Efficacy and Safety of PT001 to Placebo and Open-label Spiriva® Respimat® in Subjects With Persistant Asthma

Study Overview
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Brief Summary
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Study Comparing the Efficacy and Safety of PT001 to Placebo and Open-label Spiriva® Respimat® in Subjects With Persistent Asthma

Detailed Description
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A Randomized, Double-Blind, Parallel Group, Multi-Center 24-Week Study Comparing the Efficacy and Safety of Three Doses of PT001 to Placebo and Open-label Spiriva® Respimat® in Subjects With Persistent Asthma

Official Title
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A Randomized, Double-Blind, Parallel Group, Multi-Center 24-Week Study Comparing the Efficacy and Safety of Three Doses of PT001 to Placebo and Open-label Spiriva® Respimat® in Subjects With Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: GP MDI 28.8 μg
* Drug: GP MDI 14.4 μg
* Drug: GP MDI 7.2 μg
* Drug: Placebo MDI
* Drug: Spiriva Respimat 2.5 μg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a documented history of physician-diagnosed asthma Require inhaled asthma maintenance therapy: has been regularly using an ICS/LABA on a stable regimen for at least 4 weeks Documented reversibility to albuterol A pre-bronchodilator FEV1 >40% and <85% of predicted normal value for subjects 18 to 80 years of age or >40% and <90% of predicted for subjects 12 to <18 years of age Demonstrate acceptable spirometry performance Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol Compliance: must be willing to remain at the study center as required per protocol to complete all visit assessments Exclusion Criteria: Oral corticosteroid use (any dose) within 4 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, and marijuana) Life-threatening asthma as defined as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s) Completed treatment for lower respiratory infection or asthma exacerbation within 4 weeks Hospitalizations for asthma within 3 months Historical or current evidence of a clinically significant disease Cancer not in complete remission for at least 5 years Treatment with investigational study drug (or device) in another clinical study within the last 30 days or 5 half-lives, whichever is longer Previously randomized in any PT001 study

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 80 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
Interventional Model Description: Linear repeated measures model
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GP MDI 28.8 μg<br>GP MDI 14.4 μg per actuation taken as 2 inhalations BID | Drug: GP MDI 28.8 μg<br>* GP MDI (PT001)14.4 μg per actuation taken as 2 inhalations BID<br>* Other names: GP;|
| Experimental: GP MDI 14.4 μg<br>GP MDI 7.2 μg per actuation taken as 2 inhalations BID | Drug: GP MDI 14.4 μg<br>* GP MDI (PT001) 7.2 μg per actuation taken as 2 inhalations BID<br>* Other names: GP;|
| Experimental: GP MDI 7.2 μg<br>GP MDI 3.6 μg per actuation taken as 2 inhalations BID | Drug: GP MDI 7.2 μg<br>* GP MDI (PT001) 3.6 μg per actuation taken as 2 inhalations BID<br>* Other names: GP;|
| Placebo Comparator: Placebo MDI<br>Taken as 2 inhalations BID | Drug: Placebo MDI<br>* Placebo taken as 2 inhalations BID<br>* Other names: Placebo;|
| Other: Spiriva Respimat 2.5 μg<br>Open Label Spiriva Respimat 2.5 μg | Drug: Spiriva Respimat 2.5 μg<br>* Spiriva Respimat 2.5 μg QD (open-label)<br>* Other names: Spiriva Respimat;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 to 4 Hours (AUC0-4) | Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 4 hours (AUC0-4)AUC was normalized for length of follow up (e.g. typically 4 hours). | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Morning Pre-dose Trough FEV1 |  | Week 24 | 
| Rate of Moderate to Severe Asthma Exacerbations | Rate of moderate to severe Asthma exacerbations (A deterioration of asthma requiring a new or increased dose of ICS for at least 3 days) or severe Asthma exacerbation (Use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days OR a hospitalization or ER visit because of asthma) | over 24 Weeks (timepoints of 4, 12 & 20 weeks) | 
| Change From Baseline in ACQ-7 (Asthma Control Questionnaire) | ACQ-7: The ACQ, comprising 7 questions, is completed in the clinic and requires subjects to recall their experiences during the previous week (7 days) prior to the study visit. The ACQ-5 measures 5 symptoms (woken at night by symptoms, wake in the morning with symptoms, limitation of daily activities, shortness of breath, and wheeze); the ACQ-6 is these symptom measurements plus daily rescue medication use as recalled by the subject; and the ACQ 7 is the ACQ 6 plus airway caliber as measured by pre-bronchodilator FEV1 percent predicted. Each question is scored on a 7-point scale (generally, 0=no impairment, 6=maximum impairment), the questions are equally weighted, and the ACQ score is the mean of the item responses and therefore ranges from 0 (totally controlled) to 6 (severely uncontrolled. | Week 24 | 
| Change From Baseline in ACQ-5 (Asthma Control Questionnaire) | ACQ-5:The ACQ-5 measures 5 symptoms (woken at night by symptoms, wake in the morning with symptoms, limitation of daily activities, shortness of breath, and wheeze). Each question is scored on a 7-point scale (generally, 0=no impairment, 6=maximum impairment), the questions are equally weighted, and the ACQ score is the mean of the item responses and therefore ranges from 0 (totally controlled) to 6 (severely uncontrolled). | Week 24 | 
| Change From Baseline in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ +12) | AQLQ +12 - Asthma Quality of Life Questionnaire The AQLQ +12 is a 32-item validated subject-administered questionnaire that was developed to measure the functional problems (physical, emotional, social and occupational) that are most troublesome to adults (≥18 years of age) and adolescents (12 to 17 years of age) with asthma. The 32 questions in the AQLQ +12 are in 4 domains (symptoms, activity limitation, emotional function, and environmental stimuli). All 4 domains contain standard specific questions relating to each domain. Subjects are asked to think about how they have been during the previous 2 weeks. Responses to each of the 32 questions are on a 7-point scale (7=no impairment to 1=severe impairment). The overall AQLQ +12 score is the mean of all 32 responses. Overall scores range from 1=severe impairment to 7=no impairment. | Week 24 |