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

• ClinicalTrials.gov Identifier: NCT04276883
• Recruitment Status: Completed
• First Posted: February 19, 2020
• Last Update Posted: August 19, 2020
• Sponsor: BioXcel Therapeutics Inc
• Collaborator: Cognitive Research Corporation
• Information provided by (Responsible Party): BioXcel Therapeutics Inc

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Agitation Associated With Bipolar Disorder; Agitation,Psychomotor; Bipolar Disorder	Drug: Sublingual film containing Dexmedetomidine (BXCL501); Drug: Placebo Film	Phase 3

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 378 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: phase III, randomized, double-blind, placebo-controlled
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double-blind, placebo-controlled
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 24, 2020
• Actual Primary Completion Date: May 21, 2020
• Actual Study Completion Date: May 21, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: 120 Micrograms; Sublingual film containing 120 Micrograms Dexmedetomidine	Drug: Sublingual film containing Dexmedetomidine (BXCL501); Sublingual film containing Dexmedetomidine (BXCL501)
Experimental: 180 Micrograms; Sublingual film containing 180 Micrograms Dexmedetomidine	Drug: Sublingual film containing Dexmedetomidine (BXCL501); Sublingual film containing Dexmedetomidine (BXCL501)
Placebo Comparator: Placebo; Sublingual placebo film	Drug: Placebo Film; Placebo Film for BXCL501

Outcome Measures

Primary Outcome Measures :

1. Primary End Point [ Time Frame: 120 minutes ]
   Absolute change from baseline in the PEC score at 2 hours

Secondary Outcome Measures :

1. Key Secondary Endpoint [ Time Frame: 120 minutes ]
   Earliest time where an effect on agitation is apparent as measured by change from baseline PEC total score in contrast with placebo

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Arkansas

BioXcel Clinical Research Site

Little Rock, Arkansas, United States, 72211

United States, California

BioXcel Clinical Research Site

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

United States, Florida

BioXcel Clinical Research Site

Miami Lakes, Florida, United States, 33016

United States, Illinois

BioXcel Clinical Research Site

Chicago, Illinois, United States, 60640

United States, Maryland

BioXcel Clinical Research Site

Gaithersburg, Maryland, United States, 20877

United States, Nevada

BioXcel Clinical Research Site

Las Vegas, Nevada, United States, 89102

United States, New Jersey

BioXcel Clinical Research Site

Berlin, New Jersey, United States, 08009

BioXcel Clinical Research Site

Marlton, New Jersey, United States, 08053

United States, South Carolina

BioXcel Clinical Research Site

Charleston, South Carolina, United States, 29407

United States, Texas

BioXcel Clinical Research Site

Austin, Texas, United States, 78754

BioXcel Clinical Research Site

DeSoto, Texas, United States, 75115

BioXcel Clinical Research Site

Richardson, Texas, United States, 75080

Sponsors and Collaborators

BioXcel Therapeutics Inc

Cognitive Research Corporation

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: BioXcel Therapeutics Inc
• ClinicalTrials.gov Identifier: NCT04276883
• Other Study ID Numbers: BXCL501-302
• First Posted: February 19, 2020
• Last Update Posted: August 19, 2020
• Last Verified: March 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Psychomotor Agitation; Disease; Bipolar Disorder; Pathologic Processes; Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Psychomotor Disorders; Neurobehavioral Manifestations; Dexmedetomidine; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action