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

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 criteriafor bipolar I or bipolar II disorder, schizophrenia, schizoaffective orschizophreniform disorder.

• Patients who, in the opinion of the Principal Investigator, are in good generalhealth before study participation based on a detailed medical history, a physicalexamination, a 12-lead ECG, a blood chemistry profile, hematology, and urinalysis.

• Participants who agree to use a medically acceptable and effective birth controlmethod

Part 1 only

• Patients who are judged to be clinically agitated at Screening and Baseline with atotal 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 anintervention (e.g., receipt of as needed [PRN] medication for the episode, clinicvisit, emergency room visit, emergency medical services intervention, lawenforcement intervention) in the past three months prior to Screening

• Patients who are receiving stable psychotropic treatment for 30 days prior toScreening for the underlying primary diagnosis and who are expected to remain onstable treatment for the duration of the study.

• The patient can understand and follow the study procedures, including completing theAgitation 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, ornarcissistic personality disorder that predated the diagnosis of schizophrenia orbipolar 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 arebreastfeeding.

• Patients currently treated with alpha-1 noradrenergic blockers (terazosin,doxazosin, tamsulosin, alfuzosin, or prazosin), alpha-2 adrenergic agonists, orother prohibited medications.

• Patients with hydrocephalus, seizure disorder, or history of significant headtrauma, 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, ororthostatic hypotension

• Patients with laboratory or ECG abnormalities considered clinically significant bythe Investigator

• Patients who have received an investigational drug within 30 days before the studystart

• Patients who have previously received BXCL501 via prescription (under the trade nameIGALMI™) or received BXCL501 in clinical trial

• Patients considered by the Investigator to be unsuitable candidates for receivingdexmedetomidine or considered to be unsuitable for participating in the study forany reason.

Part 1 only

• Patients with agitation caused by acute intoxication, including identification ofalcohol by breathalyzer or drugs of abuse (except for THC) during urine screening.

• Use of benzodiazepines or other hypnotics or antipsychotic drugs in the 4 hoursbefore study treatment.

Part 2 only

• Psychiatric comorbidities are generally allowed; however, moderate or severesubstance use disorders (SUD) (within the past 6 months) are exclusionary if thesubstance involved is other than nicotine or caffeine. Cannabis use is notexclusionary if it is not the focus of treatment in the last 6 months beforeScreening.

• 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 studyper 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 AgitationEpisode Diary and other study procedures during the study.

• Willing and able to accompany patient and remain present at the clinical site duringthe clinic visits and be interviewed by the Investigator.