BXCL501 for Agitation in Schizophrenia

Study Overview
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Brief Summary
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Agitation is characterized by excessive motor or verbal activity, irritability, uncooperativeness, threatening gestures, and, in some cases, aggressive or violent behavior. While agitation may have various underlying causes, patients with schizophrenia are especially vulnerable to acute episodes of agitation, especially during exacerbation of disease, and clinicians do not always diagnose these episodes early enough. Agitation associated with psychosis is a frequent reason for emergency department visits, and unless it is recognized early and managed effectively, it can rapidly escalate to potentially dangerous behaviors, including physical violence. Educating psychiatric professionals about the timely and accurate diagnosis of agitation among patients with schizophrenia or bipolar disorder and developing a well-tolerated easily administered medication will contribute to the prompt and effective management of this condition and could help reduce the risk of violent behavior and other undesirable outcomes. This study is designed to identify the ideal dose range and tolerability of sublingual Dexmedetomidine in patients with schizophrenia.

Official Title
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Safety and Efficacy of BXCL501, a Sublingual Film Delivery of Dexmedetomidine for the Treatment of Acute Agitation in Schizophrenia

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: Dexmedetomidine Hydrochloride
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to give informed consent. Male or female between 18 and 65 years of age, inclusive According to DSM-V meet criteria for Schizophrenia or Schizoaffective disorder. Exclusion Criteria: Current significant medical condition or other comorbidities Current substance dependence Women who are pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The subjects will be randomized and will get either a sublingual formulation of dexmedetomidine or placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Order 1<br>Subjects will be given a sublingual formulation of BXCL501 (dexmedetomidine) | Drug: Dexmedetomidine Hydrochloride<br>* Dexmedetomidine Hydrochloride<br>* Other names: Precedex;|
| Placebo Comparator: Order 2<br>Subjects will be given a sublingual film of placebo. | Drug: Placebos<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Symptom Scale Excited Component (PANSS-EC) | PANSS-EC comprises 5 items associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement; each scored from 1 (minimum) to 7 (maximum). The PANSS-EC is the sum of these 5 subscales and ranges from 5 to 35. | Measured at screening, prior to dosing, every 30 minutes post drug administration, and the day following drugadministration. | 
| Skin conductance response (SCR) | SCR is one of the fastest-responding measures of stress response and arousal. Along with changes in heart rate, it has been found to be one of the most robust and non-invasive physiological measures of autonomic nervous system activity. | Measured continuously from approximatley 15 minutes prior to drug administatration until the end of the test day (approximately 11 hours) | 
| Heart rate variability | Heart rate variability (HRV) is a measure of the variability in time intervals between heart beats and is sensitive to sympathetic activity as well as worsening of psychosis/agitation. | Measured continuously from approximatley 15 minutes prior to drug administatration until the end of the test day (approximately 11 hours) | 
| Blood pressure | Systolic and diastolic blood pressure | Measured at screening, prior to administartion, approximately every 15 minutes post drug administration, and one day after drug administration | 
| Agitation-Calmness Scale (ACES) | Designed to assess the clinical levels of calmness and sedation. This is a 9-point scale that differentiates between agitation, calmness, and sleep states Scores range from 1 (marked agitation)-9 (unarousable). | Measured at screening, prior to administration, approximately every 30 minutes post dose, and one day following drug administration. | 
| Richmond Agitation Sedation Scale (RASS) | The RASS is a 10-level rating scale ranging from Combative (+4) to unarousable (-5). | Measured at screening, prior to administration, approximately every 30 minutes post dose, and one day following drug administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behavioral Activity Rating Scale (BARS) | Ranging from 1 to 7 where: 1 = difficult or unable to rouse, 2 = asleep but responds normally to verbal or physical contact, 3 = drowsy, appears sedated, 4 = quiet, and awake (normal level of activity), 5 = signs of overt (physical or verbal) activity, calms down with instructions, 6 = extremely or continuously active, not requiring restraint, 7 = violent, requires restraint. | Measured at screening, prior to administration, approximately every 30 minutes post dose, and one day following drug administration. | 
| Clinical Global Impressions-Improvement Scale (CGI-I) | Clinical Global Impression- Improvement (CGI-I) scores ranged from 1 to 7: 0=not assessed (missing), 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. | Measured at screening, prior to dosing, every 30 minutes post drug administration, and the day following drugadministration. | 
| Adverse Effects | To determine any adverse effects on blood pressure, heart rate, or respiratory drive occurs before or coincident with the achievement of the aforementioned level of sedation. | Assessed prior to dosing, throughout study drug administration, and up to one week after drug administration |