Staccato Prochlorperazine Single Dose PK Study

Study Overview
=================
Brief Summary
-----------------
The objective of this study was to evaluate the tolerability, safety, and pharmacokinetics of inhaled prochlorperazine

Detailed Description
-----------------
The objective of this study was to evaluate the tolerability, safety, and pharmacokinetics of a single, inhaled dose of prochlorperazine (PCZ), administered as 1 or 2 puffs in healthy young volunteers.

Official Title
-----------------
Tolerability, Safety and Pharmacokinetics of a Single Dose of Staccato™ Prochlorperazine for Inhalation in Normal, Healthy Volunteers

Conditions
-----------------
Migraine

Intervention / Treatment
-----------------
* Drug: Prochlorperazine 0.5 mg IV over 5 sec
* Drug: Inhaled prochlorperazine 0.625 mg
* Drug: Inhaled prochlorperazine 1.25 mg
* Drug: Inhaled prochlorperazine 2.5 mg
* Drug: Inhaled prochlorperazine 5 mg
* Drug: Inhaled prochlorperazine 10 mg
* Drug: Inhaled placebo
* Drug: Prochlorperazine 10 mg IV over 5 sec


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects will be male or female subjects between the ages 18 to 45 years, inclusive in good general health as determined by medical history, physical examination, 12-lead ECG, spirometry, blood chemistry profile, hematology, urinalysis and in the opinion of the Principal Investigator. Exclusion Criteria: Subjects with a known history of allergy or intolerance to phenothiazines or related drugs or who have any disease, by history, physical examination, or laboratory abnormalities that in the investigator's opinion, would present undue risk to the subject, or may confound the interpretation of study results.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Stage 1: open-label, single-dose stage with 3 treatment periods divided into 2 phases Stage 2: double-blind, placebo-controlled, dose-escalation treatment period
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled prochlorperazine 0.625 mg vs IV<br>Prochlorperazine 0.5 mg IV over 5 sec crossover Inhaled prochlorperazine 0.625 mg | Drug: Prochlorperazine 0.5 mg IV over 5 sec<br>* IV Prochlorperazine for bioavailability<br>* Other names: PCZ;Drug: Inhaled prochlorperazine 0.625 mg<br>* Inhaled Staccato Prochlorperazine 0.625 mg<br>* Other names: PCZ;Drug: Prochlorperazine 10 mg IV over 5 sec<br>* Prochlorperazine 10 mg IV over 5 sec for patient qualification<br>* Other names: PCZ;|
| Experimental: Inhaled prochlorperazine 1.25 mg<br>Inhaled Staccato prochlorperazine 1.25 mg | Drug: Inhaled prochlorperazine 1.25 mg<br>* Inhaled Staccato Prochlorperazine 1.25 mg<br>* Other names: PCZ;|
| Experimental: Inhaled prochlorperazine 2.5 mg<br>Inhaled Staccato prochlorperazine 2.5 mg | Drug: Inhaled prochlorperazine 2.5 mg<br>* Inhaled Staccato Prochlorperazine 2.5 mg<br>* Other names: PCZ;|
| Experimental: Inhaled prochlorperazine 5 mg<br>Inhaled Staccato prochlorperazine 5 mg | Drug: Inhaled prochlorperazine 5 mg<br>* InhaledStaccato Prochlorperazine 5 mg<br>* Other names: PCZ;|
| Experimental: Inhaled prochlorperazine 10 mg<br>Inhaled Staccato prochlorperazine 10 mg | Drug: Inhaled prochlorperazine 10 mg<br>* InhaledStaccato Prochlorperazine 10 mg<br>* Other names: PCZ;|
| Placebo Comparator: inhaled Placebo<br>inhaled Staccato Placebo (0 mg) | Drug: Inhaled placebo<br>* Inhaled Staccato Placebo (0 mg)<br>* Other names: ADASUVE placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Peak (Tmax) | Time from dose to peak prochlorperazine concentration | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Bioavailability of Inhaled Prochlorperazine | Absolute bioavailability of inhaled prochlorperazine via AUC infinity | 24 hours | 
| Dose Proportionality of Inhaled Prochlorperazine by Power Analysis | Dose proportionality by power analysis examines the linear regression of the log-AUC versus log-Dose on a by-patient basis across all doses administered. The slope and 90% confidence interval (CI) provide a clear, quantitative (best practices) assessment of the relationship of drug delivered to dose administered. The units on such analyses are generally those of slope (rise over run), with 1.000 being perfect. Although any positive slope might be considered clinically useful, a 90% CI within the criteria of 0.800-1.250 may be considered a delivery system which is as good as it gets. | 24 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Migraine, Prochlorperazine aerosol