NCT04251910: TRANQUILITY

Sub-Lingual Dexmedetomidine in Agitation Associated With Dementia

Completed Phase 1, PHASE2 Results posted Last updated 21 September 2023

What this trial tests

Phase 1, PHASE2 trial testing Sublingual film containing Dexmedetomidine in Agitation,Psychomotor in 100 participants. Completed in 24 January 2022.

Timeline

27 December 2019

Primary endpoint
24 January 2022

24 January 2022

Quick facts

Lead sponsor	BioXcel Therapeutics Inc
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	100
Start date	27 December 2019
Primary completion	24 January 2022
Estimated completion	24 January 2022
Sites	5 locations across United States

Drugs / interventions tested

• Sublingual film containing Dexmedetomidine — full drug profile →
• Sublingual Placebo Film — full drug profile →

Conditions studied

• Agitation,Psychomotor — all drugs for Agitation,Psychomotor →
• Dementia — all drugs for Dementia →

Sponsor

BioXcel Therapeutics Inc — full company profile →

Who can join

65 and older, any sex, with Agitation,Psychomotor or Dementia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Change From Baseline in Positive and Negative Syndrome Scale-Excited Component (PEC) Total Score Primary · 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.

Group	Value	95% CI
Part A-30 mcg BXCL501	-5.4	± 3.4
Part A-60 mcg BXCL501	-7.1	± 3.8
Part A-Placebo	-2.9	± 2.7
Part B-40 Mcg-BXCL501	-6.8	± 5.1
Part B-Placebo	-1.8	± 4.4

Number of Patients With Adverse Events Primary · Day 7 post dose

The safety and tolerability of single doses of BXCL501 was determined in treatment of acute agitation associated with dementia.

Group	Value	95% CI
Part A-30 mcg BXCL501	11
Part A-60 mcg BXCL501	14
Part A- 90 mcg BXCL501	4
Part A-Placebo	0
Part B-40 Mcg-BXCL501	12
Part B-Placebo	2

Change in Pittsburgh Agitation Scale (PAS) Total Score From Baseline Secondary · 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 o

30 minutes

Group	Value	95% CI
Part A-30 mcg BXCL501	-1.3	± 1.2
Part A-60 mcg BXCL501	-1.6	± 1.7
Part A-Placebo	-1.3	± 1.6
Part B-40 Mcg-BXCL501	-1.3	± 2.8
Part B-Placebo	-0.7	± 0.9

1 hour

Group	Value	95% CI
Part A-30 mcg BXCL501	-2.5	± 1.8
Part A-60 mcg BXCL501	-4.0	± 2.2
Part A-Placebo	-2.1	± 1.8
Part B-40 Mcg-BXCL501	-4.7	± 3.2
Part B-Placebo	-1.6	± 2.0

2 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	-3.9	± 2.4
Part A-60 mcg BXCL501	-5.8	± 2.1
Part A-Placebo	-2.6	± 2.4
Part B-40 Mcg-BXCL501	-5.4	± 3.4
Part B-Placebo	-1.8	± 2.7

4 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	-4.7	± 3.1
Part A-60 mcg BXCL501	-6.4	± 1.3
Part A-Placebo	-3.3	± 2.8
Part B-40 Mcg-BXCL501	-5.2	± 3.7
Part B-Placebo	-2.1	± 2.8

8 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	-4.4	± 3.2
Part A-60 mcg BXCL501	-6.2	± 1.7
Part A-Placebo	-3.1	± 2.0
Part B-40 Mcg-BXCL501	-4.1	± 3.5
Part B-Placebo	-2.3	± 2.7

24 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	-4.3	± 2.8
Part A-60 mcg BXCL501	-4.9	± 2.1
Part A-Placebo	-3.9	± 2.4
Part B-40 Mcg-BXCL501	-2.0	± 2.2
Part B-Placebo	-1.8	± 2.4

Day 3

Group	Value	95% CI
Part A-30 mcg BXCL501	-3.9	± 3.4
Part A-60 mcg BXCL501	-4.9	± 2.4
Part A-Placebo	-3.7	± 3.4
Part B-40 Mcg-BXCL501	-2.0	± 1.9
Part B-Placebo	-1.9	± 1.6

Day 7

Group	Value	95% CI
Part A-30 mcg BXCL501	-3.9	± 3.1
Part A-60 mcg BXCL501	-4.3	± 2.3
Part A-Placebo	-3.3	± 2.7
Part B-40 Mcg-BXCL501	-2.6	± 3.3
Part B-Placebo	-1.1	± 1.4

Changes in Agitation-Calmness Evaluation Scale (ACES) Score From Baseline Secondary · 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.

