A Study of Staccato Loxapine (ADASUVE®) for Inhalation

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 schizophrenic or bipolar disorder patients.

Detailed Description
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This is a multi-center, randomized, double-blind, placebo-controlled, parallel group, efficacy and safety study of Staccato Loxapine or placebo in treating acute agitation in patients with schizophrenia or bipolar disorder (manic or mixed episodes) as defined by DSM-V criteria.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 Efficacy and Safety Study of Staccato Loxapine (ADASUVE®) for Inhalation in Acutely Agitated Patients With Schizophrenia or Bipolar Disorder

Conditions
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Psychomotor Agitation, Schizophrenia, Bipolar Disorder

Intervention / Treatment
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* Drug: Inhaled loxapine
* Drug: Inhaled placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Male and female patients between the ages of 18 to 65 years, inclusive. 2. Patients who met Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria for schizophrenia or bipolar disorder. 3. Patients are judged to be clinical mild to moderate agitation at baseline with a total value of ≥ 14, and have a score ≥4 on at least 1 of 5 items on the PANSS-EC scale, and with a value of ≥3 on CGI-S scale. 4. Patients are judged to be cooperative by the Investigator. 5. Written informed consent from patients (and/or legally acceptable representative, legally acceptable representative preferred) is obtained. Exclusion Criteria: 1. Patients with agitation caused primarily by Delirium, Dpilepsy, Developmental Retardation, acute alcohol or psychoactive drugs intoxication/withdrawal symptoms (as per Investigator's judgment). 2. Patients judged to be at serious risk for suicide as per the Investigator's judgement. 3. Patients with a history of allergy or intolerance to loxapine or amoxapine. 4. Female patients of childbearing potential who have a positive urine pregnancy test at screening or breastfeeding. 5. Patients with acute respiratory signs/symptoms (e.g., wheezing) or with active airways disease (such as patients with asthma or chronic obstructive pulmonary disease). 6. Patients who are considered by the Investigator, for any reason, to be unsuitable candidates for receiving inhaled loxapine, or are likely to be unable to use the inhalation device.

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 |
| --- | --- |
| Experimental: Inhaled loxapine<br>Inhaled Loxapine 9.1 mg, may repeat x 1 or 2 after 2 hours | Drug: Inhaled loxapine<br>* Inhaled Loxapine 9.1 mg, may repeat x 1 or 2 after 2 hours<br>* Other names: ADASUVE;|
| Placebo Comparator: Inhaled placebo<br>Inhaled placebo, may repeat x 1 or 2 after 2 hours | Drug: Inhaled placebo<br>* Inhaled placebo, may repeat x 1 or 2 after 2 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PANSS-EC From Baseline | 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. | Time Frame: Baseline and 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PANSS-EC From Baseline |  | Baseline and 30 minutes | 
| Change in PANSS-EC From Baseline |  | Baseline and 4 hours | 
| Change in PANSS-EC From Baseline |  | Baseline and 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, bipolar disorder, agitation, inhaled loxapine, ADASUVE