Staccato Loxapine Multidose PK

Study Overview
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Brief Summary
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The objectives of this trial are to assess the safety, tolerability, and pharmacokinetics of multiple inhaled doses of Staccato Loxapine.

Detailed Description
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The purpose of the present Phase 1 study in schizophrenic patients is to assess the safety and pharmacokinetics of multiple doses of Staccato Loxapine given within a 24 hour time period. The study will be conducted in schizophrenic patients who are on chronic, stable antipsychotic medication. Patients meeting entry criteria will be randomized to one of three dose sequences of Staccato Loxapine or to Staccato Placebo. Following administration of medications, safety, tolerability and pharmacokinetic assessments will be conducted at serial time points.

Official Title
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Safety, Tolerability, and Pharmacokinetics of Multiple Doses of Staccato® Loxapine for Inhalation in Subjects on Chronic, Stable Antipsychotic Regimens

Conditions
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Volunteers on Chronic, Stable Antipsychotic Regimens

Intervention / Treatment
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* Drug: A - 10 mg loxapine q 4 h x 3 (30 mg total)
* Drug: B - 10 mg x 1, 5 mg x 2 loxapine q 4 h (20 mg total)
* Drug: C - 5 mg loxapine q 4 h x 3 (15 mg total)
* Drug: D - inhaled placebo q 4 h x 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria include: Male and female subjects between the ages of 18 to 65 years, inclusive. Subjects who are on stable, oral, chronic (>2 mos) antipsychotic medication regimen and who are able to tolerate the rapid oral dose taper and substitution regimen. Exclusion Criteria include: Subjects who are currently treated with injectable depot neuroleptics within one dose interval must be excluded. Subjects who have received loxapine or amoxapine within the last 30 days must be excluded. Subjects with a history of allergy or intolerance to dibenzoxazepines (loxapine and amoxapine) must be excluded. Subjects with a history of movement disorders including Parkinson's disease or a history of neuroleptic malignant syndrome must be excluded. Subjects who have a history within the past year of drug or alcohol dependence or abuse as defined by DSM-4 must be excluded.

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: A - 10 mg loxapine q 4 h x 3 (30 mg total)<br> | Drug: A - 10 mg loxapine q 4 h x 3 (30 mg total)<br>* loxapine aerosol inhalation high dose regimen (30 mg total)<br>* Other names: Staccato Loxapine 10 mg;|
| Experimental: B - 10 mg x 1, 5 mg x 2 loxapine q 4 h (20 mg total)<br> | Drug: B - 10 mg x 1, 5 mg x 2 loxapine q 4 h (20 mg total)<br>* loxapine aerosol inhalation middle dose regimen (20 mg total)<br>* Other names: Staccato Loxapine 5 and 10 mg;|
| Experimental: C - 5 mg loxapine q 4 h x 3 (15 mg total)<br> | Drug: C - 5 mg loxapine q 4 h x 3 (15 mg total)<br>* loxapine aerosol inhalation low dose regimen (15 mg total)<br>* Other names: Staccato Loxapine 5 mg;|
| Placebo Comparator: D - inhaled placebo q 4 h x 3<br> | Drug: D - inhaled placebo q 4 h x 3<br>* placebo aerosol inhalation (0 mg total)<br>* Other names: Staccato Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters: tmax, Cmax, AUClast, AUCinf, ke, t1/2 and clearance will be estimated for each subject and for the population using noncompartmental methods. |  | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration-time (PK) profiles will be produced for each subject and a mean PK profile for subjects completing for each dose group |  | 24 hours | 
| Tolerability will be assessed based on treatment emergent adverse events, vital signs, ECG and a visual-analog sedation scale. |  | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetic, multidose, Staccato Loxapine