Clinical trial NCT05658510: Dexmedetomidine in the Treatment of Agitation Associated With Schizophrenia and Bipolar Disorder (SERENITY III)
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Agitation,Psychomotor
Bipolar I Disorder
Bipolar II Disorder
Schizophrenia
Schizoaffective Disorder
Schizophreniform Disorders
Lead sponsor: BioXcel Therapeutics Inc
Sponsor class: INDUSTRY
Collaborators: name: Worldwide Clinical Trials
First posted: 2022-12-20
Enrollment: 452
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed description: This is a randomized, double-blind, placebo-controlled, 2-Part, Phase III study to assess the efficacy, safety, and tolerability 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 of 60 mcg dose, and post-treatment observation period with patients experiencing an acute episode of agitation. Part 1 is now complete. Part 2 of the study is a 12-week study to determine the safety of a BXCL501 120 mcg dose when used as needed for episodes of agitation at home.

Eligibility criteria: 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 (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.

Exclusion Criteria:

* 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.

Part 2 only

* Psychiatric comorbidities are generally allowed; however, moderate or severe substance use disorders (SUD) (within the past 6 months) are exclusionary if the substance involved is other than nicotine or caffeine. Cannabis use is not exclusionary if it is not the focus of treatment in the last 6 months before Screening.
* Self-injurious behavior that is active.
* Patients with known personal or family history of genetic long QT syndrome.

Informant Inclusion Criteria:

* At least 18 years of age at the time of screening.
* Is a spouse, significant other, family member, friend, or home health aide, residence manager of an adult patient who is determined to be eligible for the study per the patient inclusion/exclusion criteria.
* Has known the patient for at least 3 months cumulatively.
* Currently living with or routinely contacting the patient at least five days a week.
* Does not plan to discontinue contact with the patient during the study period.
* Willing and able to provide written informed consent.
* Willing and able to follow the study procedures, including completing the Agitation Episode Diary and other study procedures during the study.
* Willing and able to accompany patient and remain present at the clinical site during the clinic visits and be interviewed by the Investigator.

Primary outcomes:
measure: Part 1: Change from baseline in Positive and Negative Syndrome Scale - Excited (PEC) total score
timeFrame: 2 hours
measure: Part 2: The incidence of SAEs and TEAEs compared with placebo.
timeFrame: Through study completion, an average of 12 weeks
Secondary outcomes:
measure: Part 1: Clinical Global Impression - Improvement (CGI-I)
timeFrame: 2 hours
measure: Part 1: Change in Modified Clinical Global Impression - Severity (mCGI-S) scores from Baseline
timeFrame: 2 hours
measure: Part 1:The number of responders based on the Modified Clinical Global Impression - Severity (mCGI-S) score
timeFrame: 2 hours
measure: Part 1:Change from baseline in Agitation-Calmness Evaluation Scale (ACES)
timeFrame: 2 hours
measure: Part 1: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Through study completion, an average of 8 hours
measure: Part 1: Change from baseline in heart rate (HR) at rest
timeFrame: Baseline, and 2, 4, 6, and 8 hours postdose
measure: Part 1: Change from baseline in heart rate (HR) under orthostatic stress
timeFrame: Baseline, and 2, 4, 6, and 8 hours postdose
measure: Part 1: Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at rest
timeFrame: Baseline, and 2, 4, 6, and 8 hours postdose
measure: Part 1: Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) under orthostatic stress
timeFrame: Baseline, and 2, 4, 6, and 8 hours postdose
measure: Part 1: Incidence of abnormal electrocardiograms (ECG) reported as an adverse event (AE)
timeFrame: Through study completion, an average of 8 hours
measure: Part 1: Incidence of abnormal clinical laboratory values reported as an adverse event (AE)
timeFrame: Through study completion, an average of 8 hours
measure: Part 2: Incidence of interactions with emergency services related to agitation
timeFrame: Through study completion, an average of 12 weeks
measure: Part 2: Incidence of overall adverse events and AEs leading to discontinuation
timeFrame: Through study completion, an average of 12 weeks
Other outcomes:
Locations:
city: Bellflower
country: United States
facility: BioXcel Clinical Research Site 113
state: California
city: Cerritos
country: United States
facility: BioXcel Clinical Research Site 128
state: California
city: Culver City
country: United States
facility: BioXcel Clinical Research Site 110
state: California
city: Garden Grove
country: United States
facility: BioXcel Clinical Research Site 108
state: California
city: Lemon Grove
country: United States
facility: BioXcel Clinical Research Site 117
state: California
city: Los Angeles
country: United States
facility: BioXcel Clinical Research Site 121
state: California
city: Oceanside
country: United States
facility: BioXcel Clinical Research Site 123
state: California
city: Orange
country: United States
facility: BioXcel Clinical Research Site 104
state: California
city: Rancho Cucamonga
country: United States
facility: BioXcel Clinical Research Site 133
state: California
city: Riverside
country: United States
facility: BioXcel Clinical Research Site 114
state: California
city: Denver
country: United States
facility: BioXcel Clinical Research Site 129
state: Colorado
city: Miami
country: United States
facility: BioXcel Clinical Research Site 131
state: Florida
city: Miami
country: United States
facility: BioXcel Clinical Research Site 124
state: Florida
city: Elgin
country: United States
facility: BioXcel Clinical Research Site 130
state: Illinois
city: Gaithersburg
country: United States
facility: BioXcel Clinical Research Site 103
state: Maryland
city: Las Vegas
country: United States
facility: BioXcel Clinical Research Site 118
state: Nevada
city: Las Vegas
country: United States
facility: BioXcel Clinical Research Site 137
state: Nevada
city: Berlin
country: United States
facility: BioXcel Clinical Research Site 105
state: New Jersey
city: Beachwood
country: United States
facility: BioXcel Clinical Research Site 122
state: Ohio
city: Austin
country: United States
facility: BioXcel Clinical Research Site 136
state: Texas
city: DeSoto
country: United States
facility: BioXcel Clinical Research Site 102
state: Texas
city: Irving
country: United States
facility: BioXcel Clinical Research Site 125
state: Texas
city: Plano
country: United States
facility: BioXcel Clinical Research Site 127
state: Texas
city: Everett
country: United States
facility: BioXcel Clinical Research Site 126
state: Washington
Study officials:
affiliation: BioXcel Therapeutics
name: Matt Mandel, MD
role: STUDY_CHAIR
References: