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

December 7, 2023 updated by: BioXcel Therapeutics Inc

Efficacy And Safety of BXCL501 Evaluated For At-Home Use In A Multisite Double-Blind Placebo-Controlled Trial For Agitation Associated With Schizophrenia And Bipolar Disorder

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.

Study Overview

Detailed Description

This is a randomized, double-blind, placebo-controlled, 2-Part, Phase III study to assess the efficacy, safety, and tolerability of a 60 mcg dose of BXCL501 in adult (18-75 years old) males and females with agitation episodes associated with a primary diagnosis of bipolar I disorder, bipolar II disorder, schizophrenia, schizoaffective disorder, or schizophreniform disorder. Part 1 of the study is a one-day, in-clinic treatment, and post-treatment observation period with patients experiencing an acute episode of agitation. Part 2 of the study is a 12-week study to determine the safety of BXCL501 when used as needed for episodes of agitation at home.

Study Type

Interventional

Enrollment (Estimated)

450

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Arkansas
      • Little Rock, Arkansas, United States, 72211
        • BioXcel Clinical Research Site 112
      • Little Rock, Arkansas, United States, 72211
        • BioXcel Clinical Research Site 119
    • California
      • Bellflower, California, United States, 90706
        • BioXcel Clinical Research Site 113
      • Cerritos, California, United States, 90703
        • BioXcel Clinical Research Site 128
      • Culver City, California, United States, 90230
        • BioXcel Clinical Research Site 110
      • Garden Grove, California, United States, 92845
        • BioXcel Clinical Research Site 108
      • Lemon Grove, California, United States, 91945
        • BioXcel Clinical Research Site 117
      • Los Angeles, California, United States, 90015
        • BioXcel Clinical Research Site 121
      • Oceanside, California, United States, 92056
        • BioXcel Clinical Research Site 123
      • Orange, California, United States, 92868
        • BioXcel Clinical Research Site 104
      • Rancho Cucamonga, California, United States, 91730
        • BioXcel Clinical Research Site 133
      • Riverside, California, United States, 92506
        • BioXcel Clinical Research Site 114
    • Colorado
      • Denver, Colorado, United States, 80209
        • BioXcel Clinical Research Site 129
    • Florida
      • Miami, Florida, United States, 33122
        • BioXcel Clinical Research Site 131
      • Miami, Florida, United States, 33186
        • BioXcel Clinical Research Site 124
      • Oakland Park, Florida, United States, 33334
        • BioXcel Clinical Research Site 134
    • Georgia
      • Atlanta, Georgia, United States, 30331
        • Bioxcel Clinical Research Site 106
      • Decatur, Georgia, United States, 30030
        • BioXcel Clinical Research Site 107
    • Illinois
      • Chicago, Illinois, United States, 60640
        • BioXcel Clinical Research Site 109
      • Elgin, Illinois, United States, 60123
        • BioXcel Clinical Research Site 130
    • Maryland
      • Gaithersburg, Maryland, United States, 20877
        • BioXcel Clinical Research Site 103
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • BioXcel Clinical Research Site 118
    • New Jersey
      • Berlin, New Jersey, United States, 08009
        • BioXcel Clinical Research Site 105
      • Marlton, New Jersey, United States, 08053
        • BioXcel Clinical Research Site 101
    • Ohio
      • Beachwood, Ohio, United States, 44122
        • BioXcel Clinical Research Site 122
    • Texas
      • DeSoto, Texas, United States, 75115
        • BioXcel Clinical Research Site 102
      • Irving, Texas, United States, 75062
        • BioXcel Clinical Research Site 125
      • Plano, Texas, United States, 75093
        • BioXcel Clinical Research Site 127
    • Utah
      • Murray, Utah, United States, 84107
        • BioXcel Clinical Research Site 120
    • Vermont
      • Rutland, Vermont, United States, 05701
        • BioXcel Clinical Research Site 132
    • Washington
      • Everett, Washington, United States, 98201
        • BioXcel Clinical Research Site 126

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

A patient may enroll in only one part of the study; either Part 1 or Part 2.

Inclusion Criteria:

  • 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 in the past three months prior to Screening
  • Patients who are receiving stable treatment for the last 3 months prior to Screening for the underlying primary diagnosis and who are expected to remain on stable treatment for the duration of the study
  • Patients who manage agitation episodes with as needed (PRN) medication
  • The patient has an Informant who can read, understand, and provide written informed consent and understand and follow the study procedures

Exclusion Criteria:

