A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® (Kronos)

Study Overview
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Brief Summary
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Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® in Subjects with Moderate to Very Severe Chronic Obstructive Pulmonary Disease.

Detailed Description
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A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® as an Active Control in Subjects with Moderate to Very Severe Chronic Obstructive Pulmonary Disease This study includes the following 3 sub-studies: 12-hour Pulmonary Function Test (PFT), Pharmacokinetic (PK) Profile, and Hypothalamic-pituitary-adrenal Axis.

Official Title
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A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® as an Active Control in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease

Conditions
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COPD

Intervention / Treatment
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* Drug: BGF MDI 320/14.4/9.6 μg
* Drug: GFF MDI (PT003) 14.4/9.6 μg
* Drug: BFF MDI (PT009) 320/9.6 μg
* Drug: Symbicort® Turbuhaler® (TBH) Inhalation Powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Given their signed written informed consent to participate. 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 serum pregnancy test at Visit 1, and agrees to acceptable contraceptive methods used consistently and correctly for the duration of the study. Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS), or other local applicable guidelines. Current or former smokers with a history of at least 10 pack-years of cigarette smoking. Forced expiratory volume in 1 second (FEV1)/Forced vital capacity (FVC) ratio must be <0.70 and FEV1 must be <80% predicted normal value calculated using NHANES III reference equations (or reference norms applicable to other regions). Required COPD maintenance therapy: All Subjects must have been on two or more inhaled maintenance therapies for the management of their COPD for at least 6 weeks prior to Screening. Scheduled SABA and/or scheduled SAMA are considered inhaled maintenance therapies Please refer to the study protocol for the complete inclusion criteria list. Exclusion Criteria Significant diseases or conditions other than COPD, 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 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 Visit 1 (Screening) or during the Screening Period Immune suppression or severe neurological disorders affecting control of the upper airway or other risk factors that in the opinion of the Investigator would put the subject at substantial risk of pneumonia. Subjects with a diagnosis of narrow angle glaucoma, who, in the opinion of the Investigator, have not been adequately treated. Subjects who have a history of hypersensitivity to β2-agonists, budesonide or any other corticosteroid components, glycopyrronium or other muscarinic anticholinergics, or any other component of the IMPs. 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BGF MDI (PT010) 320/14.4/9.6 μg ex-actuator<br>BGF MDI 320/14.4/9.6 μg,Budesonide, Glycopyrronium, Formoterol Fumarate Inhalation Aerosol | Drug: BGF MDI 320/14.4/9.6 μg<br>* Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])<br>* Other names: BGF;|
| Experimental: GFF MDI (PT003) 14.4/9.6 μg ex-actuator<br>GFF MDI 14.4/9.6 μg ex-actuator Glycopyrronium, Formoterol Fumarate Inhalation Aerosol | Drug: GFF MDI (PT003) 14.4/9.6 μg<br>* Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)<br>* Other names: GFF;|
| Experimental: BFF MDI (PT009) 320/9.6 μg ex-actuator<br>BFF MDI 320/9.6 μg, Budesonide, Formoterol Fumarate Inhalation Aerosol | Drug: BFF MDI (PT009) 320/9.6 μg<br>* Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)<br>* Other names: BFF;|
| Active Comparator: Symbicort<br>Symbicort® Turbuhaler® (TBH) Inhalation Powder 200/6 μg | Drug: Symbicort® Turbuhaler® (TBH) Inhalation Powder<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 AUC0-4 | FEV1 AUC0-4 (L) for The Efficacy Estimand (Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 4 hours (AUC0-4) AUC was normalized for length of follow up (e.g. typically 4 hours)). | at Week 24 | 
| Change From Baseline in Morning Pre-dose Trough FEV1 | Morning Pre-Dose Trough FEV1 (L) for The Efficacy Estimand | at Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Morning Pre-dose Trough FEV1 | Morning Pre-Dose Trough FEV1 (L) for The Efficacy Estimand | over 24 Weeks | 
| Peak Change From Baseline in FEV1 Within 4 Hours Post-dosing | Peak Change from Baseline in FEV1 (L) Within 4 Hours Post-Dose for The Efficacy Estimand | at Week 24 | 
| Rate of Moderate or Severe COPD Exacerbations | Rate of Moderate or Severe COPD Exacerbations for the Efficacy Estimand | over 24 weeks | 
| Percentage of Subjects Achieving a Minimal Clinically Important Difference (MCID) of 4 Units or More in SGRQ Total Score (SGRQ Responders) | Change from BGF | at Week 24 | 
| Change From Baseline in Average Daily Rescue Ventolin HFA Use | Change from Baseline in Mean Daily Number of Puffs of Rescue Ventolin HFA for The Efficacy Estimand | over 24 Weeks | 
| Time to Onset of Action on Day 1, 5 Minutes Post Dose | FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand | Day 1 | 
| Time to Onset of Action on Day 1, 15 Minutes Post Dose | FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand | Day 1 | 
| Time to Onset of Action on Day 1, 30 Minutes Post Dose | FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand | Day 1 | 
| Time to Onset of Action on Day 1, 1 Hour Post Dose | FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand | Day 1 | 
| Time to Onset of Action on Day 1, 2 Hours Post Dose | FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand | Day 1 | 
| Time to Onset of Action on Day 1, 4 Hours Post Dose | FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand | Day 1 |