Staccato Loxapine in Agitated Patients With Bipolar Disorder

Study Overview
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Brief Summary
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Phase 3 safety and efficacy study of Staccato Loxapine in the treatment of acute agitation in bipolar 1 disorder patients.

Detailed Description
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This is an in-clinic, multi-center, randomized, double-blind, placebo-controlled study of 2 dose levels of Staccato Loxapine, 5 and 10 mg. Patients may receive up to 3 doses of study drug in a 24-hour period, depending on their clinical status. The primary endpoint is the change from baseline in the PANSS (Positive and Negative Symptom Scale) Excited Component (also known as PEC) score, performed at 2 hours after the first dose.

Official Title
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A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Multi-Dose Efficacy and Safety Study of Staccato® Loxapine for Inhalation in Patients With Bipolar I Disorder and Acute Agitation

Conditions
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Bipolar I Disorder

Intervention / Treatment
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* Drug: Inhaled Placebo
* Drug: Inhaled loxapine 5 mg
* Drug: Inhaled loxapine 10 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adult patients with bipolar 1 disorder and acute agitation Exclusion Criteria: Agitation caused primarily by acute intoxication History of drug or alcohol dependence Treatment with benzodiazepines or other hypnotics within 4 hours prior to study drug administration

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Inhaled Placebo<br>Inhaled Staccato Placebo, may repeat after 2 hours x 2 | Drug: Inhaled Placebo<br>* Inhaled loxapine Placebo, may repeat after 2 hours x 2<br>* Other names: Staccato Placebo;|
| Experimental: Inhaled Loxapine 5 mg<br>Inhaled Staccato Loxapine 5 mg, may repeat after 2 hours x 2 | Drug: Inhaled loxapine 5 mg<br>* Inhaled Staccato loxapine 5 mg, may repeat after 2 hours x 2<br>* Other names: ADASUVE 5 mg;|
| Experimental: Inhaled Loxapine 10 mg<br>Inhaled Staccato Loxapine 10 mg, may repeat after 2 hours x 2 | Drug: Inhaled loxapine 10 mg<br>* Inhaled Staccato loxapine 10 mg, may repeat after 2 hours x 2<br>* Other names: ADASUVE 10 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PANSS Excited Component (PEC) Score From Baseline Following Dose #1 of Staccato Loxapine, Compared With Placebo | The Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) comprises 5 items associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement; each scored 1 (min) to 7 (max). The PANSS-EC, the sum of these 5 subscales, thus ranges from 5 to 35. Individuals were eligible if they had a PANSS-EC of ≥14 (out of 35) and a score ≥4 (out of 7) on at least 1 of the 5 items. | Baseline and 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression-Improvement (CGI-I) Score Following Dose #1 of Staccato Loxapine, Compared With Placebo | 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. | Baseline and 2 hours | 
| CGI-I Responders | Frequency of response based on the CGI-I (defined as achieving a CGI-I score of 1 or 2 at 2 hours after administration of the inhalation) | Baseline and 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar 1 disorder,, agitation,, acute,, treatment