Agitation Associated With Bipolar Disorder, Agitation,Psychomotor, Bipolar Disorder
Conditions
Brief summary
This is a definitive study to support the safety and efficacy evaluation of BXCL501 for the acute treatment of agitation in bipolar disorder. The BXCL501-302 study is designed to characterize the efficacy, safety and tolerability of BXCL501 (sublingual film formulation of DEX, HCl) in agitation associated with bipolar disorder.
Detailed description
The study will enroll approximately 375 subjects randomized 1:1:1 to dose regimens of 180µg, 120µg BXCL501, or placebo stratified by age \< 65 and age ≥ 65. Male and female adults with acute agitation associated with bipolar disorder will be enrolled. Eligible subjects (acutely agitated subjects with bipolar disorder, generally hypomanic, manic or mixed episodes) may be identified in outpatient clinics, mental health, psychiatric or medical emergency services including medical/psychiatric observation units, or as newly admitted to a hospital setting for acute agitation or already in hospital for chronic underlying conditions. Subjects will be domiciled in a clinical research setting or hospitalized to remain under medical supervision while undergoing screening procedures to assess eligibility. Efficacy and safety assessments will be conducted periodically before and after dosing.
Interventions
Sublingual film containing Dexmedetomidine (BXCL501)
DRUGPlacebo Film
Placebo Film for 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
Double-blind, placebo-controlled
Intervention model description
phase III, randomized, double-blind, placebo-controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female patients between the ages of 18 to 75 years, inclusive. 2. Patients who have met DSM-5 criteria for bipolar I or II disorder. 3. Patients who are judged to be clinically agitated at Screening and Baseline with a total score of ≥ 14 on the 5 items (poor impulse control, tension, hostility, uncooperativeness, and excitement) comprising the PANSS Excited Component (PEC). 4. Patients who have a score of ≥ 4 on at least 1 of the 5 items on the PEC at Baseline. 5. Patients who read, understand and provide written informed consent. 6. Patients who are in good general health prior to study participation as determined by a detailed medical history, physical examination, 12-lead ECG with rhythm strip, blood chemistry profile, hematology, urinalysis, and in the opinion of the Principal Investigator. 7. Participants who agree to use a medically acceptable and effective birth control method
Exclusion criteria
1. Patients with agitation caused by acute intoxication, including positive identification of alcohol by breathalyzer or drugs of abuse (with the exception of THC) during urine screening. 2. Use of benzodiazepines or other hypnotics or oral or short-acting intramuscular antipsychotic drugs in the 4 hours before study treatment. 3. Treatment with alpha-1 noradrenergic blockers (terazosin, doxazosin, tamsulosin, alfuzosin, or prazosin) or other prohibited medications. 4. Patients who are judged to be at significant risk of suicide. 5. Female patients who have a positive pregnancy test at screening or are breastfeeding. 6. Patients who have hydrocephalus, seizure disorder, or history of significant head trauma, stroke, transient ischemic attack, subarachnoid bleeding, brain tumor, encephalopathy, meningitis, Parkinson's disease or focal neurological findings. 7. History of syncope or other syncopal attacks, current evidence of hypovolemia, orthostatic hypotension. 8. Patients with laboratory or ECG abnormalities considered clinically significant by the investigator. 9. Patients with serious or unstable medical illnesses. 10. Patients who have received an investigational drug within 30 days prior to the current agitation episode. 11. Patients who are considered by the investigator, for any reason, to be an unsuitable candidate for receiving DEX.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Baseline and 120 minutes | The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items-poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Baseline and 20, 30, 45, 60, 90, 120 minutes post-dose | Effect on agitation onset was measured by change from baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) total score. The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items -poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe). |
Countries
United States
Contacts
STUDY_CHAIRBioXcel MM
BioXcel Therapeutics
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 180 Micrograms Sublingual film containing 180 Micrograms Dexmedetomidine
Sublingual film containing Dexmedetomidine (BXCL501): Sublingual film containing Dexmedetomidine (BXCL501) | 126 |
| 120 Micrograms Sublingual film containing 120 Micrograms Dexmedetomidine
Sublingual film containing Dexmedetomidine (BXCL501): Sublingual film containing Dexmedetomidine (BXCL501) | 126 |
| Placebo Sublingual placebo film
Placebo Film: Placebo Film for BXCL501 | 126 |
| Total | 378 |
Baseline characteristics
| Characteristic | 180 Micrograms | 120 Micrograms | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 45.9 years STANDARD_DEVIATION 11.3 | 46.1 years STANDARD_DEVIATION 11.5 | 44.8 years STANDARD_DEVIATION 12.1 | 45.6 years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 12 Participants | 11 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 111 Participants | 114 Participants | 115 Participants | 340 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Positive and Negative Syndrome Scale-Excited Component (PEC) | 18.0 units on a scale STANDARD_DEVIATION 3 | 18.0 units on a scale STANDARD_DEVIATION 2.7 | 17.9 units on a scale STANDARD_DEVIATION 2.9 | 18.0 units on a scale STANDARD_DEVIATION 2.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 72 Participants | 68 Participants | 72 Participants | 212 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 49 Participants | 56 Participants | 50 Participants | 155 Participants |
| Sex: Female, Male Female | 67 Participants | 67 Participants | 73 Participants | 207 Participants |
| Sex: Female, Male Male | 59 Participants | 59 Participants | 53 Participants | 171 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 126 | 0 / 126 | 0 / 126 |
| other Total, other adverse events | 45 / 126 | 44 / 126 | 19 / 126 |
| serious Total, serious adverse events | 0 / 126 | 1 / 126 | 0 / 126 |
Outcome results
Primary
Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score
The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items-poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe).
