Study to Assess Efficacy and Safety of PT009 Compared to PT005, PT008, and Symbicort® Turbuhaler® on Lung Function Over 24-Weeks in Subjects With Moderate to Very Severe COPD

Study Overview
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Brief Summary
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This is a Phase III randomized, double-blind, parallel group, multi-center, 24-week lung function study with BFF MDI (320/9.6 μg and 160/9.6 μg) compared to FF MDI 9.6 μg, BD MDI 320 μg, and open-label Symbicort® TBH (200/6 μg) administered BID.

Detailed Description
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This is a Phase III randomized, double-blind, parallel group, multi-center, 24-week lung function study with BFF MDI (320/9.6 μg and 160/9.6 μg) compared to FF MDI 9.6 μg, BD MDI 320 μg, and open-label Symbicort® TBH (200/6 μg) administered BID. Subjects will undergo a 1- to 4-week Screening Period. Subjects who successfully complete the Screening Period will be to one of the following five treatment groups:BFF MDI 320/9.6 μg BID (N=660), BFF MDI 160/9.6 μg BID, FF MDI 9.6 μg BID, BD MDI 320 μg BID, Symbicort®, TBH 400/12 μg BID. Following randomization, subjects will enter the Treatment Period and undergo additional treatment visits over 24 weeks.

Official Title
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A Randomized, Double-Blind, Parallel Group, Multi-Center Study to Assess the Efficacy and Safety of PT009 Compared to PT005, PT008, and Open-label Symbicort® Turbuhaler®, as an Active Control, on Lung Function Over a 24-Week Treatment Period in Subjects With Moderate to Very Severe COPD

Conditions
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Chronic Obstructive Pulmonary Disorder

Intervention / Treatment
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* Drug: BFF MDI 320/9.6 μg
* Drug: BFF MDI 160/9.6 μg
* Drug: FF MDI 9.6 μg
* Drug: BD MDI 320 μg
* Drug: Symbicort® TBH 400/12 μg BID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Give their signed written informed consent to participate Are at least 40 years of age and no older than 80 years COPD patients who are symptomatic Must be receiving one or more inhaled bronchodilators as maintenance therapy Exclusion Criteria: Current diagnosis of asthma, COPD due to α1-Antitrypsin Deficiency Known active tuberculosis, lung cancer, cystic fibrosis, significant bronchiectasis, Pulmonary resection or Lung Volume Reduction Surgery during the past 6 months Long-term-oxygen therapy (≥ 12 hours a day).

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: BFF MDI 320/9.6 μg<br>Budesonide and Formoterol Fumarate Inhalation Aerosol 160/4.8 μg per actuation MDI/120 inhalations Taken as 2 inhalations BID | Drug: BFF MDI 320/9.6 μg<br>* Blinded Treatment<br>* Other names: Budesonide and Formoterol Fumarate Inhalation Aerosol;|
| Experimental: BFF MDI 160/9.6 μg<br>Budesonide and Formoterol Fumarate Inhalation Aerosol-80/4.8 μg per actuation MDI/120 inhalations Taken as 2 inhalations BID | Drug: BFF MDI 160/9.6 μg<br>* Blinded Treatment<br>* Other names: Budesonide and Formoterol Fumarate Inhalation Aerosol;|
| Experimental: FF MDI 9.6 μg<br>Formoterol Fumarate Inhalation Aerosol-4.8 μg per actuation MDI/ 120 inhalations Taken as 2 inhalations BID | Drug: FF MDI 9.6 μg<br>* Blinded Treatment<br>* Other names: Formoterol Fumarate Inhalation Aerosol;|
| Experimental: BD MDI 320 μg<br>Budesonide inhalation Aerosol 160 μg per actuation MDI/120 inhalations Taken as 2 inhalations BID | Drug: BD MDI 320 μg<br>* Blinded Treatment<br>* Other names: Budesonide Inhalation Aerosol;|
| Other: Symbicort® TBH 400/12 μg<br>Symbicort Turbuhaler 400/12 μg Taken as 2 inhalations BID | Drug: Symbicort® TBH 400/12 μg BID<br>* Open Label<br>* Other names: Symbicort® Turbuhaler;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 (BFF MDI Versus FF MDI) | Change from baseline in morning pre-dose trough FEV1 (Forced expiratory volume in 1 second) at Week 24 (BFF MDI versus FF MDI) | at Week 24 | 
| Change From Baseline in FEV1 AUC0-4 (BFF MDI vs BD MDI) | Changes from baseline in FEV1 AUC0-4 were normalized by taking the area under the curve value and dividing by the length of time under consideration (usually 4 hours). This normalization represents a weighted average of the change from baseline in FEV1 over the 4-hour period. | at Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Moderate or Severe COPD Exacerbation (BFF MDI vs FF MDI). | Time to first moderate or severe COPD (Chronic Obstructive Pulmonary Disease) exacerbation (BFF MDI vs FF MDI). | over 24 Weeks (timepoints of 4, 12 & 20 weeks) | 
| Percentage of Subjects Achieving an MCID (Minimal Clinically Important Difference) of 4 Units or More in SGRQ at Week 24 | The SGRQ (St. George's Respiratory Questionnaire) is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of BFF MDI, FF MDI, BD MDI, & Symbicort TBH on health-related quality of life as compared to placebo in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life. | at Week 24 | 
| Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 (BFF MDI vs BD MDI) | Change from baseline in morning pre-dose trough FEV1(Forced Expiratory Volume in 1 second) at Week 24 (BFF MDI vs BD MDI) | at Week 24 | 
| Peak Change From Baseline in FEV1 at Week 24 (BFF MDI vs BD MDI) | Peak change from baseline in FEV1 (Forced Expiratory Volume in 1 second) at Week 24 (BFF MDI vs BD MDI) | at Week 24 | 
| Change From Baseline in Average Daily Rescue Ventolin HFA Use Over 24 Weeks (BFF MDI vs BD MDI) | Change from baseline in average daily rescue Ventolin HFA use over 24 weeks (BFF MDI vs BD MDI) | over 24 Weeks | 
| FEV1 on Day 1, 5 Minutes, Time to Onset of Action Determination | Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. | Day 1 - 5 Minutes | 
| FEV1 on Day 1, 15 Minutes, Time to Onset of Action Determination | Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. | Day 1 - 15 Minutes | 
| FEV1 on Day 1, 30 Minutes, Time to Onset of Action Determination | Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. | Day 1 - 30 Minutes | 
| FEV1 on Day 1, 1 Hour, Time to Onset of Action Determination | Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. | Day 1 - 1 Hour | 
| FEV1 on Day 1, 2 Hours, Time to Onset of Action Determination | Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. | Day 1 - 2 Hours | 
| FEV1 on Day 1, 4 Hours, Time to Onset of Action Determination | Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. | Day 1 - 4 Hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD