Dexmedetomidine in the Treatment of Agitation Associated With Schizophrenia (SERENITY I)

A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Study To Determine Efficacy and Safety of BXCL501 In Agitation Associated With Schizophrenia

This is a definitive study to support the safety and efficacy evaluation of BXCL501 for the acute treatment of agitation in schizophrenia. The BXCL501-301 study is designed to characterize the efficacy, safety and tolerability of BXCL501 (sublingual film formulation of DEX, HCl) in agitation associated with schizophrenia, schizoaffective disorder or schizophreniform disorder.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder; Agitation; Schizo Affective Disorder; Schizophreniform Disorders
• 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. Male and female adults with acute agitation associated with schizophrenia, schizoaffective disorder, or schizophreniform disorder will be enrolled. Eligible subjects 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, 78754
      • 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: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

A subject will be eligible for inclusion in the study if he or she meets the following criteria:

1. Male and female patients between the ages of 18 to 75 years, inclusive.
2. Patients who have met DSM-5 criteria for schizophrenia, schizoaffective, or schizophreniform 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:

A subject will be excluded from the study if he or she meets the following 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, hypnotics and anti-psychotic 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
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
Placebo Comparator: Placebo; Sublingual placebo film	Drug: Placebo Film; Placebo Film for BXCL501; Other Names: Placebo

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 2 hours

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 10, 20, 30, 45, 60, 90 minutes post-dose

Collaborators and Investigators

• Sponsor: BioXcel Therapeutics Inc
• Collaborators: Cognitive Research Corporation
• Investigators: Study Chair: Robert Risinger, MD, BioXcel Therapeutics

Publications and helpful links

General Publications

• Citrome L, Preskorn SH, Lauriello J, Krystal JH, Kakar R, Finman J, De Vivo M, Yocca FD, Risinger R, Rajachandran L. Sublingual Dexmedetomidine for the Treatment of Acute Agitation in Adults With Schizophrenia or Schizoaffective Disorder: A Randomized Placebo-Controlled Trial. J Clin Psychiatry. 2022 Oct 3;83(6):22m14447. doi: 10.4088/JCP.22m14447.
• 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.

Helpful Links

• Journal Article

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2020
• Primary Completion (Actual): May 6, 2020
• Study Completion (Actual): May 6, 2020

Study Registration Dates

• First Submitted: February 11, 2020
• First Submitted That Met QC Criteria: February 11, 2020
• First Posted (Actual): February 13, 2020

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: May 25, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Dyskinesias; Psychomotor Disorders; Schizophrenia; Psychotic Disorders; Psychomotor Agitation; Mood Disorders; 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: BXCL501-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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