1 hour

Group	Value	95% CI
Part A-30 mcg BXCL501	0.6	± 0.6
Part A-60 mcg BXCL501	1.1	± 0.7
Part A-Placebo	0.5	± 0.5
Part B-40 Mcg-BXCL501	1.8	± 1.6
Part B-Placebo	0.4	± 0.8

2 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	0.9	± 1.0
Part A-60 mcg BXCL501	2.7	± 1.6
Part A-Placebo	0.9	± 0.9
Part B-40 Mcg-BXCL501	2.5	± 1.9
Part B-Placebo	0.7	± 1.3

4 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	1.3	± 1.0
Part A-60 mcg BXCL501	2.7	± 1.2
Part A-Placebo	0.9	± 1.1
Part B-40 Mcg-BXCL501	2.4	± 2.0
Part B-Placebo	1.0	± 1.4

8 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	1.4	± 1.1
Part A-60 mcg BXCL501	2.2	± 0.9
Part A-Placebo	0.9	± 0.8
Part B-40 Mcg-BXCL501	1.5	± 1.5
Part B-Placebo	1.0	± 1.2

Changes in Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) Total Score From Baseline Secondary · 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.

30 minutes

Group	Value	95% CI
Part A-30 mcg BXCL501	-2.2	± 1.6
Part A-60 mcg BXCL501	-1.7	± 2.2
Part A-Placebo	-0.6	± 1.4
Part B-40 Mcg-BXCL501	-1.0	± 2.4
Part B-Placebo	-1.0	± 1.7

1 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	-3.6	± 1.9
Part A-60 mcg BXCL501	-5.4	± 3.6
Part A-Placebo	-2.3	± 2.0
Part B-40 Mcg-BXCL501	-5.7	± 4.4
Part B-Placebo	-1.9	± 3.2

4 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	-6.8	± 4.4
Part A-60 mcg BXCL501	-8.1	± 2.5
Part A-Placebo	-4.1	± 3.6
Part B-40 Mcg-BXCL501	-6.5	± 4.5
Part B-Placebo	-2.8	± 4.8

8 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	-7.1	± 4.6
Part A-60 mcg BXCL501	-8.8	± 3.1
Part A-Placebo	-4.6	± 3.3
Part B-40 Mcg-BXCL501	-5.0	± 4.3
Part B-Placebo	-3.2	± 4.7

Day 2; 24 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	-5.7	± 4.0
Part A-60 mcg BXCL501	-6.0	± 3.8
Part A-Placebo	-4.3	± 3.3
Part B-40 Mcg-BXCL501	-3.4	± 3.7
Part B-Placebo	-2.4	± 4.0

Day 3

Group	Value	95% CI
Part A-30 mcg BXCL501	-5.3	± 5.0
Part A-60 mcg BXCL501	-5.9	± 4.2
Part A-Placebo	-3.9	± 3.7
Part B-40 Mcg-BXCL501	-3.2	± 3.3
Part B-Placebo	-1.8	± 2.7

Day 7

Group	Value	95% CI
Part A-30 mcg BXCL501	-4.9	± 3.9
Part A-60 mcg BXCL501	-4.6	± 3.9
Part A-Placebo	-3.4	± 4.4
Part B-40 Mcg-BXCL501	-2.5	± 4.1
Part B-Placebo	-1.5	± 1.5

Number of Patients at Each Dose Who Achieve a 40% Reduction From Baseline in PEC Total Score at 2 Hours Post-dose ("Responders") Secondary · 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.

