Tachyphylaxis, Tolerance, & Withdrawal Post Treatment With Igalmi for Agitation in Schizophrenia or Bipolar Disorder

Study Overview
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Brief Summary
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This is an in-clinic, single arm, open-label study assessing tachyphylaxis, tolerance, and withdrawal following repeated doses of Igalmi in adult males and females with agitation associated with schizophrenia or bipolar disorder.

Detailed Description
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This is an in-clinic, single arm, open-label study assessing tachyphylaxis, tolerance, and withdrawal following repeated doses of Igalmi in adult males and females (18 to 65 years old, inclusive) with agitation associated with schizophrenia or bipolar disorder. Subjects will be screened for eligibility within 15 days of first dose and no study procedures will occur unless subjects provide written informed consent. Subjects will receive single doses of 180 μg of Igalmi as needed for the treatment of agitation over a period of 7 days followed by a 3- day follow-up period during which time no Igalmi will be administered in an effort to characterize any potential withdrawal. Subjects will sublingually self-administer Igalmi for an agitation episode that reaches a pre-dose PEC total score of 14 or greater, as determined by a trained rater. Safety assessments will be conducted before and after each dose. If the subject's agitation is recurrent or persistent, repeat doses of 90 µg may be administered (no more than 2 repeat doses within a 24-hour period) in the absence of any safety concerns or adverse events.

Official Title
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Characterization of Tachyphylaxis, Tolerance, and Withdrawal After Discontinuation of Igalmi in Frequently Agitated Schizophrenic or Bipolar Patients After 7 Days of PRN Treatment

Conditions
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Bipolar Disorder, Schizophrenia, Agitation,Psychomotor, Schizo Affective Disorder, Schizophreniform Disorders

Intervention / Treatment
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* Drug: Sublingual film containing Igalmi


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects between the ages of 18 to 65 years, inclusive. Subjects who have met DSM-5 criteria for schizophrenia, schizoaffective, or schizophreniform disorder or bipolar I or II disorder. Subjects who are currently moderate to severely agitated at least 3 days a week. Subjects who read, understand, and provide written informed consent. Subjects who are in good general health prior to study participation as determined by a detailed medical history and in the opinion of the Principal Investigator. Subjects who agree to use a medically acceptable and effective birth control method Subjects must be willing to remain in-clinic for the duration of the study. Exclusion Criteria: Subjects with agitation caused by acute intoxication, including positive identification of alcohol by breathalyzer or drugs of abuse during screening. Use of benzodiazepines or other hypnotics or antipsychotic drugs in the 6 hours before study treatment. Subjects with congenital prolonged QT syndrome. Prior treatment with Igalmi

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
Intervention Model: Single Group Assignment
Interventional Model Description: Open-Label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Active Treatment - 180 mcg of Igalmi (dexmedetomidine)<br>An initial dose of 180 µg of Igalmi as needed for the treatment of agitation over a period of 7 days. In the event of persistent or recurrent agitation, investigators may choose to repeat dose at 90 μg after the 2-hour time point in the absence of dose-limiting adverse events or safety concerns. A maximum of 2 repeat doses will be allowed in a 24-hour period. | Drug: Sublingual film containing Igalmi<br>* Sublingual film containing 180 µg of Igalmi (dexmedetomidine)<br>* Other names: BXCL501;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items-poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe). | Baseline and 2 hours post-dose for all doses administered | 
| Clinical Global Impression - Improvement (CGI-I) | The Clinical Global Impression - Improvement (CGI-I) for agitation in response to treatment measures the current level of agitation relative to the level of agitation prior to administration of study intervention. The CGI-I scores range from 1 to 7 with a score of 1 indicating very much improved, and a score of 7 indicating very much worse. | 2 hours post-dose for all doses administered | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events During the Follow-up Period | Evaluation of withdrawal phenomenon based on the occurrence of adverse events such as tachycardia, systolic hypertension, nausea, or vomiting and the emergence of any new adverse events on ≥2 consecutive days of the 3-day off-treatment follow-up period. | Day 8 through Day 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Open-Label, Agitation, Bipolar, Dexmedetomidine, tachyphylaxis, tolerance, withdrawal, PRN treatment, PEC, CGI, ACES, Safety, Tolerability, Igalmi