Efficacy and Safety Study of PT009, PT008, and PT005 in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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This is a Phase IIb, randomized, double blind, chronic dosing (28 days), four period, five treatment, incomplete block, crossover design in subjects with moderate to severe COPD. The overall objective is to demonstrate that the combination of budesonide (BD; PT008) and formoterol fumarate (FF; PT005) in a metered-dose inhaler (MDI); (BFF MDI; PT009) provides benefit on lung function compared with BD MDI in subjects with moderate to severe COPD.

Official Title
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A Randomized, Double Blind, Chronic Dosing (28 Days), Four Period, Five Treatment, Incomplete Block, Multi Center, Crossover Study to Assess the Efficacy and Safety of PT009, PT008, and PT005 in Subjects With Moderate to Severe COPD

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: BFF MDI 320/9.6 μg
* Drug: BFF MDI 160/9.6 μg
* Drug: BFF MDI 80/9.6 μg
* Drug: BD MDI 320 μg
* Drug: FF MDI 9.6 μg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent Form (ICF) prior to any study related procedures COPD Diagnosis: Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) Tobacco Use: Current or former smokers with a history of at least 10 pack years of cigarette smoking Women of non-childbearing potential or medically acceptable contraception for women of child-bearing potential and males with female partners of childbearing potential Severity of Disease: Subjects with an established clinical history of COPD and severity defined as: FEV1/forced vital capacity (FVC) ratio of <0.70; At Screening (Visit 1a/b), post bronchodilator FEV1 must be <80% predicted normal value, calculated using NHANES III (Third National Health and Nutrition Examination Survey) reference equations; the measured FEV1 must also be ≥30% of predicted normal value; at Visit 2, the average of the 60 minutes and 30 minutes pre dose FEV1 assessments must be <80% predicted normal value calculated using NHANES III reference equations Screening clinical laboratory tests must be acceptable to the Investigator Screening ECG must be acceptable to the Investigator Chest x ray or computerized tomography (CT) scan within 6 months prior to Visit 1a must be acceptable to the Investigator. Exclusion Criteria: Significant diseases other than COPD, ie., 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 Pregnancy, nursing female subjects, or subjects trying to conceive, or not using medically acceptable form of contraception Asthma: Subjects who have a primary diagnosis of asthma (Note: Subjects with a prior history of asthma are eligible if COPD is currently their primary diagnosis). Alpha 1 Antitrypsin Deficiency: Subjects who have alpha 1 antitrypsin deficiency as the cause of COPD -Active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung disease, and uncontrolled sleep apnea (ie., in the opinion of the Investigator severity of the disorder would impact the conduct of the study)- Clinically significant neurologic, cardiovascular, hepatic, renal, endocrinologic, pulmonary, hematological, psychiatric, or other medical illness that would interfere with participation in this study Poorly Controlled COPD History of ECG abnormalities Cancer not in complete remission for at least 5 years Clinically significant, symptomatic prostatic hypertrophy Male subjects with a trans-urethral resection of the prostate or full resection of the prostate within 6 months prior to Screening Clinically significant bladder neck obstruction or urinary retention Inadequately treated glaucoma History of an allergic reaction or hypersensitivity to any drug or to any component of the formulations used in this study

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BFF MDI 320/9.6 μg<br>Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 320/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID) | Drug: BFF MDI 320/9.6 μg<br>* Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 320/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)<br>|
| Experimental: BFF MDI 160/9.6 μg<br>Budesonide and formoterol fumarate metered dose inhaler (BFF MDI)160/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID) | Drug: BFF MDI 160/9.6 μg<br>* Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 160/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)<br>|
| Experimental: BFF MDI 80/9.6 μg<br>Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 80/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID) | Drug: BFF MDI 80/9.6 μg<br>* Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 80/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)<br>|
| Experimental: BD MDI 320 μg<br>Budesonide metered dose inhaler (BD MDI) 320 μg; PT008 administered as 2 inhalations, twice daily (BID) | Drug: BD MDI 320 μg<br>* Budesonide metered dose inhaler (BD MDI) 320 μg; PT008 administered as 2 inhalations, twice daily (BID)<br>|
| Experimental: FF MDI 9.6 μg<br>Formoterol fumarate metered dose inhaler (FF MDI) 9.6 μg; PT005 administered as 2 inhalations, twice daily (BID) | Drug: FF MDI 9.6 μg<br>* Formoterol fumarate metered dose inhaler (FF MDI) 9.6 μg; PT005 administered as 2 inhalations, twice daily (BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 AUC0-12 on Day 29 | Change from Baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC0-12) | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Morning Pre-dose Trough FEV1 Over 28 Days |  | Over 28 days | 
| Peak Change From Baseline in FEV1 (in Liters) Day 15 |  | Day 15 | 
| Peak Change From Baseline in FEV1 (in Liters) Day 29 |  | Day 29 | 
| Peak Change From Baseline in FEV1 on Day 1 |  | Day 1 | 
| Forced Vital Capacity (FVC) AUC0-12 on Day 29 |  | Day 29 | 
| Transition Dyspnea Index (TDI) Focal Score on Day 29 | Min/Max Range of TDI scale -9 (major deterioration) to +9 (major improvement) | Day 29 | 
| Change From Baseline in Average Daily Use of Rescue Ventolin HFA Over the Last Week of Treatment |  | Visit 12-13 (7 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Budesonide and formoterol inhalation aerosol