Clinical trial NCT04276883: Dexmedetomidine in the Treatment of Agitation Associated With Bipolar Disorder
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Agitation Associated With Bipolar Disorder
Agitation,Psychomotor
Bipolar Disorder
Lead sponsor: BioXcel Therapeutics Inc
Sponsor class: INDUSTRY
Collaborators: name: Cognitive Research Corporation
First posted: 2020-02-19
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: phase III, randomized, double-blind, placebo-controlled
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score
timeFrame: Baseline and 120 minutes
Secondary outcomes:
measure: Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time
timeFrame: Baseline and 20, 30, 45, 60, 90, 120 minutes post-dose
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: BioXcel Clinical Research Site
state: Arkansas
city: Cerritos
country: United States
facility: BioXcel Clinical Research Site
state: California
city: Culver City
country: United States
facility: BioXcel Clinical Research Site
state: California
city: Long Beach
country: United States
facility: BioXcel Clinical Research Site
state: California
city: Orange
country: United States
facility: BioXcel Clinical Research Site
state: California
city: Miami Lakes
country: United States
facility: BioXcel Clinical Research Site
state: Florida
city: Chicago
country: United States
facility: BioXcel Clinical Research Site
state: Illinois
city: Gaithersburg
country: United States
facility: BioXcel Clinical Research Site
state: Maryland
city: Las Vegas
country: United States
facility: BioXcel Clinical Research Site
state: Nevada
city: Berlin
country: United States
facility: BioXcel Clinical Research Site
state: New Jersey
city: Marlton
country: United States
facility: BioXcel Clinical Research Site
state: New Jersey
city: Charleston
country: United States
facility: BioXcel Clinical Research Site
state: South Carolina
city: Austin
country: United States
facility: BioXcel Clinical Research Site
state: Texas
city: DeSoto
country: United States
facility: BioXcel Clinical Research Site
state: Texas
city: Richardson
country: United States
facility: BioXcel Clinical Research Site
state: Texas
Study officials:
References:
citation: 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.
citation: Preskorn 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.