24-hour Lung Function in Subjects With Moderate to Very Severe COPD After Treatment With PT003, Open-Label Spiriva® Respimat® as an Active Control, and Placebo

Study Overview
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Brief Summary
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Randomized, Phase IIIb, Three-period, Three-treatment, Double-blind, Multi-center, Crossover Study to Evaluate the 24-hour Lung Function Profile in Subjects with Moderate to Very Severe COPD after 4 Weeks of Treatment with PT003, Open-Label Spiriva® Respimat® (Tiotropium Bromide) as an Active Control, and Placebo.

Official Title
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A Randomized, Phase IIIb, Three-period, Three-treatment, Double-blind, Multi-center, Crossover Study to Evaluate the 24-hour Lung Function Profile in Subjects With Moderate to Very Severe COPD After 4 Weeks of Treatment With PT003, Open-Label Spiriva® Respimat® (Tiotropium Bromide) as an Active Control, and Placebo

Conditions
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COPD

Intervention / Treatment
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* Drug: GFF MDI (PT003)
* Drug: Placebo MDI
* Drug: Spiriva® Respimat® (Tiotropium Bromide)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 40 years of age and no older than 80 at Screening Women of non-child bearing potential or negative serum pregnancy test at Screening, and agrees to acceptable contraceptive methods used consistently and correctly Screening until 14 days after final visit. Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) Current or former smokers with a history of at least 10 pack-years of cigarette smoking Pre- and post-bronchodilator FEV1/FVC ratio of <0.70 Post-bronchodilator FEV1 must be <80% predicted normal value, calculated using NHANES III reference equations, and the measured FEV1 must also be ≥750 mL if FEV1 <30% of predicted normal value. Exclusion Criteria: Significant diseases other than COPD, i.e., disease or condition which, in the opinion of the Investigator, may put the subject at risk because of participation in the study or may influence either the results of the study or the subject's ability to participate in the study. Women who are pregnant or lactating. Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma. Subjects who have been hospitalized due to poorly controlled COPD within 3 months prior to Screening or during the Screening Period. Subjects who have poorly controlled COPD, defined as acute worsening of COPD that requires treatment with oral corticosteroids or antibiotics within 6 weeks prior to Screening or during the Screening Period. Subjects who have clinically significant uncontrolled hypertension. Subjects who have cancer that has not been in complete remission for at least five years. Subjects with abnormal liver function tests defined as AST, ALT, or total bilirubin ≥1.5 times upper limit of normal at Screening and on repeat testing. Subjects with a diagnosis of angle closure glaucoma will be excluded, regardless of whether or not they have been treated. Subjects with a diagnosis of open angle glaucoma who have intraocular pressure controlled with medication(s) are eligible. Subjects with symptomatic prostatic hypertrophy that is clinically significant in the opinion of the Investigator. Subjects with a trans-urethral resection of prostate (TURP) or full resection of the prostate within 6 months prior to Screening are excluded from the study. Subjects with bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator.

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: GFF MDI (PT003)<br>Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI) | Drug: GFF MDI (PT003)<br> <br> * Other names: Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI);|
| Placebo Comparator: Placebo MDI<br>Placebo Metered Dose Inhaler (MDI) for Glycopyrronium and Formoterol Fumarate Inhalation Aerosol | Drug: Placebo MDI<br> <br> * Other names: Placebo Metered Dose Inhaler (MDI) for Glycopyrronium and Formoterol Fumarate Inhalation Aerosol;|
| Active Comparator: Spiriva® Respimat® (Tiotropium Bromide)<br>Tiotropium Bromide Inhalation Solution; Spiriva® Respimat® (Spiriva) | Drug: Spiriva® Respimat® (Tiotropium Bromide)<br>* Tiotropium Bromide Inhalation Solution; Spiriva® Respimat® (Spiriva)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-24 | Normalized Forced Expiratory Volume in 1 second (FEV1) Area Under the Curve (AUC) 0-24 | Pre dose, 15 and 30 minutes, 1, 2, 4, 8, 12, 12.25, 12.5, 13, 14, 16, 22, and 24 hours post the morning dose on Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 AUC12-24 | Normalized FEV1 AUC12-24 | Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the evening dose on Day 29 | 
| FEV1 AUC0-12 | Normalized FEV1 AUC0-12 | Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the morning dose on Day 29 | 
| Peak Change From Baseline in FEV1 Evening | Peak Change From Baseline in FEV1 Evening | Baseline and Day 29 | 
| Peak Change From Baseline in FEV1 Morning | Peak Change From Baseline in FEV1 Morning | Baseline and Day 29 | 
| Morning Pre-Dose Trough FEV1 on Day 29 | Morning Pre-Dose Trough FEV1 on Day 29 | Day 29 | 
| Morning Pre-Dose Trough FEV1 on Day 30 | Morning Pre-Dose Trough FEV1 on Day 30 | Day 30 | 
| Peak Change From Baseline in IC (Inspiratory Capacity) Evening | Peak Change From Baseline in IC Evening | Baseline and Day 29 | 
| Peak Change From Baseline in IC Morning | Peak Change From Baseline in IC Morning | Baseline and Day 29 |