A Study to Assess the Effects of PT003 and Placebo MDI on Specific Image Based Airway Volumes and Resistance in Subjects With Moderate to Severe COPD

Study Overview
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Brief Summary
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Study to Evaluate the Effects of PT003 and Placebo MDI on Specific Image Based Airway Volumes and Resistance With Moderate to Severe COPD.

Detailed Description
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Enrolled patients with COPD who were randomized to receive either PT003 MDI or Placebo MDI first and then crossed over to receive the opposite intervention. The study consisted of 2 treatment periods of 14 days separated by a washout period of 5-21 days.

Official Title
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A Randomized, Double-Blind, Two Treatment, Two Period, Chronic Dosing (2 Weeks), Cross-Over, Single-Center Study to Evaluate the Effects of PT003 and Placebo MDI on Specific Image Based Airway Volumes and Resistance in Subjects With Moderate to Severe COPD

Conditions
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COPD

Intervention / Treatment
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* Drug: GFF MDI (PT003) 14.4/9.6μg
* Drug: Placebo MDI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-child bearing potential (ie, physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal); or Child bearing potential, has a negative urine pregnancy test at Visit 1 and agrees to an acceptable method of contraception 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. At Visit 1, FEV1/FVC ratio must be <0.70 At Visit 1, post-bronchodilator FEV1/FVC ratio of <70% and FEV1 must be 30% to 80% before predicted normal value, calculated using NHANES III reference equations. 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, or are planning to become pregnant during the course of the study, or women of childbearing potential who are not using an acceptable method of contraception. 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 Visit 1 (Screening) or during the run-in period (Visit 1 to Visit 2). 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 Visit 1 (Screening) or during the run-in period (Visit 1 to Visit 2). Subjects with a diagnosis of angle closure glaucoma will be excluded, regardless of whether or not they have been treated. Subjects who have a history of hypersensitivity to β2-agonists, glycopyrronium or other muscarinic anticholinergics, or any component of the MDI. Please refer to the study protocol for the complete inclusion criteria list.

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, 14.4/9.6μg<br>Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI) | Drug: GFF MDI (PT003) 14.4/9.6μg<br>* Glycopyrronium and Formoterol Fumarate<br>* Other names: GFF;|
| Placebo Comparator: Placebo MDI<br>Placebo Metered Dose Inhaler (MDI) | Drug: Placebo MDI<br>* Comparator: Placebo MDI which contains no active ingredients<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specific Airway Volume (siVaw) | Specific image-based airway volume. Average across lobe, adjusted for lobe volume | Day 15 | 
| Specific Airway Resistance (siRaw) | Specific image-based airway resistance. Average across lobes, adjusted for lobe volume | Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Airway Resistance (iRaw) | iRaw represents the airway resistance, averaged across lobes, without correction for lung lobe volume | Day 15 | 
| Airway Volume (iVaw) | iVaw represents the airway Volume, averaged across lobes, without correction for lung lobe volume | Day 15 | 
| Change From Baseline in FEV1 (L) at Day 15 | Change from baseline in Forced Expiratory Volume at 1 second | Baseline and Day 15 | 
| Change From Baseline in FRC (L) at Day 15 | Change from baseline in Functional Residual Capacity | Baseline and Day 15 |