Study to Evaluate the Efficacy, Safety and Pharmacokinetics of PT001, PT003, and PT005 Following Chronic Dosing (7 Days) in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate, after 1 week of dosing, the efficacy and safety of PT003 compared with its individual components (PT001 and PT005), placebo and two active comparators to demonstrate superiority of the combination to its components, and to assess the relative contribution of the components compared with placebo, in patients with moderate to very severe COPD.

Official Title
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A Randomized, Double-Blind (Test Products and Placebo), Chronic Dosing (7 Days), Four-Period, Eight-Treatment, Placebo-Controlled, Incomplete Block, Cross-Over, Multi-Center Study to Assess Efficacy and Safety of Two Doses of PT003, Two Doses of PT005 and One Dose of PT001 in Patients With Moderate to Very Severe COPD, Compared With Foradil® Aerolizer® (12 μg, Open-Label) and Spiriva® Handihaler® (18 μg, Open-Label) as Active Controls

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: PT003 MDI
* Drug: PT005 MDI
* Drug: Placebo MDI
* Drug: Tiotropium bromide 18 μg (Spiriva Handihaler®)
* Drug: Formoterol Fumarate 12 μg (Foradil® Aerolizer®)
* Drug: PT001 MDI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent 40 - 80 years of age Clinical history of COPD with airflow limitation that is not fully reversible Females of non-child bearing potential or females of child bearing potential with negative pregnancy test; and acceptable contraceptive methods Current/former smokers with at least a 10 pack-year history of cigarette smoking A measured post- bronchodilator FEV1/FVC ratio of < or = 0.70 A measured post- bronchodilator FEV1 > or = 750ml or 30% predicted and < or = 80% of predicted normal values Able to change COPD treatment as required by protocol Exclusion Criteria: Women who are pregnant or lactating Primary diagnosis of asthma Alpha-1 antitrypsin deficiency as the cause of COPD Active pulmonary diseases Prior lung volume reduction surgery Abnormal chest X-ray (or CT scan) not due to the presence of COPD Hospitalized due to poorly controlled COPD within 3 months of Screening Clinically significant medical conditions that preclude participation in the study (e.g. clinically significant abnormal ECG, uncontrolled hypertension, glaucoma, symptomatic prostatic hypertrophy) Cancer that has not been in complete remission for at least 5 years Treatment with investigational study drug or participation in another clinical trial or study within the last 30 days or 5 half lives Other protocol defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 40 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled PT003 (Dose 1)<br>PT003 MDI Dose 1 | Drug: PT003 MDI<br>* Inhaled PT003 MDI administered as two puffs BID for 7 days<br>|
| Experimental: Inhaled PT003 (Dose 2)<br>PT003 MDI Dose 2 | Drug: PT003 MDI<br>* Inhaled PT003 MDI administered as two puffs BID for 7 days<br>|
| Experimental: Inhaled PT005 (Dose 1)<br>PT005 MDI Dose 1 | Drug: PT005 MDI<br>* Inhaled PT005 MDI administered as two puffs BID for 7 days<br>|
| Experimental: Inhaled PT005 (Dose 2)<br>PT005 MDI Dose 2 | Drug: PT005 MDI<br>* Inhaled PT005 MDI administered as two puffs BID for 7 days<br>|
| Placebo Comparator: Inhaled Placebo<br>Placebo MDI | Drug: Placebo MDI<br>* Inhaled placebo administered as two puffs BID for 7 days<br>|
| Active Comparator: Tiotropium bromide 18 μg (Spiriva Handihaler®)<br>Tiotropium Bromide inhalation powder | Drug: Tiotropium bromide 18 μg (Spiriva Handihaler®)<br>* Inhaled tiotropium bromide 18 μg (Spiriva Handihaler®) administered QD for 7 days<br>|
| Active Comparator: Formoterol Fumarate 12 μg (Foradil® Aerolizer®)<br>Formoterol fumarate inhalation powder 12 μg | Drug: Formoterol Fumarate 12 μg (Foradil® Aerolizer®)<br>* Inhaled formoterol fumarate 12 μg (Foradil® Aerolizer®) administered BID for 7 days<br>|
| Experimental: Inhaled PT001 (Dose 1)<br>PT001 MDI Dose 1 | Drug: PT001 MDI<br>* Inhaled PT001 MDI administered as two puffs BID for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 AUC 0-12 on Day 7 | Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 (normalized) relative to baseline FEV1 following 7-day dose administration | Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 10, 11.5, and 12 hours post-dose on Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Change From BL in FEV1 on Day 1 | Peak change from Baseline in FEV1 on Day 1 | Day 1 | 
| Peak Change From BL in FEV1 on Day 7 | Peak change from Baseline (BL) in FEV1 on Day 7 | Day 7 | 
| Peak Change From BL in Inspiratory Capacity on Day 1 | Peak change from Baseline in Inspiratory Capacity (IC) on Day 1 | Day 1 | 
| Peak Change From BL IC on Day 7 | Peak Change from Baseline Inspiratory Capacity on following 7-day dose administration | Day 7 | 
| Time to Onset of Action >=10% Improvement in FEV1 on Day 1 | Time to Onset of Action where the improvement in FEV1 on Day 1 was >=10% | Day 1 | 
| Percentage of Patients Achieving >=12% Improvement in FEV1 on Day 1 | Time to Onset of Action where the improvement in FEV1 on Day 1 was >= 12% | Day 1 | 
| Change in Morning Pre-dose FEV1 on Day 7 | Change from Baseline in morning pre-dose FEV1 on Day 7 | Day 7 | 
| 12 hr Post-dose Trough FEV1 on Day 7 | 12 hour post-dose trough Forced Expiratory Volume in 1 second on Day 7 | Day 7 | 
| Change From BL in Mean Morning Pre-dose Daily Peak Flow Rate on Day 7 | Change from BaseLine in mean morning pre-dose daily peak flow rate on Day 7 | Day 7 | 
| Change From BL in Mean Morning Post-dose Daily Peak Flow Rate on Day 7 | Change from BaseLine in mean morning post-dose daily peak flow rate on Day 7 | Day 7 | 
| Change From BL in Mean Evening Pre-dose Daily Peak Flow Rate on Day 7 | Change from BaseLine in mean evening pre-dose daily peak flow rate on Day 7 | Day 7 | 
| Change From BL in Mean Evening Post-dose Daily Peak Flow Rate on Day 7 | Change from BaseLine in mean evening post-dose daily peak flow rate on Day 7 | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD