Evaluating Sublingual Dexmedetomidine For Moderate To Severe Agitation In Inpatients With Schizophrenia Or Bipolar Disorder

Sponsor

Temple University (Other)

Overall Status

Recruiting

CT.gov ID

NCT06093451

Collaborator

BioXcel Therapeutics Inc (Industry)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

An open-label, randomized, active control inpatient trial to evaluate the efficacy and tolerability of sublingual dexmedetomidine for the treatment of agitation in inpatients with schizophrenia or bipolar disorder as measured by the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES). Lorazepam will serve as the active control.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Agitation Schizo Affective Disorder Bipolar Disorder Dexmedetomidine	Drug: Dexmedetomidine Drug: Lorazepam 2 MG/ML	Phase 4

Detailed Description

This is an open-label, randomized control trial where patients (N=32) with schizophrenia or bipolar disorder are randomized to receive either sublingual dexmedetomidine or oral lorazepam monotherapy for the treatment of episodic agitation. For moderate agitation (PANSS-EC score ≥14 and <20), patients will receive either sublingual dexmedetomidine 120mcg or oral lorazepam 2mg. For severe agitation (PANSS-EC ≥20), patients will receive either sublingual dexmedetomidine 180mcg or oral lorazepam 2mg. The PANSS-EC and ACES will be evaluated at baseline and after 15, 30, 60, and 120 minutes.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label, Randomized, Active Controlled Inpatient Trial Evaluating Sublingual Dexmedetomidine For Moderate To Severe Agitation In Inpatients With Schizophrenia Or Bipolar Disorder

Actual Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexmedetomidine Participants with moderate agitation will receive sublingual dexmedetomidine 120 mcg as needed. Participants with severe agitation will receive dexmedetomidine 180 mcg as needed.	Drug: Dexmedetomidine Moderate agitation: 120 mcg Severe agitation: 180 mcg Other Names: Igalmi
Active Comparator: Lorazapem Participants with moderate agitation will receive oral lorazapam 2 mgas needed. Participants with severe agitation will receive oral lorazapam 2 mg as needed.	Drug: Lorazepam 2 MG/ML 2 mg Other Names: Ativan

Arm

Intervention/Treatment

Experimental: Dexmedetomidine

Participants with moderate agitation will receive sublingual dexmedetomidine 120 mcg as needed. Participants with severe agitation will receive dexmedetomidine 180 mcg as needed.

Drug: Dexmedetomidine

Moderate agitation: 120 mcg Severe agitation: 180 mcg

Other Names:

Igalmi

Active Comparator: Lorazapem

Participants with moderate agitation will receive oral lorazapam 2 mgas needed. Participants with severe agitation will receive oral lorazapam 2 mg as needed.

Drug: Lorazepam 2 MG/ML

2 mg

Other Names:

Ativan

Outcome Measures

Primary Outcome Measures

Change in PANSS-EC score at 120 minutes after medication administration [Baseline and at 120 minutes]
Severity of agitation will be determined by administering the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC). Moderate to severe agitation will be defined as a PANSS-EC score >=14 and <20; and >= 20 is severe agitation.

Secondary Outcome Measures

Change from baseline in ACES score at 15, 30, 60, 90, and 120 minutes, or prior to receipt of any rescue medication for agitation. [Baseline and 15, 30, 60, 90, and 120 minutes]
Severity of agitation will be measured using the standardized Agitation-Calmness Evaluation Scale. The 9-point scale indicated the degree of agitation as follows: 1=marked agitation, 4=normal behavior, 7 = marked calmness, 9=unarousable.
Change in PANSS-EC score at 15, 30, 60, and 90 minutes, or prior to receipt of any rescue medication for agitation. [Baseline and 15, 30, 60, and 90 minutes]
Severity of agitation will be determined by administering the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC). Moderate to severe agitation will be defined as a PANSS-EC score >=14 and <20; and >= 20 is severe agitation.
Patient tolerability assessed by adverse events of dexmedetomidine [Baseline through 120 minutes after medication administration]
Tolerability and safety of sublingual dexmedetomidine was assessed by evaluating spontaneously-reported adverse events. Treatment tolerability as assessed by adverse events will be tabulated by toxicity grade and organ systems as well as overall.
Patient satisfaction based on Medication Satisfaction Questionnaire (MSQ) [Administered 120 minutes after medication administration]
Medication Satisfaction Questionnaire (MSQ) will be given to the subject to assess their satisfaction of their agitation medication two hours after initial medication administration. The Medication Satisfaction Questionnaire is a 7-point scale, with 1 being "Extremely Dissatisfied", 4 being "Neither Satisfied or Dissatisfied", and 7 being "Extremely Satisfied"
Assess the need for rescue medication for agitation within two hours of medication administration [Baseline and 2 hours after medication administration]
Need for rescue medication of sublingual dexmedetomidine will be assessed by reviewing the Medication Administration Reconciliation (MAR) available on the electronic medical record system for the two hour period of time following medication administration.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

The participant is an adult between the ages of 18-55 at the time of study participation
Hospitalized on an inpatient unit at Episcopal Hospital
Meet the DSM-5 criteria for schizophrenia, schizoaffective disorder, or bipolar disorder, as determined by routine clinical assessment conducted upon admission.
Are able to understand and read English
Are able to provide informed consent
Experiencing a moderate (PANSS-EC score ≥14 and <20) or severe (PANSS-EC score ≥20) episode of agitation

Exclusion Criteria:

Women who are pregnant or breastfeeding
Prisoners
Participant has an allergy to dexmedetomidine or lorazepam
Participant has mild, moderate or severe hepatic impairment
Participant has active pulmonary disease and is receiving treatment (oxygen, inhalers)
Individual is currently prescribed scheduled benzodiazepines or methadone
Participant history of QTc ≥ 500 msec or a history of arrythmia
Participant recent (within the last 2 days) fall, syncope (passing out), feeling lightheaded, or pulse <50.
Individual has a history of hypokalemia or hypomagnesemia within the past 2 years?
Participant is receiving high-risk medications, including:

Methadone
Midazolam
Opioids
High risk medications associated with the QT interval prolongation (sertindole, chlorpromazine, ziprasidone), (amiodarone, iboga, quinine, arsenic, ibutilide, selpercatinib, ivosidenib, bedaquiline, lenvatinib, sotalol, levoketoconazole, cisapride, vendetanib, mobocertinib, disopyramide, papaverine)