Group	Value	95% CI
Part A-30 mcg BXCL501	4
Part A-60 mcg BXCL501	14
Part A-Placebo	1
Part B-40 Mcg-BXCL501	9
Part B-Placebo	2

Change in Clinician Global Impression of Severity (CGI-S) Agitation Score From Baseline Secondary · 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 en

2 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	-1.3	± 0.8
Part A-60 mcg BXCL501	-2.1	± 0.9
Part A-Placebo	-0.9	± 0.9
Part B-40 Mcg-BXCL501	-2.2	± 1.3
Part B-Placebo	-0.7	± 1.0

24 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	-1.4	± 1.1
Part A-60 mcg BXCL501	-1.6	± 0.9
Part A-Placebo	-1.2	± 1.1
Part B-40 Mcg-BXCL501	-1.2	± 1.1
Part B-Placebo	-0.7	± 1.2

Clinical Global Impression - Improvement (CGI-I) Agitation Score Secondary · 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.

30 minutes

Group	Value	95% CI
Part A-30 mcg BXCL501	3.3	± 0.2
Part A-60 mcg BXCL501	3.4	± 0.2
Part A-Placebo	3.5	± 0.2
Part B-40 Mcg-BXCL501	3.5	± 0.1
Part B-Placebo	3.7	± 0.1

1 hour

Group	Value	95% CI
Part A-30 mcg BXCL501	3.0	± 0.2
Part A-60 mcg BXCL501	2.6	± 0.2
Part A-Placebo	3.3	± 0.2
Part B-40 Mcg-BXCL501	2.5	± 0.2
Part B-Placebo	3.5	± 0.2

2 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	2.4	± 0.2
Part A-60 mcg BXCL501	1.6	± 0.2
Part A-Placebo	3.2	± 0.2
Part B-40 Mcg-BXCL501	1.9	± 0.2
Part B-Placebo	3.6	± 0.2

4 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	2.4	± 0.3
Part A-60 mcg BXCL501	1.5	± 0.2
Part A-Placebo	3.0	± 0.3
Part B-40 Mcg-BXCL501	2.0	± 0.3
Part B-Placebo	3.3	± 0.3

8 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	2.3	± 0.2
Part A-60 mcg BXCL501	1.4	± 0.2
Part A-Placebo	3.0	± 0.2
Part B-40 Mcg-BXCL501	2.5	± 0.3
Part B-Placebo	3.5	± 0.3

Change in Cohen Mansfield Agitation Inventory (CMAI) Total Score From Baseline Secondary · 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.

2 hours

Group	Value	95% CI
Part A-30 mcg BXCL501	-8.9	± 5.1
Part A-60 mcg BXCL501	-14.7	± 9.8
Part A-Placebo	1.6	± 4.5
Part B-40 Mcg-BXCL501	-17.9	± 22.7
Part B-Placebo	-5.7	± 14.0

Day 7

Group	Value	95% CI
Part A-30 mcg BXCL501	-5.9	± 4.3
Part A-60 mcg BXCL501	-6.6	± 6.7
Part A-Placebo	0.4	± 9.8
Part B-40 Mcg-BXCL501	-6.9	± 17.7
Part B-Placebo	-1.4	± 4.5

Number of Patients With Event "Time Taken for Medication to Dissolve" Secondary · 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.

1- 30 seconds

Group	Value	95% CI
Part A-30 mcg BXCL501	0
Part A-60 mcg BXCL501	0
Part A- 90 mcg BXCL501	0
Part A-Placebo	0
Part B-40 Mcg-BXCL501	0
Part B-Placebo	0

31- 59 seconds

Group	Value	95% CI
Part A-30 mcg BXCL501	0
Part A-60 mcg BXCL501	0
Part A- 90 mcg BXCL501	0
Part A-Placebo	0
Part B-40 Mcg-BXCL501	0
Part B-Placebo	2

1- 2 minutes

Group	Value	95% CI
Part A-30 mcg BXCL501	10
Part A-60 mcg BXCL501	8
Part A- 90 mcg BXCL501	2
Part A-Placebo	8
Part B-40 Mcg-BXCL501	12
Part B-Placebo	10

3+ minutes

Group	Value	95% CI
Part A-30 mcg BXCL501	6
Part A-60 mcg BXCL501	12
Part A- 90 mcg BXCL501	2
Part A-Placebo	6
Part B-40 Mcg-BXCL501	11
Part B-Placebo	11

Number of Patients Showing Negative Reaction to Sublingual Film in the Examiner's Opinion Secondary · 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.

