Dexmedetomidine in the Treatment of Agitation Associated With Bipolar Disorder (SERENITY II)

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.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder; Agitation,Psychomotor; Agitation Associated With Bipolar Disorder
• Intervention / Treatment: Drug: Sublingual film containing Dexmedetomidine (BXCL501); Drug: Placebo Film

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 Type: Interventional
• Enrollment (Actual): 380
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • BioXcel Clinical Research Site
  • California
    • Cerritos, California, United States, 90703
      • BioXcel Clinical Research Site
    • Culver City, California, United States, 90230
      • BioXcel Clinical Research Site
    • Long Beach, California, United States, 90806
      • BioXcel Clinical Research Site
    • Orange, California, United States, 92868
      • BioXcel Clinical Research Site
  • Florida
    • Miami Lakes, Florida, United States, 33016
      • BioXcel Clinical Research Site
  • Illinois
    • Chicago, Illinois, United States, 60640
      • BioXcel Clinical Research Site
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • BioXcel Clinical Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • BioXcel Clinical Research Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • BioXcel Clinical Research Site
    • Marlton, New Jersey, United States, 08053
      • BioXcel Clinical Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • BioXcel Clinical Research Site
  • Texas
    • Austin, Texas, United States, 78754
      • BioXcel Clinical Research Site
    • DeSoto, Texas, United States, 75115
      • BioXcel Clinical Research Site
    • Richardson, Texas, United States, 75080
      • BioXcel Clinical Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Sublingual placebo film	Drug: Placebo Film; Placebo Film for BXCL501; Other Names: Placebo
Experimental: 120 Micrograms; Sublingual film containing 120 Micrograms Dexmedetomidine	Drug: Sublingual film containing Dexmedetomidine (BXCL501); Sublingual film containing Dexmedetomidine (BXCL501); Other Names: Dexmedetomidine
Experimental: 180 Micrograms; Sublingual film containing 180 Micrograms Dexmedetomidine	Drug: Sublingual film containing Dexmedetomidine (BXCL501); Sublingual film containing Dexmedetomidine (BXCL501); Other Names: Dexmedetomidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline and 120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline and 20, 30, 45, 60, 90, 120 minutes post-dose

Collaborators and Investigators

• Sponsor: BioXcel Therapeutics Inc
• Collaborators: Cognitive Research Corporation

Publications and helpful links

General 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. Erratum In: Adv Ther. 2023 Jan;40(1):391.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2020
• Primary Completion (Actual): May 21, 2020
• Study Completion (Actual): May 21, 2020

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Mood Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Dyskinesias; Psychomotor Disorders; Bipolar and Related Disorders; Psychomotor Agitation; Bipolar Disorder; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: BXCL501-302

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No