Study to Assess the Efficacy and Safety of PT010 Relative to PT003 and PT009 in Subjects With Moderate to Very Severe COPD (Ethos)

Study Overview
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Brief Summary
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This is a randomized, double-blind, multi-center, parallel-group study to assess the efficacy and safety of PT010 relative to PT003 and PT009 on COPD exacerbations subjects with moderate to very severe COPD.

Detailed Description
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A randomized, double-blind, multi-center, parallel-group study to assess the efficacy and safety of PT010 relative to PT003 and PT009 on COPD exacerbations over a 52-week treatment period in subjects with moderate to very severe COPD.

Official Title
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A Randomized, Double-Blind, Multi-Center, Parallel-Group Study to Assess the Efficacy and Safety of PT010 Relative to PT003 and PT009 on COPD Exacerbations Over a 52-Week Treatment Period in Subjects With Moderate to Very Severe COPD (Ethos)

Conditions
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COPD

Intervention / Treatment
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* Drug: BGF MDI 320/14.4/9.6 μg
* Drug: GFF MDI 14.4/9.6 μg
* Drug: BGF MDI 160/14.4/9.6 μg
* Drug: BFF MDI 320/9.6 μg


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 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), 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 <65% predicted normal value calculated using NHANES III reference equations (or reference norms applicable to other regions). Subjects with history of exacerbations. 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) 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) 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 (PT010) MDI 320/14.4/9.6 μg<br>BGF MDI 320/14.4/9.6 μg, Budesonide, Glycopyrronium, Formoterol Fumarate Aerosol (PT010, BGF metered dose inhaler [MDI]) | Drug: BGF MDI 320/14.4/9.6 μg<br>* Budensonide, Glycopyrronium, and Formoterol Fumarate<br>* Other names: BGF;|
| Experimental: BGF (PT010) MDI 160/14.4/9.6 μg<br>BGF MDI 160/14.4/9.6 μg, Budesonide, Glycopyrronium, Formoterol Fumarate Aerosol (PT010, BGF metered dose inhaler [MDI]) | Drug: BGF MDI 160/14.4/9.6 μg<br>* Budensonide, Glycopyrronium, and Formoterol Fumarate<br>* Other names: BGF;|
| Experimental: BFF (PT009) MDI 320/9.6 μg<br>BFF MDI 320/9.6 μg Budesonide, Formoterol Fumarate Aerosol Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT009) | Drug: BFF MDI 320/9.6 μg<br>* Budensonide, and Formoterol Fumarate<br>* Other names: BFF;|
| Experimental: GFF (PT003) MDI 14.4/9.6 μg<br>GFF MDI 14.4/9.6 μg Glycopyrronium, Formoterol Fumarate Aerosol Budesonide and Formoterol Fumarate Inhalation Aerosol (PT003) | Drug: GFF MDI 14.4/9.6 μg<br>* Glycopyrronium, and Formoterol Fumarate<br>* Other names: GFF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Rate of Moderate or Severe Exacerbations | Adjusted Rate of Moderate or Severe Exacerbations | 52-week treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Moderate or Severe COPD Exacerbation | Time to first moderate or severe COPD exacerbation (proportion with event reported as median time was not reached, statistical analyses are based upon time to event) | 52 Weeks | 
| Change From Baseline in Average Daily Rescue Ventolin HFA Use Over 24 Weeks | Change from baseline in average daily rescue Ventolin HFA use over 24 weeks | 24 Weeks | 
| Percentage of Subjects Achieving a MCID of 4 Units or More in SGRQ Total Score | Percentage of subjects achieving a minimal clinically important difference (MCID) of 4 units or more in SGRQ (St. George's Respiratory Questionnaire) total score at Week 24 | at Week 24 | 
| Time to Death (All Cause) | Subject Deaths (all cause) | 52 Weeks | 
| Rate of Severe COPD Exacerbations | Rate of severe COPD exacerbations | 52 Weeks |