30 minutes Post dose

Group	Value	95% CI
Part A-30 mcg BXCL501	0
Part A-60 mcg BXCL501	0
Part A- 90 mcg BXCL501	0
Part A-Placebo	0
Part B-40 Mcg-BXCL501	0
Part B-Placebo	0

2 hours post dose

Group	Value	95% CI
Part A-30 mcg BXCL501	0
Part A-60 mcg BXCL501	0
Part A- 90 mcg BXCL501	0
Part A-Placebo	0
Part B-40 Mcg-BXCL501	0
Part B-Placebo	0

4 hours post dose

Group	Value	95% CI
Part A-30 mcg BXCL501	0
Part A-60 mcg BXCL501	0
Part A- 90 mcg BXCL501	0
Part A-Placebo	0
Part B-40 Mcg-BXCL501	0
Part B-Placebo	0

24 hours post dose

Group	Value	95% CI
Part A-30 mcg BXCL501	0
Part A-60 mcg BXCL501	0
Part A- 90 mcg BXCL501	0
Part A-Placebo	0
Part B-40 Mcg-BXCL501	0
Part B-Placebo	0

Part B: Change From Baseline in the Total Score of 3 Supplementary Items of Positive and Negative Syndrome Scale (PANSS) Secondary · 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.

Group	Value	95% CI
Part B-40 Mcg-BXCL501	-3.7	± 2.9
Part B-Placebo	-0.6	± 2.3

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 7 post-dose. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A-30 mcg BXCL501

Serious: 0/16 (0%)

Deaths: 0/16

Part A-60 mcg BXCL501

Serious: 0/20 (0%)

Deaths: 0/20

Part A- 90 mcg BXCL501

Serious: 0/4 (0%)

Deaths: 0/4

Part A-Placebo

Serious: 0/14 (0%)

Deaths: 0/14

Part B-40 Mcg-BXCL501

Serious: 1/23 (4%)

Deaths: 1/23

Part B-Placebo

Serious: 0/23 (0%)

Deaths: 0/23

Serious adverse events (2 terms)

Reaction	System	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
Sepsis	Infections and infestations	—	—	—	—	—	—
Hypernatraemia	Metabolism and nutrition disorders	—	—	—	—	—	—

Other adverse events (12 terms — click to expand)

Reaction	System	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
Somnolence	Nervous system disorders	—	—	—	—	—	—
Orthostatic hypotension	Vascular disorders	—	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—
Bradycardia	Cardiac disorders	—	—	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—

Most-reported serious reactions: Sepsis, Hypernatraemia.

Data from ClinicalTrials.gov NCT04251910 adverse events section.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Alzheimer's disease drug development pipeline: 2022.
   Cummings J, Lee G, Nahed P, Kambar MEZN, et al · · 2022 · cited 369× · PMID 35516416 · DOI 10.1002/trc2.12295
2. Alzheimer's disease drug development pipeline: 2021.
   Cummings J, Lee G, Zhong K, Fonseca J, et al · · 2021 · cited 312× · PMID 34095440 · DOI 10.1002/trc2.12179
3. An Update on Apathy in Alzheimer's Disease.
   Dolphin H, Dyer AH, McHale C, O'Dowd S, et al · · 2023 · cited 19× · PMID 37489323 · DOI 10.3390/geriatrics8040075
4. Severe hypotension following sublingual dexmedetomidine administration in an elderly patient.
   Coralic Z, Allai M, Hwang C, Michaels B, et al · · 2026 · PMID 41351540 · DOI 10.1093/ajhp/zxaf335
5. Agitation in Alzheimer's disease: From assessment to therapeutics.
   Teixeira AL, Kim Y, Cordeiro TM, de Erausquin GA, et al · · 2025 · PMID 41281504 · DOI 10.5498/wjp.v15.i11.109581