Efficacy and Safety of Two Doses of Formoterol Fumarate MDI (PT005) in Patients With Stable Chronic Obstructive Pulmonary Disease (COPD), Compared to Foradil® Aerolizer® as an Active Control

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of inhaled formoterol fumarate (7.2 and 9.6 µg ex-actuator) compared to placebo and Foradil Aerolizer in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).

Official Title
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A Phase IIb, Multi-center, Randomized, Double-blind, Placebo-controlled, Multi-dose, Four-period, Cross-over Study of Two Doses of Formoterol Fumarate MDI (PT005; 7.2 and 9.6 µg Ex-actuator), Administered Twice Daily for 1 Week in Patients With Moderate to Very Severe COPD, Compared to Open Label Marketed Formoterol Fumarate Inhalation Powder (Foradil® Aerolizer®, 12 µg) as an Active Control

Conditions
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COPD

Intervention / Treatment
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* Drug: Inhaled PT005
* Drug: Inhaled Placebo
* Drug: Formoterol Fumarate 12 µg (Foradil Aerolizer)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Signed written informed consent 40 - 80 years of age Fluency in written and spoken English Females of non-child bearing potential or females of child bearing potential with negative pregnancy test; and acceptable contraceptive methods Current/former smokers with at least a 10 pack-year history of cigarette smoking A measured post- bronchodilator FEV1/FVC ratio of < or = 0.70 A measured post- bronchodilator FEV1 > or = 750ml or 30% predicted and < or = 80% of predicted normal values Competent at using the inhalation device Key Exclusion Criteria: Women who are pregnant or lactating Primary diagnosis of asthma Alpha-1 antitrypsin deficiency as the cause of COPD Active pulmonary diseases Prior lung volume reduction surgery Abnormal chest X-ray (or CT scan) not due to the presence of COPD Hospitalized due to poorly controlled COPD within 12 weeks of Screening Poorly controlled COPD, defined as the occurrence of acute worsening of COPD requiring corticosteroids or antibiotics or acute worsening of COPD requiring treatment prescribed by a physician within 6 weeks of screening or between screening and visit 2 Lower respiratory tract infection requiring antibiotics within 6 weeks of screening Clinically significant medical conditions that preclude participation in the study (e.g. clinically significant abnormal ECG or uncontrolled hypertension) Positive Hepatitis B surface antigen or Hepatitis C antibody Cancer that has not been in complete remission for at least 5 years History of hypersensitivity to any beta2-agonists or any study drug component History of severe milk protein allergy Known or suspected history of alcohol or drug abuse Medically unable to withhold short acting bronchodilators for 8-hours Use of prohibited medications prior to screening and during the study as specified in the protocol Receiving long-term-oxygen or nocturnal oxygen therapy for >12 hours a day Participation in acute phase of pulmonary rehabilitation within 4 weeks of screening or will enter acute phase of pulmonary rehabilitation program during study Unable to comply with study procedures Prior participation in a Pearl PT005 study Requires use of a spacer due to poor hand-to-breath coordination

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled PT005 7.2 µg<br> | Drug: Inhaled PT005<br>* inhaled, twice daily for 1 week duration<br>|
| Experimental: Inhaled PT005 9.6 µg<br> | Drug: Inhaled PT005<br>* inhaled, twice daily for 1 week duration<br>|
| Placebo Comparator: Inhaled Placebo<br> | Drug: Inhaled Placebo<br>* inhaled, twice daily for 1 week duration<br>|
| Active Comparator: Formoterol Fumarate 12 µg (Foradil Aerolizer)<br> | Drug: Formoterol Fumarate 12 µg (Foradil Aerolizer)<br>* inhaled, twice daily for 1 week duration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in forced expiratory volume in one second (FEV1) area under the curve from 0 to 12 hours [AUC(0-12)] from test day baseline across the two doses of inhaled PT005 compared with placebo. |  | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung Function Measures on Day 7 as measured by spirometry. |  | Day 7 | 
| Safety measures including electrocardiograms (ECGs), vital signs, physical exam, clinical laboratory testing, and adverse events of special interest |  | Day 7 |