Time frame: Baseline and 120 minutes
Population: Intent-to-Treat population, defined as all participants in the safety population who have a PEC score post-dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 180 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Change from Baseline at 120 Minutes | -10.4 score on a scale | Standard Deviation 4.45 |
| 180 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Baseline | 18.0 score on a scale | Standard Deviation 2.99 |
| 120 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Change from Baseline at 120 Minutes | -9.0 score on a scale | Standard Deviation 5.26 |
| 120 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Baseline | 18.0 score on a scale | Standard Deviation 2.73 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Baseline | 17.9 score on a scale | Standard Deviation 2.94 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Change from Baseline at 120 Minutes | -4.9 score on a scale | Standard Deviation 4.67 |
p-value: <0.0001Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
Secondary
Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time
Effect on agitation onset was measured by change from baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) total score. The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items -poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe).
Time frame: Baseline and 20, 30, 45, 60, 90, 120 minutes post-dose
Population: Intent-to-Treat population, defined as all participants in the safety population who have a PEC score post-dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 180 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 60 minutes | -8.4 score on a scale | Standard Deviation 5.17 |
| 180 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 90 minutes | -9.7 score on a scale | Standard Deviation 4.9 |
| 180 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 120 minutes | -10.4 score on a scale | Standard Deviation 4.45 |
| 180 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 30 minutes | -4.6 score on a scale | Standard Deviation 5.08 |
| 180 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Baseline | 18 score on a scale | Standard Deviation 2.99 |
| 180 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 45 minutes | -6.7 score on a scale | Standard Deviation 5.12 |
| 180 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 20 minutes | -3.1 score on a scale | Standard Deviation 4.45 |
| 120 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Baseline | 18 score on a scale | Standard Deviation 2.73 |
| 120 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 45 minutes | -6.3 score on a scale | Standard Deviation 5.3 |
| 120 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 90 minutes | -8.6 score on a scale | Standard Deviation 5.28 |
| 120 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 20 minutes | -2.9 score on a scale | Standard Deviation 3.83 |
| 120 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 30 minutes | -4.3 score on a scale | Standard Deviation 4.86 |
| 120 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 120 minutes | -9.0 score on a scale | Standard Deviation 5.26 |
| 120 Micrograms | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 60 minutes | -7.5 score on a scale | Standard Deviation 5.19 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 120 minutes | -4.9 score on a scale | Standard Deviation 4.67 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 60 minutes | -4.4 score on a scale | Standard Deviation 4.53 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Baseline | 17.9 score on a scale | Standard Deviation 2.94 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 20 minutes | -1.9 score on a scale | Standard Deviation 3 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 30 minutes | -2.8 score on a scale | Standard Deviation 3.85 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 45 minutes | -3.6 score on a scale | Standard Deviation 4.14 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Change from Baseline at 90 minutes | -4.7 score on a scale | Standard Deviation 4.52 |
Comparison: 180 Micrograms versus placebo; 120 minutes post-dosep-value: <0.0001Mixed Models Analysis
Comparison: 120 Micrograms versus placebo; 120 minutes post-dosep-value: <0.0001Mixed Models Analysis
Comparison: 180 Micrograms versus placebo; 90 minutes post-dosep-value: <0.0001Mixed Models Analysis
Comparison: 120 Micrograms versus placebo; 90 minutes post-dosep-value: <0.0001Mixed Models Analysis
Comparison: 180 Micrograms versus placebo; 60 minutes post-dosep-value: <0.0001Mixed Models Analysis
Comparison: 120 Micrograms versus placebo; 60 minutes post-dosep-value: <0.0001Mixed Models Analysis
Comparison: 180 Micrograms versus placebo; 45 minutes post-dosep-value: <0.0001Mixed Models Analysis
Comparison: 120 Micrograms versus placebo; 45 minutes post-dosep-value: <0.0001Mixed Models Analysis
Comparison: 180 Micrograms versus placebo; 30 minutes post-dosep-value: 0.0006Mixed Models Analysis
Comparison: 120 Micrograms versus placebo; 30 minutes post-dosep-value: 0.0028Mixed Models Analysis
Comparison: 180 Micrograms versus placebo; 20 minutes post-dosep-value: 0.007Mixed Models Analysis
Comparison: 120 Micrograms versus placebo; 20 minutes post-dosep-value: 0.0092Mixed Models Analysis