Dexmedetomidine in the Treatment of Agitation Associated With Schizophrenia and Bipolar Disorder (SERENITY III)

NCT05658510 | Completed Phase 3 FDA Drug

• 1 other identifier: BXCL501-401
• Study Type: interventional
• Target: 452
• Locations: 1 country
• Sites: 24

Brief Summary

In this study, an investigational medication named BXCL501 is being tested for the treatment of episodes of agitation associated with bipolar I and bipolar II disorder, schizophrenia, schizoaffective and schizophreniform disorder. This study compares the study drug to a placebo.

Conditions

Agitation,Psychomotor; Bipolar I Disorder; Bipolar II Disorder; Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorders

Outcome Measures

Primary Outcomes (2)

• Part 1: Change from baseline in Positive and Negative Syndrome Scale - Excited (PEC) total score

  The Positive and Negative Syndrome Scale - Excited Component (PEC) comprises 5 items associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement; each scored 1 (minimum) to 7 (maximum). The PEC, the sum of these 5 subscales, thus ranges from 5 (absence of agitation) to 35 (extremely severe)

  2 hours

• Part 2: The incidence of SAEs and TEAEs compared with placebo.

  To assess the safety of 120 mcg BXCL501 when used in an at-home environment based on serious adverse events (SAE) and treatment emergent adverse events (TEAEs).

  Through study completion, an average of 12 weeks

Secondary Outcomes (13)

• Part 1: Clinical Global Impression - Improvement (CGI-I)

  2 hours

• Part 1: Change in Modified Clinical Global Impression - Severity (mCGI-S) scores from Baseline

  2 hours

• Part 1:The number of responders based on the Modified Clinical Global Impression - Severity (mCGI-S) score

  2 hours

• Part 1:Change from baseline in Agitation-Calmness Evaluation Scale (ACES)

  2 hours

• Part 1: Incidence of treatment-emergent adverse events (TEAEs)

  Through study completion, an average of 8 hours

Study Arms (4)

Part 1: 60 mcg of BXCL501

EXPERIMENTAL

Sublingual film containing 60 Micrograms Dexmedetomidine

Drug: BXCL501

Part 1: Matching Placebo

PLACEBO COMPARATOR

Sublingual Placebo film

Drug: Matching Placebo

Part 2: 120 mcg of BXCL501

EXPERIMENTAL

Sublingual film containing 120 Micrograms Dexmedetomidine

Drug: BXCL501

Part 2: Matching Placebo

PLACEBO COMPARATOR

Sublingual Placebo film

Drug: Matching Placebo

Interventions

BXCL501 DRUG

Sublingual Film

Also known as: Dexmedetomidine

Part 1: 60 mcg of BXCL501; Part 2: 120 mcg of BXCL501

Matching Placebo DRUG

Sublingual Placebo Film

Also known as: Placebo

Part 1: Matching Placebo; Part 2: Matching Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients between the ages of 18 to 75 years, inclusive
• Patients who can read, understand and provide written informed consent.
• Patients who have met Diagnostic and Statistical Manual5/5-Text Revision criteria for bipolar I or bipolar II disorder, schizophrenia, schizoaffective or schizophreniform disorder.
• Patients who, in the opinion of the Principal Investigator, are in good general health before study participation based on a detailed medical history, a physical examination, a 12-lead ECG, a blood chemistry profile, hematology, and urinalysis.
• Participants who agree to use a medically acceptable and effective birth control method
• Part 1 only
• 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 PEC.
• Patients with a score of ≥4 on at least 1 of the 5 items on the PEC at Baseline.
• Part 2 only
• Patients have had at least three clinical presentations of agitation requiring an intervention (e.g., receipt of as needed \[PRN\] medication for the episode, clinic visit, emergency room visit, emergency medical services intervention, law enforcement intervention) in the past three months prior to Screening
• Patients who are receiving stable psychotropic treatment for 30 days prior to Screening for the underlying primary diagnosis and who are expected to remain on stable treatment for the duration of the study.
• The patient can understand and follow the study procedures, including completing the Agitation Episode Diary.

