PT001 MDI Versus Spiriva® in Patients With Moderate to Severe 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 assess efficacy relative to placebo of GP MDI in subjects with moderate to severe chronic obstructive pulmonary disease (COPD) within the range of doses evaluated in this protocol. To this end, each dose of GP 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 (Test Products and Placebo), Chronic Dosing (14 Days), Four Period, Eight Treatment, Placebo-Controlled, Incomplete Block, Cross Over, Multi Center Study to Assess Efficacy and Safety of Six Doses of PT001 in Patients With Moderate to Severe COPD, Compared With Spiriva® Handihaler® (Tiotropium Bromide, 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: Tiotropium Bromide
* Drug: PT001 Placebo 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 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> | Drug: PT001 MDI<br>* Administered as two puffs BID for 14 days<br>|
| Experimental: PT001 MDI (Dose 2)<br> | Drug: PT001 MDI<br>* Administered as two puffs BID for 14 days<br>|
| Experimental: PT001 MDI (Dose 3)<br> | Drug: PT001 MDI<br>* Administered as two puffs BID for 14 days<br>|
| Experimental: PT001 MDI (Dose 4)<br> | Drug: PT001 MDI<br>* Administered as two puffs BID for 14 days<br>|
| Experimental: PT001 MDI (Dose 5)<br> | Drug: PT001 MDI<br>* Administered as two puffs BID for 14 days<br>|
| Experimental: PT001 MDI (Dose 6)<br> | Drug: PT001 MDI<br>* Administered as two puffs BID for 14 days<br>|
| Placebo Comparator: PT001 Placebo MDI<br> | Drug: PT001 Placebo MDI<br> <br> |
| Active Comparator: Spiriva® Handihaler® (Tiotropium Bromide)<br> | Drug: Tiotropium Bromide<br>* Taken as 1 capsule containing 18 µg of tiotropium via the Handihaler DPI<br>* Other names: Spiriva® Handihaler®;|

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 1 second (FEV1) normalized area under the curve 0-12 hours (AUC0-12) following chronic dosing for 14 days. | Day 14 (-1 hr, -30 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 hr, 11.5 hr, 12 hr) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Change From Baseline in FEV1 | Highest value of FEV1 post dose on day 1 | Day 1 | 
| Time to Onset of Action (>10% Improvement in FEV1) on Day 1 | Time to Onset of Action (>10% Improvement in FEV1) on Day 1. | Day 1 (15 min, 30 min, 1 hr, 2 hrs, no onset within 2 hrs) | 
| Percentage of Subjects Achieving at Least 12% Improvement in FEV1 | Percentage of subjects achieving at least 12% improvement in FEV1. | Day 1 | 
| Peak Change From Baseline in Inspiratory Capacity (IC) | Peak change in Inspiratory Capacity (IC) mean of 1 and 2 hour post-dose assessments minus the baseline | Day 1 (1 hr and 2 hr post-dose ) | 
| Change From Baseline in Morning Pre-dose Trough FEV1 | Change from baseline in morning pre-dose trough FEV1 (average of the 60 and 30-minute pre-dose values on Treatment Day 7 minus the baseline) | Day 7 (average of the 60 and 30-minute pre-dose values on Treatment Day 7 minus the baseline) | 
| Peak Change From Baseline in FEV1 | Peak change from baseline in FEV1 (defined as the change at the highest value of FEV1 post-dose minus the baseline) | Day 7 | 
| Change From Baseline in Morning Pre-dose Trough Inspiratory Capacity (IC) | Change from baseline in morning pre-dose trough IC (average of the 60 and 30-minute pre-dose assessments minus the baseline) | Day 7 | 
| Peak Change From Baseline in IC | Peak change from baseline in IC (mean of 1 hr and 2 hr post-dose assessments) | Day 7 (mean of 1 hr and 2 hr post-dose assessments) | 
| Change From Baseline in Mean Morning Pre-dose Daily PEFR | Change from baseline in mean morning pre-dose daily PEFR (peak expiratory flow rate) taken by subjects and recorded in subject diaries, up through Diary Day 7 of each treatment period (excluding reading taken pre-dose on Visit 2 [Treatment Day 1]) | Day 7 (60 minutes pre-dose, 30 minutes pre-dose) | 
| Change From Baseline in Morning Post-dose Daily PEFR | Change from baseline in morning post-dose daily PEFR (peak expiratory flow rate) taken by subjects and recorded in subject diaries, up through Diary Day 7 of each treatment period (excluding reading taken pre-dose on Visit 2 [Treatment Day 1]) | Day 7 (30 minutes post-dose) | 
| Change From Baseline in Mean Evening Pre-dose PEFR | Change from baseline in mean evening pre-dose daily peak flow readings taken by subjects and recorded in subject diaries, up through Diary Day 7 of each treatment period (subjects taking Spiriva performed a single evening assessment) | Day 7 | 
| Change From Baseline in Mean Evening Post-dose PEFR | Change from baseline in mean evening post-dose daily peak flow readings taken by subjects and recorded in subject diaries, up through Diary Day 7 of each treatment period (subjects taking Spiriva performed a single evening assessment) | Day 7 | 
| Mean Number of Puffs of Rescue Medication | Mean number of puffs of rescue medication recorded in subject diaries during each treatment period and by treatment and numbers of days treated | Day 7 | 
| Change From Baseline in Morning Pre-dose Trough FEV1 | Change from baseline in morning pre-dose trough FEV1 (average of the 60 and 30-minute pre-dose values on Treatment Day 14 minus the baseline) | Day 14 (average of the 60 and 30-minute pre-dose values on Treatment Day 14 minus the baseline) | 
| Peak Change From Baseline in FEV1 | Peak change from baseline in FEV1 (defined as the change at the highest value of FEV1 post-dose minus the baseline) | Day 14 | 
| Change From Baseline for Mean Morning Pre-dose Trough IC | Change from baseline for mean morning pre-dose trough IC (average of the 60 and 30-minute pre-dose assessments minus the baseline) | Day 14 (average of the 60 and 30-minute pre-dose assessments minus the baseline) | 
| Peak Change From Baseline in IC | Peak change from baseline in IC (mean of 1 and 2 hour post-dose assessments minus the baseline) | Day 14 (mean of 1 and 2 hour post-dose assessments minus the baseline) | 
| Change From Baseline in 12-hour Post-dose Trough FEV1 | 12-hour post-dose trough FEV1 was defined as the mean of the FEV1 assessments taken at 11.5 and 12 hours post-dose minus the baseline | Day 14 (Baseline, 11.5 and 12 hours post dose) | 
| Change From Baseline in Mean Morning Pre-dose Daily PEFR | Change from baseline in mean morning pre-dose daily peak flow readings taken by subjects and recorded in subject diaries during each treatment period for subjects with more than 7 days of diary data (mean reading excluded reading taken pre-dose on Visit 2 [Treatment 1 Day 1] | Baseline, Treatment Day 1 and every day, to the end of the 14-Day Treatment period before dosing, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7) | 
| Change From Baseline in Mean Morning Post-dose Daily PEFR | Change from baseline in mean morning post-dose daily peak flow readings taken by subjects and recorded in subject diaries during each treatment period for subjects with more than 7 days of diary data (mean reading excluded reading taken pre-dose on Visit 2 [Treatment 1 Day 1] | Baseline, Treatment Day 1 and every day, to the end of the 14-Day Treatment period 30 minutes post dosing, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7) | 
| Change From Baseline in Mean Evening Pre-dose Daily PEFR | Change from baseline in mean evening pre-dose daily peak flow readings taken by subjects and recorded in subject diaries during each treatment period for subjects with more than 7 days of diary data (subjects taking Spiriva performed a single evening assessment) | Treatment Day 1 to the end of the 14-Day Treatment, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7) | 
| Change From Baseline in Mean Evening Post-dose Daily PEFR | Change from baseline in mean evening post-dose daily peak flow readings taken by subjects and recorded in subject diaries during each treatment period for subjects with more than 7 days of diary data (subjects taking Spiriva performed a single evening assessment) | Through the end of the 14-Day Treatment | 
| Mean Number of Puffs of Rescue Medication (End of Treatment) | Mean number of puffs of rescue medication recorded in subject diaries during each treatment period and by treatment and numbers of days treated | Day 14 (End of treatment) | 
| Change From Baseline in Morning Pre-dose Trough FEV1 (mL) Averaging Treatment Day 7 and Day 14 | Change from Baseline in Morning Pre-dose Trough FEV1 (mL) Averaging Treatment Day 7 and Day 14 | Day 1 through Day 14 | 

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