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

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.

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.