Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD (PINNACLE 2)

Study Overview
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Brief Summary
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This is a multicenter, randomized, double-blind, parallel group, chronic-dosing (24 weeks), placebo-controlled study to assess the efficacy and safety of Glycopyrrolate (GP and Formoterol Fumarate (FF) combination metered-dose inhaler (MDI) (GFF; PT003), GP MDI (PT001), and FF MDI (PT005) compared with Placebo MDI in subjects with moderate to very severe COPD.

Official Title
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A Randomized, Double-Blind (Test Products and Placebo), Chronic Dosing (24 Weeks), Placebo-Controlled, Parallel Group, Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD, Compared With Placebo

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: GFF MDI (PT003)
* Drug: GP MDI (PT001)
* Drug: FF MDI (PT005)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female subjects at least 40 years of age and no older than 80 at Visit 1. 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. Subjects with FEV1/FVC ratio of <0.70 and FEV1 <80% predicted normal and ≥750 mL if FEV1 <30% of predicted normal value. Subjects willing and, in the opinion of the investigator, able to adjust current COPD therapy as required by the protocol Key Exclusion Criteria: Significant diseases other than COPD, i.e. disease or condition which, in the opinion of the investigator, may put the patient 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 Current diagnosis of asthma or alpha-1 antitrypsin deficiency Other active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or uncontrolled sleep apnea Hospitalized due to poorly controlled COPD within 3 months prior to screening or during the Screening Period Poorly controlled COPD, defined as acute worsening of COPD that requires treatment with oral corticosteroids or antibiotics within 6 weeks prior to screening or during the Screening Period Lower respiratory tract infections that required antibiotics within 6 weeks prior to screening or during the Screening Period Unstable ischemic heart disease, left ventricular failure, or documented myocardial infarction within 12 months of enrollment. Recent history of acute coronary syndrome, percutaneous coronary intervention, coronary artery bypass graft within the past three months Congestive heart failure (CHF NYHA Class III/IV) Clinically significant abnormal 12-lead ECG Abnormal liver function tests defined as AST, ALT, or total bilirubin ≥ 1.5 times upper limit of normal at Visit 1 and on repeat testing Cancer not in complete remission for at least five years History of hypersensitivity to β2-agonists, glycopyrronium or other muscarinic anticholinergics, lactose/milk protein or any component of the MDI Other protocol-defined inclusion/exclusion criteria may apply

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FF MDI (PT005)<br>FF MDI administered as two puffs BID | Drug: FF MDI (PT005)<br>* FF MDI administered as two puffs BID<br>* Other names: formoterol fumarate metered dose inhaler (FF MDI);|
| Experimental: GP MDI (PT001)<br>GP MDI administered as two puffs BID | Drug: GP MDI (PT001)<br>* GP MDI administered as two puffs BID<br>* Other names: glycopyrrolate metered dose inhaler (GP MDI);|
| Experimental: GFF MDI (PT003)<br>GFF MDI administered as two puffs BID | Drug: GFF MDI (PT003)<br>* GFF MDI administered as two puffs BID<br>* Other names: (GFF MDI);|
| Placebo Comparator: Placebo MDI<br>Inhaled placebo administered as two puffs BID | Drug: Placebo<br> <br> |

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 | Change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV1) at Week 24. | At Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks | Change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV1) over 24 weeks. FEV1 was assessed at multiple time points post-baseline, and a model-based average of all visits starting from Week 2 through week 24 inclusive was calculated. The change values reported in the table represent the change between the baseline and the average FEV1 post-baseline. | Over 24 weeks | 
| Peak FEV1 | Peak change from baseline in FEV1 within 2 hours post-dosing at Week 24 | At week 24 | 
| St. George Respiratory Questionnaire (SGRQ) Score | Change from baseline in the SGRQ total score at Week 24. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI 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. | 24 weeks | 
| Rescue Ventolin HFA Use | Change from baseline in average daily rescue Ventolin HFA use over 24 weeks | 24 weeks | 
| Onset of Action as Assessed by FEV1 | Defined as the first time-point using the 5- and 15-minute post dose measurements where the difference in FEV1 from Placebo was statistically significant | Day 1 |