PT003 MDI Dose Confirmation Study

Study Overview
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Brief Summary
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The primary objective of this study is to demonstrate efficacy of PT003 MDI relative to its individual components (PT001 MDI and PT005 MDI) in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Official Title
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A Randomized, Double Blind, Chronic Dosing (7 Days), Two Period, Six Treatment, Incomplete Block, Cross Over, Multi Center Study to Assess Efficacy and Safety of Four Doses of PT003 MDI in Patients With Moderate to Severe COPD, Compared With Its Individual Components (PT005 MDI and PT001 MDI) as Active Controls

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: PT003
* Drug: PT001
* Drug: PT005


Participation Criteria
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Eligibility Criteria
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Key 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 Key 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 inclusion/exclusion criteria as defined in the protocol

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PT003 (Dose 1)<br>PT003 MDI Dose 1 | Drug: PT003<br>* PT003 MDI administered as two puffs BID for 7 days<br>|
| Experimental: PT003 (Dose 2)<br>PT003 MDI Dose 2 | Drug: PT003<br>* PT003 MDI administered as two puffs BID for 7 days<br>|
| Experimental: PT003 (Dose 3)<br>PT003 MDI Dose 3 | Drug: PT003<br>* PT003 MDI administered as two puffs BID for 7 days<br>|
| Experimental: PT003 (Dose 4)<br>PT003 MDI Dose 4 | Drug: PT003<br>* PT003 MDI administered as two puffs BID for 7 days<br>|
| Experimental: PT001<br>PT001 MDI | Drug: PT001<br>* PT001 MDI administered as two puffs BID for 7 days<br>|
| Experimental: PT005<br>PT005 MDI | Drug: PT005<br>* PT005 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 AUC0-12 | Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 relative to baseline following chronic dosing (1 week). | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Change From Baseline in FEV1 | Peak change from baseline in FEV1 through 2 hours | Day 1 | 
| Time to Onset of Action | At least 10% improvement in mean FEV1 | Day 1 | 
| At Least 12% Improvement in FEV1 | Proportion of subjects achieving >=12% improvement in FEV1 relative to baseline | Day 1 | 
| Peak Change in IC | Mean inspiratory capacity (IC) of 1 and 2 hours post-dose minus baseline | Day 1 | 
| Morning Pre-dose FEV1 | Change from baseline in morning pre-dose FEV1 (average of 60- and 30-minute pre-dose values on Day 7) | Day 7 | 
| FEV1 Through 6 Hours | Peak change from baseline in FEV1 through 6 hours | Day 7 | 
| Peak Change From Baseline in IC | Peak change from baseline in inspiratory capacity (IC) (mean of 1 and 2 hours post-dose minus baseline) | Day 7 | 
| Mean Evening Trough FEV1 | Change from baseline in mean evening 12-hour post-dose trough FEV1 | Day 7 | 

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