  • Patients with serious or unstable medical illnesses.
  • 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 an open-label 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.
  • Patients who have previously received BXCL501 in a clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1: 60 mcg of BXCL501
Sublingual film containing 60 Micrograms Dexmedetomidine
Sublingual Film
Other Names:
  • Dexmedetomidine
Placebo Comparator: Part 1: Matching Placebo
Sublingual Placebo film
Sublingual Placebo Film
Other Names:
  • Placebo
Placebo Comparator: Part 2: Matching Placebo
Sublingual Placebo film
Sublingual Placebo Film
Other Names:
  • Placebo
Experimental: Part 2: 80 mcg of BXCL501
Sublingual film containing 80 Micrograms Dexmedetomidine
Sublingual Film
Other Names:
  • Dexmedetomidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Change from baseline in Positive and Negative Syndrome Scale - Excited (PEC) total score
Time Frame: 2 hours
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: Incidence of treatment-emergent adverse events (TEAEs)
Time Frame: Through study completion, an average of 12 weeks
To assess the safety of BXCL501 when used in an at-home environment based on treatment-emergent adverse events (TEAEs)
Through study completion, an average of 12 weeks
Part 2: Incidence of serious adverse events (SAEs)
Time Frame: Through study completion, an average of 12 weeks
To assess the safety of BXCL501 when used in an at-home environment based on serious adverse events (SAEs)
Through study completion, an average of 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Clinical Global Impression - Improvement (CGI-I)
Time Frame: 2 hours
The Clinical Global Impression - Improvement (CGI-I) for agitation in response to treatment measures the current level of agitation relative to the level of agitation prior to administration of study intervention. The CGI-I scores range from 1 to 7 with a score of 1 indicating very much improved, and a score of 7 indicating very much worse.
2 hours
Part 1: Change in Modified Clinical Global Impression - Severity (mCGI-S) scores from Baseline
Time Frame: 2 hours
The Modified Clinical Global Impression - Severity (mCGI-S) measures the current level of agitation. For this study, the mCGI-S is a 4-point scale where a score of 0 represents no agitation, and scores of 1-3 describe increasing severities of agitation (mild, moderate, severe).
2 hours
Part 1:The number of responders based on the Modified Clinical Global Impression - Severity (mCGI-S) score
Time Frame: 2 hours
The Modified Clinical Global Impression - Severity (mCGI-S) measures the current level of agitation. A responder is characterized as a participant with a score of 0 (represents no agitation) or 1 (mild agitation)
2 hours
Part 1:Change from baseline in Agitation-Calmness Evaluation Scale (ACES)
Time Frame: 2 hours
The Agitation-Calmness Evaluation Scale (ACES) is a single item scale that measures overall agitation and sedation, where a score of 1 indicates marked agitation; 2 - moderate agitation; 3 - mild agitation; 4 - normal behavior; 5 - mild calmness; 6 - moderate calmness; 7 - marked calmness; 8 - deep sleep; and 9 - unarousable.
2 hours
Part 1: Incidence of treatment-emergent adverse events (TEAEs)
Time Frame: Through study completion, an average of 8 hours
To assess the safety of BXCL501 based on treatment-emergent adverse events (TEAEs)
Through study completion, an average of 8 hours
Part 1: Change from baseline in heart rate (HR) at rest
Time Frame: Baseline, and 2, 4, 6, and 8 hours postdose
The effect of BXCL501 on heart rate at rest
Baseline, and 2, 4, 6, and 8 hours postdose
Part 1: Change from baseline in heart rate (HR) under orthostatic stress
Time Frame: Baseline, and 2, 4, 6, and 8 hours postdose
The effect of BXCL501 on heart rate under orthostatic stress
Baseline, and 2, 4, 6, and 8 hours postdose
Part 1: Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at rest
Time Frame: Baseline, and 2, 4, 6, and 8 hours postdose
The effect of BXCL501 on systolic and diastolic blood pressure at rest
Baseline, and 2, 4, 6, and 8 hours postdose
Part 1: Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) under orthostatic stress
Time Frame: Baseline, and 2, 4, 6, and 8 hours postdose
The effect of BXCL501 on systolic and diastolic blood pressure under orthostatic stress
Baseline, and 2, 4, 6, and 8 hours postdose
Part 1: Incidence of abnormal electrocardiograms (ECG) reported as an adverse event (AE)
Time Frame: Through study completion, an average of 8 hours
Any abnormal ECG value that is reported as an adverse event (AE)
Through study completion, an average of 8 hours
Part 1: Incidence of abnormal clinical laboratory values reported as an adverse event (AE)
Time Frame: Through study completion, an average of 8 hours
Any abnormal clinical laboratory value that is reported as an adverse event (AE)
Through study completion, an average of 8 hours
Part 2: Incidence of interactions with emergency services related to agitation
Time Frame: Through study completion, an average of 12 weeks
Evaluate the impact of BXCL501 on the use of healthcare and emergency service resources because of agitation episodes
Through study completion, an average of 12 weeks
Part 2: Incidence of overall adverse events and AEs leading to discontinuation
Time Frame: Through study completion, an average of 12 weeks
To evaluate the safety and tolerability profile of BXCL501
Through study completion, an average of 12 weeks
Part 2: Proportion of patients who report somnolence (ACES score ≥8 reported by Informant) pre-dose to post-dose
Time Frame: 2 hours after each treatment for an episode of agitation
To evaluate the safety and tolerability profile of BXCL501
2 hours after each treatment for an episode of agitation
Part 2: Proportion of patients who report somnolence (KSS score ≥8 reported by patient) pre-dose to post-dose
Time Frame: 2 hours after each treatment for an episode of agitation
To evaluate the safety and tolerability profile of BXCL501
2 hours after each treatment for an episode of agitation
Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder
Time Frame: 2 hours after treatment for the first episode of agitation
Proportion of patients with an improvement in agitation (Yes/No) post-dose for the first treated episode compared with placebo
2 hours after treatment for the first episode of agitation
Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder
Time Frame: 2 hours after treatment for the first episode of agitation
Proportion of mCGI-S responders (patients who achieve a mCGI-S score of 0 or 1) following drug administration for the first treated episode
2 hours after treatment for the first episode of agitation
Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder
Time Frame: 2 hours after treatment for the first episode of agitation
Proportion of patients with a 1-point improvement in mCGI-S score following drug administration for the first treated episode
2 hours after treatment for the first episode of agitation
Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder
Time Frame: 2 hours after treatment for the first episode of agitation
Proportion of CGI-C responders (patients who achieve a CGI-C score of 1 or 2) following drug administration for the first treated episode
2 hours after treatment for the first episode of agitation
Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder
Time Frame: 2 hours after treatment for the first episode of agitation
Change in mCGI-S scores from pre-dose to post dose for the first treated episode
2 hours after treatment for the first episode of agitation
Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder
Time Frame: 2 hours after treatment for the first episode of agitation
CGI-C scores following drug administration for the first treated episode
2 hours after treatment for the first episode of agitation
Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder
Time Frame: Up to 24 hours after treatment for the first episode of agitation
Time to end of an agitation episode from dosing for the first treated episode
Up to 24 hours after treatment for the first episode of agitation
Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation
Time Frame: 2 hours after treatment for all episodes of agitation, up to 12 weeks
Proportion of patients with an improvement in agitation (Yes/No) post-dose for all treated episodes compared with placebo
2 hours after treatment for all episodes of agitation, up to 12 weeks
Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation
Time Frame: 2 hours after treatment for all episodes of agitation, up to 12 weeks
Proportion of mCGI-S responders following drug administration for the last treated episode and all treated episodes
2 hours after treatment for all episodes of agitation, up to 12 weeks
Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation
Time Frame: 2 hours after treatment for all episodes of agitation, up to 12 weeks
Proportion of patients with a 1-point improvement in mCGI-S score following drug administration for the last treated episode and all treated episodes
2 hours after treatment for all episodes of agitation, up to 12 weeks
Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation
Time Frame: 2 hours after treatment for all episodes of agitation, up to 12 weeks
Proportion of CGI-C responders following drug administration for the last treated episode and all treated episodes
2 hours after treatment for all episodes of agitation, up to 12 weeks
Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation
Time Frame: 2 hours after treatment for all episodes of agitation, up to 12 weeks
Change in mCGI-S scores from pre dose to post dose following drug administration for the last treated episode and all treated episodes
2 hours after treatment for all episodes of agitation, up to 12 weeks
Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation
Time Frame: 2 hours after treatment for all episodes of agitation, up to 12 weeks
CGI-C scores following drug administration for the last treated episode and all treated episodes
2 hours after treatment for all episodes of agitation, up to 12 weeks
Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation
Time Frame: Through study completion, an average of 12 weeks
The frequency of treated agitation episodes compared with placebo
Through study completion, an average of 12 weeks
Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation
Time Frame: Up to 24 hours after treatment for all episodes of agitation, up to 12 weeks
Time to end of an agitation episode from dosing for the last treated episode and across all treated episodes
Up to 24 hours after treatment for all episodes of agitation, up to 12 weeks
Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation
Time Frame: 2 hours after treatment for all episodes of agitation, up to 12 weeks
Change in agitation behaviors scale following drug administration
2 hours after treatment for all episodes of agitation, up to 12 weeks
Part 2: Determine the overall clinical improvement after drug administration as measured by the use of rescue medications
Time Frame: Through study completion, an average of 12 weeks
Proportion of patients who receive rescue medication compared with placebo
Through study completion, an average of 12 weeks
Part 2: Determine the overall clinical improvement after drug administration as measured by the use of rescue medications
Time Frame: Through study completion, an average of 12 weeks
Time to use of rescue medication for patients receiving BXCL501 compared with placebo
Through study completion, an average of 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Robert Risinger, MD, BioXcel Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 21, 2022

Primary Completion (Estimated)

March 30, 2025

Study Completion (Estimated)

March 30, 2025

Study Registration Dates

First Submitted

December 12, 2022

First Submitted That Met QC Criteria

December 12, 2022

First Posted (Actual)

December 20, 2022

Study Record Updates

Last Update Posted (Actual)

December 8, 2023

Last Update Submitted That Met QC Criteria

December 7, 2023

Last Verified

December 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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