You may not qualify if:

• Patients with serious or unstable medical illnesses. These include current hepatic (moderate-severe hepatic impairment), renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease, congestive heart failure), endocrinologic, or hematologic disease.
• A history of agitation episodes due to substance use.
• A diagnosis of antisocial personality disorder, borderline personality disorder, or narcissistic personality disorder that predated the diagnosis of schizophrenia or bipolar disorder
• Patients who are judged to be at significant risk of suicide
• Female patients who have a positive pregnancy test at Screening or Baseline, or are breastfeeding.
• Patients currently treated with alpha-1 noradrenergic blockers (terazosin, doxazosin, tamsulosin, alfuzosin, or prazosin), alpha-2 adrenergic agonists, or other prohibited medications.
• Patients with 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.
• History of syncope or other syncopal attacks, current evidence of hypovolemia, or orthostatic hypotension
• Patients with laboratory or ECG abnormalities considered clinically significant by the Investigator
• Patients who have received an investigational drug within 30 days before the study start
• Patients who have previously received BXCL501 via prescription (under the trade name IGALMI™) or received BXCL501 in clinical trial
• Patients considered by the Investigator to be unsuitable candidates for receiving dexmedetomidine or considered to be unsuitable for participating in the study for any reason.
• Part 1 only
• Patients with agitation caused by acute intoxication, including identification of alcohol by breathalyzer or drugs of abuse (except for THC) during urine screening.
• Use of benzodiazepines or other hypnotics or antipsychotic drugs in the 4 hours before study treatment.

Sponsors & Collaborators

• BioXcel Therapeutics Inc: lead
• Worldwide Clinical Trials: collaborator

Study Sites (24)

BioXcel Clinical Research Site 113

Bellflower, California, 90706, United States

Location

BioXcel Clinical Research Site 128

Cerritos, California, 90703, United States

Location

BioXcel Clinical Research Site 110

Culver City, California, 90230, United States

Location

BioXcel Clinical Research Site 108

Garden Grove, California, 92845, United States

Location

BioXcel Clinical Research Site 117

Lemon Grove, California, 91945, United States

Location

BioXcel Clinical Research Site 121

Los Angeles, California, 90015, United States

Location

BioXcel Clinical Research Site 123

Oceanside, California, 92056, United States

Location

BioXcel Clinical Research Site 104

Orange, California, 92868, United States

Location

BioXcel Clinical Research Site 133

Rancho Cucamonga, California, 91730, United States

Location

BioXcel Clinical Research Site 114

Riverside, California, 92506, United States

Location

BioXcel Clinical Research Site 129

Denver, Colorado, 80209, United States

Location

BioXcel Clinical Research Site 131

Miami, Florida, 33122, United States

Location

BioXcel Clinical Research Site 124

Miami, Florida, 33186, United States

Location

BioXcel Clinical Research Site 130

Elgin, Illinois, 60123, United States

Location

BioXcel Clinical Research Site 103

Gaithersburg, Maryland, 20877, United States

Location

BioXcel Clinical Research Site 118

Las Vegas, Nevada, 89102, United States

Location

BioXcel Clinical Research Site 137

Las Vegas, Nevada, 89119, United States

Location

BioXcel Clinical Research Site 105

Berlin, New Jersey, 08009, United States

Location

BioXcel Clinical Research Site 122

Beachwood, Ohio, 44122, United States

Location

BioXcel Clinical Research Site 136

Austin, Texas, 78754, United States

Location

BioXcel Clinical Research Site 102

DeSoto, Texas, 75115, United States

Location

BioXcel Clinical Research Site 125

Irving, Texas, 75062, United States

Location

BioXcel Clinical Research Site 127

Plano, Texas, 75093, United States

Location

BioXcel Clinical Research Site 126

Everett, Washington, 98201, United States

Location

MeSH Terms

Conditions

Psychomotor Agitation; Bipolar Disorder; Schizophrenia; Psychotic Disorders

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Matt Mandel, MD

  BioXcel Therapeutics

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind placebo controlled.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1: Patients randomized to receive 60 mcg of BXCL501 or a matching placebo. Part 2: Patients randomized to receive 120 mcg of BXCL501 or a matching placebo.

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: December 20, 2022
• Study Start: November 21, 2022
• Primary Completion: August 15, 2025
• Study Completion: August 15, 2025
• Last Updated: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (24)