Agitation Associated With Bipolar DisorderPhase 3SERENITY IINCT04276883
Dexmedetomidine in the Treatment of Agitation Associated With Bipolar Disorder
A Phase 3 study testing Sublingual film containing Dexmedetomidine (BXCL501) in people with Agitation Associated With Bipolar Disorder and Agitation,Psychomotor, run by BioXcel Therapeutics Inc at 15 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Agitation Associated With Bipolar Disorder, Agitation,Psychomotor, Bipolar Disorder
- What is being tested?
- Sublingual film containing Dexmedetomidine (BXCL501)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 380 participants
- Where
- 15 sitesUnited States
- Study dates
- 24 Feb 2020to 21 May 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients between the ages of 18 to 75 years, inclusive.
- Patients who have met DSM-5 criteria for bipolar I or II disorder.
- 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).
- Patients who have a score of ≥ 4 on at least 1 of the 5 items on the PEC at Baseline.
- Patients who read, understand and provide written informed consent.
- 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.
- Participants who agree to use a medically acceptable and effective birth control method
Who cannot join
- 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.
- Use of benzodiazepines or other hypnotics or oral or short-acting intramuscular antipsychotic drugs in the 4 hours before study treatment.
- Treatment with alpha-1 noradrenergic blockers (terazosin, doxazosin, tamsulosin, alfuzosin, or prazosin) or other prohibited medications.
- Patients who are judged to be at significant risk of suicide.
- Female patients who have a positive pregnancy test at screening or are breastfeeding.
- 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.
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- History of syncope or other syncopal attacks, current evidence of hypovolemia, orthostatic hypotension.
- Patients with laboratory or ECG abnormalities considered clinically significant by the investigator.
- Patients with serious or unstable medical illnesses.
- Patients who have received an investigational drug within 30 days prior to the current agitation episode.
- Patients who are considered by the investigator, for any reason, to be an unsuitable candidate for receiving DEX.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
BioXcel Clinical Research Site
Austin, Texas, 78754
BioXcel Clinical Research Site
Berlin, New Jersey, 08009
BioXcel Clinical Research Site
Cerritos, California, 90703
BioXcel Clinical Research Site
Charleston, South Carolina, 29407
BioXcel Clinical Research Site
Chicago, Illinois, 60640
BioXcel Clinical Research Site
Culver City, California, 90230
BioXcel Clinical Research Site
DeSoto, Texas, 75115
BioXcel Clinical Research Site
Gaithersburg, Maryland, 20877
BioXcel Clinical Research Site
Las Vegas, Nevada, 89102
BioXcel Clinical Research Site
Little Rock, Arkansas, 72211
BioXcel Clinical Research Site
Long Beach, California, 90806
BioXcel Clinical Research Site
Marlton, New Jersey, 08053
BioXcel Clinical Research Site
Miami Lakes, Florida, 33016
BioXcel Clinical Research Site
Orange, California, 92868
BioXcel Clinical Research Site
Richardson, Texas, 75080
About this study
Official title: A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine Efficacy and Safety of BXCL501 In Agitation Associated With Bipolar Disorder
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.
Read the 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.
- Being tested
- Sublingual film containing Dexmedetomidine (BXCL501), Placebo Film
- Medical subject headings
- Psychomotor Agitation, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sublingual film containing Dexmedetomidine (BXCL501)Drug
Also called Dexmedetomidine
Sublingual film containing Dexmedetomidine (BXCL501)
Placebo FilmDrug
Also called Placebo
Placebo Film for BXCL501
| Study group | Role | What they receive |
|---|---|---|
| 120 Micrograms | Experimental | Sublingual film containing 120 Micrograms Dexmedetomidine Receives: Drug: Sublingual film containing Dexmedetomidine (BXCL501) |
| 180 Micrograms | Experimental | Sublingual film containing 180 Micrograms Dexmedetomidine Receives: Drug: Sublingual film containing Dexmedetomidine (BXCL501) |
| Placebo | Placebo comparator | Sublingual placebo film Receives: Drug: Placebo Film |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline and 120 minutes
Secondary outcomes (1)
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).
Measured: Baseline and 20, 30, 45, 60, 90, 120 minutes post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2020
- Study start24 Feb 2020
- Primary completion21 May 2020
- Study completion21 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Agitation Associated With Bipolar DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- phase III, randomized, double-blind, placebo-controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 380 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioXcel Therapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cognitive Research Corporation
- Responsible party
- Sponsor
- Investigators
- BioXcel MM, Study chair, BioXcel Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04276883
- Sponsor's protocol ID
- BXCL501-302
- Acronym
- SERENITY II
- Status last verified
- Aug 2026
- First submitted
- 18 Feb 2020
- Last updated
- 11 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Citrome L, Risinger R, Rajachandran L, Robison H. Sublingual Dexmedetomidine for Agitation Associated with Schizophrenia or Bipolar Disorder: A Post Hoc Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed. Adv Ther. 2022 Oct;39(10):4821-4835. doi: 10.1007/s12325-022-02274-3. Epub 2022 Aug 24.
