Study to Compare PT007 to Placebo MDI and Open-Label Proventil® HFA in Adult and Adolescent Subjects With Asthma

Study Overview
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Brief Summary
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This is a randomized, double-blind, single-dose, placebo-controlled, 5-period, 5-treatment, crossover, multi-center study to assess the bronchodilatory effect and safety of 2 dose levels of Albuterol Sulfate Pressurized Inhalation Suspension (hereafter referred to as AS MDI), 90 μg and 180 μg, compared with placebo for AS MDI (hereafter referred to as Placebo MDI) and open-label Proventil® hydrofluoroalkane (HFA; hereafter referred to as Proventil) 90 μg and 180 μg in adult and adolescent subjects with mild to moderate asthma. This study design utilizes 10 treatment sequences.

Detailed Description
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This is a 5-period crossover study. Each Treatment Period is 1 day. Subjects will receive a single dose of randomized study drug at each of the 5 Treatment Visits (Visits 2, 3, 4, 5, and 6), with a 3- to 7-day Washout Period between Treatment Visits.

Official Title
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A Randomized, Double-blind, Single Dose, Placebo-controlled, 5-Period, 5-Treatment, Crossover, Multi-center, Dose-ranging Study to Compare PT007 to Placebo MDI and Open-Label Proventil® HFA in Adult and Adolescent Subjects With Mild to Moderate Asthma (ANTORA)

Conditions
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Asthma

Intervention / Treatment
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* Drug: AS MDI 90 μg
* Drug: AS MDI 180 µg
* Other: Placebo MDI
* Drug: Proventil 90 μg
* Drug: Proventil 180 μg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Are at least 12 years of age and no older than 65 years Have stable (for 6 months) physician-diagnosed asthma with historical documentation of the diagnosis Must be receiving 1 of the following required inhaled asthma therapies listed below for at least the last 30 days; Only SABA, which is used as needed for rescue, or Low to medium doses of ICS (alone or in combination with LABA), used regularly as maintenance asthma therapy Demonstrate acceptable spirometry performance (ie, meet American Thoracic Society [ATS]/European Respiratory Society [ERS] acceptability/repeatability criteria Pre-bronchodilator FEV1 of ≥40 to <90% predicted normal value after withholding SABA for ≥6 hours Confirmed FEV1 reversibility to Ventolin, defined as a post-Ventolin increase in FEV1 of ≥15% only 2 reversibility testing attempts are allowed Exclusion Criteria: Chronic obstructive pulmonary disease or other significant lung disease (eg, chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, or bronchopulmonary dysplasia) Oral corticosteroid use (any dose) within 6 weeks Current smokers, former smokers with >10 pack-years history, or former smokers who stopped smoking <6 months (including all forms of tobacco, e-cigarettes [vaping], and marijuana) Life-threatening asthma as defined as any history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s) Historical or current evidence of a clinically significant disease Cancer not in complete remission for at least 5 years Hospitalized for psychiatric disorder or attempted suicide within 1 year Unable to abstain from protocol-defined prohibited medications during the study

Ages Eligible for Study
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Minimum Age: 12 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: • AS MDI 90 µg<br>(2 actuations of 45 µg/actuation) | Drug: AS MDI 90 μg<br>* AS MDI 90 μg (2 actuations of 45 μg/actuation)<br>* Other names: AS MDI;|
| Experimental: • AS MDI 180 µg<br>(2 actuations of 90 µg/actuation) | Drug: AS MDI 180 µg<br>* AS MDI 180 μg (2 actuations of 90 μg/actuation)<br>* Other names: AS MDI;|
| Placebo Comparator: • Placebo MDI<br>(2 actuations) | Other: Placebo MDI<br>* Placebo MDI (2 actuations)<br>|
| Active Comparator: • Proventil 90 µg<br>(1 actuation of 90 µg/actuation) | Drug: Proventil 90 μg<br>* Proventil 90 μg (1 actuation of 90 μg/actuation)<br>* Other names: Proventil;|
| Active Comparator: • Proventil 180 µg<br>(2 actuations of 90 µg/actuation) | Drug: Proventil 180 μg<br>* Proventil 180 μg (2 actuations of 90 μg/actuation)<br>* Other names: Proventil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in FEV1 AUC0-6 | Change from baseline in FEV1 (Forced expiratory volume in 1 second) AUC0-6 (Area under the curve from 0 to 6 hours) (spirometry will be obtained at 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose) normalized for length of follow up. | Over 6 hours post dose on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in FEV1 AUC0-4 | Change from baseline in FEV1 (Forced expiratory volume in 1 second) AUC0-4 (Area under the curve from 0 to 4 hours) (spirometry will be obtained at 5, 15, 30, 45, 60, 120, 180, and 240 minutes post-dose) normalized for length of follow up. | Over 4 hours post dose on Day 1 | 
| Peak Change From Baseline in FEV1 | Peak Change from baseline in FEV1 (Forced expiratory volume in 1 second) | Over 6 hours post dose on Day 1 |