg BXCL501 v/s Part A-Placebo (4 hours) | Mixed effects model | 0.1359 | Superiority |
| Part A-30 mcg BXCL501 v/s Part A-Placebo (8 hours) | Mixed effects model | 0.1688 | Superiority |
| Part A-30 mcg BXCL501 v/s Part A-Placebo (24 hours) | Mixed effects model | 0.6670 | Superiority |
| Part A-30 mcg BXCL501 v/s Part A-Placebo (Day 3) | Mixed effects model | 0.8695 | Superiority |
| Part A-30 mcg BXCL501 v/s Part A-Placebo (Day 7) | Mixed effects model | 0.5002 | Superiority |
| Part A-60 mcg BXCL501 v/s Part A-Placebo (30 minutes) | Mixed effects model | 0.5631 | Superiority |
| Part A-60 mcg BXCL501 v/s Part A-Placebo (1 hour) | Mixed effects model | 0.0089 | Superiority |
| Part A-60 mcg BXCL501 v/s Part A-Placebo (2 hours) | Mixed effects model | <.0001 | Superiority |
| Part A-60 mcg BXCL501 v/s Part A-Placebo (4 hours) | Mixed effects model | 0.0011 | Superiority |
| Part A-60 mcg BXCL501 v/s Part A-Placebo (8 hours) | Mixed effects model | 0.0008 | Superiority |
| Part A-60 mcg BXCL501 v/s Part A-Placebo (24 hours) | Mixed effects model | 0.2847 | Superiority |
| Part A-60 mcg BXCL501 v/s Part A-Placebo (Day 3) | Mixed effects model | 0.2616 | Superiority |
| Part A-60 mcg BXCL501 v/s Part A-Placebo (Day 7) | Mixed effects model | 0.1989 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (30 minutes) | Mixed effects model | 0.4585 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (1 hour) | Mixed effects model | 0.0005 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (2 hours) | Mixed effects model | 0.0004 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (4 hours) | Mixed effects model | 0.0025 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (8 hours) | Mixed effects model | 0.1027 | 2-Sided | 95 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (24 hours) | Mixed effects model | 0.7953 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 3) | Mixed effects model | 0.1416 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 7) | Mixed effects model | 0.0658 | Superiority |
|
| 2 hours |
|
|
| 4 hours |
|
|
| 8 hours |
|
|
| 0.9077 |
| Superiority |
| Part A 30 mcg BXCL501 vs Part A-Placebo (Day1; 4 hours) | Mixed effects model | 0.7208 | Superiority |
| Part A BXCL501 30 mcg v/s Part A-Placebo(Day 1;8 hours) | Mixed effects model | 0.3666 | Superiority |
| Part A BXCL501 60 mcg v/s Placebo-Part A (Day1; 1 hour) | Mixed effects model | 0.0191 | Superiority |
| Part A BXCL501 60 mcg v/s Part A-Placebo (Day 1; 2 hours) | Mixed effects model | 0.0006 | Superiority |
| Part A-60 mcg BXCL501 v/s Part A-Placebo (Day 1; 4 hours) | Mixed effects model | <.0001 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1;8 hours) | Mixed effects model | 0.0003 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 1 hour) | Mixed effects model | 0.0006 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 2 hours) | Mixed effects model | 0.0002 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 4 hours) | Mixed effects model | 0.0029 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 8 hours) | Mixed effects model | 0.2446 | Superiority |
|
| 1 hours |
|
|
| 4 hours |
|
|
| 8 hours |
|
|
| Day 2; 24 hours |
|
|
| Day 3 |
|
|
| Day 7 |
|
|
| 0.3976 |
| Superiority |
| Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 1; 4 hours) | Mixed effects model | 0.1169 | Superiority |
| Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 1; 8 hours) | Mixed effects model | 0.3786 | Superiority |
| Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 2; 24hours) | Mixed effects model | 0.5640 | Superiority |
| Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 3) | Mixed effects model | 0.6020 | Superiority |
| Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 7) | Mixed effects model | 0.5875 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 30 minutes) | Mixed effects model | 0.1055 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 1 hour) | Mixed effects model | 0.0024 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 4 hours) | Mixed effects model | 0.0016 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 8 hours) | Mixed effects model | 0.0002 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 2; 24 hours) | Mixed effects model | 0.2039 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 3) | Mixed effects model | 0.1948 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 7) | Mixed effects model | 0.5615 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 30 minutes) | Mixed effects model | 0.8266 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 1 hour) | Mixed effects model | 0.0002 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 4 hours) | Mixed effects model | 0.0004 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 8 hours) | Mixed effects model | 0.1037 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 2; 24 hours) | Mixed effects model | 0.3267 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 3) | Mixed effects model | 0.0339 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day7) | Mixed effects model | 0.1892 | Superiority |
| 0.0004 |
| Superiority |
| Fisher Exact | 0.0351 | Superiority |
| 24 hours |
|
| 0.8977 |
| Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 2 hours) | Mixed effects model | 0.0002 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 2; 24 hours) | Mixed effects model | 0.3147 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 2 hours) | Mixed effects model | <.0001 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 2; 24 hours) | Mixed effects model | 0.1241 | Superiority |
|
| 1 hour |
|
|
| 2 hours |
|
|
| 4 hours |
|
|
| 8 hours |
|
|
| 0.4198 |
| Superiority |
| Part A-30 mcg BXCL501 V/S Part A-Placebo (Day1; 2 hours) | Mixed effects model | 0.0370 | Superiority |
| Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 1; 4 hours) | Mixed effects model | 0.1324 | Superiority |
| Part A-30 mcg BXCL501 V/S Part A-Placebo (Day 1; 8 hours) | Mixed effects model | 0.0624 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 30 minutes) | Mixed effects model | 0.6334 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 1 hour) | Mixed effects model | 0.0275 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 2 hours) | Mixed effects model | <.0001 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 4 hours) | Mixed effects model | 0.0001 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day1; 8 hours) | Mixed effects model | <.0001 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 30 minutes) | Mixed effects model | 0.2806 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 1 hour) | Mixed effects model | 0.0002 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 2 hour) | Mixed effects model | <.0001 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 4 hours) | Mixed effects model | 0.0009 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 8 hours) | Mixed effects model | 0.0081 | Superiority |
| Day 7 |
|
| 0.0966 |
| Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 1; 2 hours) | Mixed effects model | <.0001 | Superiority |
| Part A-60 mcg BXCL501 V/S Part A-Placebo (Day 7) | Mixed effects model | 0.0290 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 1; 2 hours) | Mixed effects model | 0.0937 | Superiority |
| Part B-40 mcg-BXCL501 v/s Part B-Placebo (Day 7) | Mixed effects model | 0.2747 | Superiority |
| 31- 59 seconds |
|
| 1- 2 minutes |
|
| 3+ minutes |
|
| 2 hours post dose |
|
| 4 hours post dose |
|
| 24 hours post dose |
|