PubMed 36002761Preskorn SH, Zeller S, Citrome L, Finman J, Goldberg JF, Fava M, Kakar R, De Vivo M, Yocca FD, Risinger R. Effect of Sublingual Dexmedetomidine vs Placebo on Acute Agitation Associated With Bipolar Disorder: A Randomized Clinical Trial. JAMA. 2022 Feb 22;327(8):727-736. doi: 10.1001/jama.2022.0799.
PubMed 35191924
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine Efficacy and Safety of BXCL501 In Agitation Associated With Bipolar Disorder
- ClinicalTrials.gov ID
- NCT04276883
- Acronym / sponsor ID
- SERENITY II / BXCL501-302
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 380 participants (actual)
- Lead sponsor
- BioXcel Therapeutics IncIndustry (pharma, biotech, devices)
- Collaborators
- Cognitive Research Corporation
- Study start
- 24 Feb 2020 (actual)
- Primary completion
- 21 May 2020 (actual)
- Study completion
- 21 May 2020 (actual)
- First posted
- 19 Feb 2020 (actual)
- Results
- Posted 11 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- phase III, randomized, double-blind, placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| 120 Micrograms | Experimental | Drug: Sublingual film containing Dexmedetomidine (BXCL501)Sublingual film containing 120 Micrograms Dexmedetomidine |
| 180 Micrograms | Experimental | Drug: Sublingual film containing Dexmedetomidine (BXCL501)Sublingual film containing 180 Micrograms Dexmedetomidine |
| Placebo | Placebo comparator | Drug: Placebo FilmSublingual placebo film |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male and female patients between the ages of 18 to 75 years, inclusive.
- Patients who have met DSM-5 criteria for bipolar I or II disorder.
- 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).
- Patients who have a score of ≥ 4 on at least 1 of the 5 items on the PEC at Baseline.
- Patients who read, understand and provide written informed consent.
Key exclusion criteria (11 listed)
- 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.
- Use of benzodiazepines or other hypnotics or oral or short-acting intramuscular antipsychotic drugs in the 4 hours before study treatment.
- Treatment with alpha-1 noradrenergic blockers (terazosin, doxazosin, tamsulosin, alfuzosin, or prazosin) or other prohibited medications.
- Patients who are judged to be at significant risk of suicide.
- Female patients who have a positive pregnancy test at screening or are breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sublingual film containing Dexmedetomidine (BXCL501)Also: DexmedetomidineSublingual film containing Dexmedetomidine (BXCL501) | Drug | 120 Micrograms, 180 Micrograms |
| Placebo FilmAlso: PlaceboPlacebo Film for BXCL501 | Drug | Placebo |
Primary outcome
Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score
Time frame: 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).
1 secondary outcome
Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time
Time frame: Baseline and 20, 30, 45, 60, 90, 120 minutes post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36002761Citrome L, Risinger R, Rajachandran L, Robison H. Sublingual Dexmedetomidine for Agitation Associated with Schizophrenia or Bipolar Disorder: A Post Hoc Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed. Adv Ther. 2022 Oct;39(10):4821-4835. doi: 10.1007/s12325-022-02274-3. Epub 2022 Aug 24.
- Derived from this study: PubMed 35191924Preskorn SH, Zeller S, Citrome L, Finman J, Goldberg JF, Fava M, Kakar R, De Vivo M, Yocca FD, Risinger R. Effect of Sublingual Dexmedetomidine vs Placebo on Acute Agitation Associated With Bipolar Disorder: A Randomized Clinical Trial. JAMA. 2022 Feb 22;327(8):727-736. doi: 10.1001/jama.2022.0799.
Related trials for Agitation Associated With Bipolar Disorder
RecruitingPhase 1
Determining Efficacy and Safety of BXCL501 in Agitation Associated With Pediatric Schizophrenia and Bipolar Disorder
Schizophrenia, Schizo-Affective Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
BioXcel MM study chair
BioXcel Therapeutics
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sublingual film containing Dexmedetomidine (BXCL501) in people with Agitation Associated With Bipolar Disorder and Agitation,Psychomotor, run by BioXcel Therapeutics Inc at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score (time frame: Baseline and 120 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04276883, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.