PT001 MDI Versus Atrovent Study in Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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The overall objective of this study is to determine an optimal dose and dosing regimen of PT001 MDI for further evaluation in later stage studies.

Detailed Description
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The primary objective of this study is to demonstrate efficacy relative to placebo of PT001 MDI in patients with moderate to severe chronic obstructive pulmonary disease (COPD) within the range of doses evaluated in this protocol. To this end, each dose of PT001 MDI will be compared to placebo with respect to the primary efficacy endpoint, FEV1 AUC0-12 relative to baseline.

Official Title
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A Randomized, Double-Blind, Chronic Dosing (7 Days), Three-Period, Six-Treatment, Placebo-Controlled, Incomplete Block, Cross-Over, Multi-Center Study to Assess Efficacy and Safety of Four Doses of PT001 in Patients With Moderate to Severe COPD, Compared With Atrovent® HFA Inhalation Aerosol (Open-Label) as An Active Control

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: PT001 MDI
* Drug: Ipratropium Bromide HFA Inhalation Aerosol
* Other: Placebo MDI


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: PT001 MDI (Dose 1)<br>PT001 MDI | Drug: PT001 MDI<br>* PT001 MDI administered as two puffs BID for 7 days<br>|
| Experimental: PT001 MDI (Dose 2)<br>PT001 MDI | Drug: PT001 MDI<br>* PT001 MDI administered as two puffs BID for 7 days<br>|
| Experimental: PT001 MDI (Dose 3)<br>PT001 MDI | Drug: PT001 MDI<br>* PT001 MDI administered as two puffs BID for 7 days<br>|
| Experimental: PT001 MDI (Dose 4)<br>PT001 MDI | Drug: PT001 MDI<br>* PT001 MDI administered as two puffs BID for 7 days<br>|
| Active Comparator: Ipratropium Bromide HFA Inhalation Aerosol<br>Ipratropium Bromide HFA Inhalation Aerosol | Drug: Ipratropium Bromide HFA Inhalation Aerosol<br>* Taken as 2 inhalations of the 17 µg per actuation strength MDI QID<br>* Other names: Atrovent;|
| Placebo Comparator: Placebo MDI<br>PT001 Placebo MDI | Other: Placebo MDI<br>* Matching placebo to 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 AUC0-12 | FEV1 AUC0-12 following chronic dosing (1 week), normalized. | Day 7 ( -1 hour, -30 min, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 5.5 hours, 6.5 hours, 8 hours, 10 hours, 11.5 hours, and 12 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Change From Baseline in FEV1 on Day 1 | Highest value of FEV1 post-dose minus baseline on Day 1 (baseline-adjusted) | Day 1 | 
| Time to Onset of Action ( ≥10% Improvement in FEV1) on Day 1 | Time to onset of action ( ≥10% improvement in FEV1) | Day 1 (15 min, 30 min, 1 hour, 2 hours) | 
| Proportion of Subjects Achieving at Least 12% Improvement in FEV1 on Day 1 | Proportion of subjects achieving at least 12% improvement in FEV1 (relative to baseline) | Day 1 | 
| Peak Change From Baseline in IC on Day 1 | Peak change from baseline in Inspiratory Capacity (IC) on Day 1 (mean of 1 and 2 hours post-dose minus baseline on Day 1) | Day 1 | 
| Change From Baseline in Morning Pre-dose FEV1 on Day 7 | Change from baseline in morning pre-dose FEV1 | Day 7 | 
| Peak Change From Baseline in FEV1 on Day 7 | Peak change from baseline in FEV1 | Day 7 | 
| Peak Change From Baseline in IC on Day 7 | Peak change from baseline in IC | Day 7 | 
| Change From Baseline in 12-hour Post-dose Trough FEV1 on Day 7 | Change from baseline in 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