Staccato Loxapine Thorough QT/QTc Study

Study Overview
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Brief Summary
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The purpose of the present Phase 1 study was to assess the cardiac safety of Staccato Loxapine administered to healthy volunteers in a 3 period crossover study.

Detailed Description
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Primary Objective: To assess the maximum effect of Staccato Loxapine on cardiac repolarization (QTc interval duration) at the anticipated maximum clinical dose compared to placebo in healthy volunteers. Secondary Objective: To assess the QTc versus loxapine concentration relationship following treatment with Staccato Loxapine in healthy volunteers.

Official Title
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Thorough QT/QTc Study of Staccato® Loxapine for Inhalation in Healthy Volunteers

Conditions
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Thorough QT/QTc Study

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who are in good general health and agree to use a medically acceptable and effective birth control method throughout the study. Exclusion Criteria: Subjects who have taken prescription or nonprescription medication within 5 days of treatment, Subjects who have had an acute illness within the last 5 days of treatment, Subjects who are smokers, OR Subjects who have an ECG abnormality at baseline.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment sequence ABC<br>Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg | Drug: Inhaled loxapine<br>* Inhaled Staccato Loxapine 10 mg single dose<br>* Other names: ADASUVE;Drug: Inhaled placebo<br>* Inhaled Staccato placebo single dose<br>Drug: Oral moxifloxacin<br>* Oral moxifloxacin 400 mg<br>Drug: Oral placebo<br>* Oral placebo similar in appearance to moxifloxacin 400 mg<br>|
| Other: Treatment sequence ACB<br>Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg | Drug: Inhaled loxapine<br>* Inhaled Staccato Loxapine 10 mg single dose<br>* Other names: ADASUVE;Drug: Inhaled placebo<br>* Inhaled Staccato placebo single dose<br>Drug: Oral moxifloxacin<br>* Oral moxifloxacin 400 mg<br>Drug: Oral placebo<br>* Oral placebo similar in appearance to moxifloxacin 400 mg<br>|
| Other: Treatment sequence BCA<br>Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg | Drug: Inhaled loxapine<br>* Inhaled Staccato Loxapine 10 mg single dose<br>* Other names: ADASUVE;Drug: Inhaled placebo<br>* Inhaled Staccato placebo single dose<br>Drug: Oral moxifloxacin<br>* Oral moxifloxacin 400 mg<br>Drug: Oral placebo<br>* Oral placebo similar in appearance to moxifloxacin 400 mg<br>|
| Other: Treatment sequence BAC<br>Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg | Drug: Inhaled loxapine<br>* Inhaled Staccato Loxapine 10 mg single dose<br>* Other names: ADASUVE;Drug: Inhaled placebo<br>* Inhaled Staccato placebo single dose<br>Drug: Oral moxifloxacin<br>* Oral moxifloxacin 400 mg<br>Drug: Oral placebo<br>* Oral placebo similar in appearance to moxifloxacin 400 mg<br>|
| Other: Treatment sequence CAB<br>Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg | Drug: Inhaled loxapine<br>* Inhaled Staccato Loxapine 10 mg single dose<br>* Other names: ADASUVE;Drug: Inhaled placebo<br>* Inhaled Staccato placebo single dose<br>Drug: Oral moxifloxacin<br>* Oral moxifloxacin 400 mg<br>Drug: Oral placebo<br>* Oral placebo similar in appearance to moxifloxacin 400 mg<br>|
| Other: Treatment sequence CBA<br>Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg | Drug: Inhaled loxapine<br>* Inhaled Staccato Loxapine 10 mg single dose<br>* Other names: ADASUVE;Drug: Inhaled placebo<br>* Inhaled Staccato placebo single dose<br>Drug: Oral moxifloxacin<br>* Oral moxifloxacin 400 mg<br>Drug: Oral placebo<br>* Oral placebo similar in appearance to moxifloxacin 400 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Effect of ADASUVE on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo | Largest of the upper CIs of the time matched differences in QTcI values between the maximum of the mean difference from baseline of the QTcI interval after time matched placebo subtraction for ADASUVE treatment at 12 prespecified post inhalation times | 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 23 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac Repolarization Change (QTcI) Versus Loxapine Concentration Relationship Following Treatment With Staccato Loxapine in Healthy Volunteers. | QTcI change at the median loxapine concentration (32.2 mcg/mL) based on nonlinear regression of QTcI versus log of time matched serum loxapine concentrations. This analysis looks for repolarization versus concentration relationship in a positive or negative thorough QT/QTc study result. | 24 hours | 
| Numbers and % of Subjects With QTcI > 450 ms | Numbers and Percents of Subjects with QTcI exceeding 450 ms | 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 23 hours | 
| Numbers and % of Subjects With QTcI > 480 ms | Numbers and Percents of Subjects with QTcI exceeding 480 ms | 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 23 hours | 
| Numbers and % of Subjects With QTcI Change > 30 ms | Numbers and Percents of Subjects with QTcI increase from baseline exceeding 30 ms | 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 23 hours | 
| Numbers and % of Subjects With QTcI Change > 60 ms | Numbers and Percents of Subjects with QTcI increase from baseline exceeding 60 ms | 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 23 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Staccato loxapine, QT/QTc, healthy volunteers, Thorough QT/QTc study, ADASUVE, inhaled loxapine