Study to Evaluate the Safety and Efficacy of Inhaled PT005 in Patients With Chronic Obstructive Pulmonary Disease (COPD)

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 PT005 compared to placebo and Formoterol Fumarate (Foradil Aerolizer) in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Official Title
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A Randomized, Double-blind, Five-period, Placebo and Active-controlled,Cross-over, Multi-centre, Study Evaluating Single Administration of Three Doses of Inhaled PT005 in Patients With Moderate-to-Severe COPD, Compared to Open- Label Marketed Formoterol (FORADIL® AEROLIZER®) as an Active Control

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Inhaled PT005
* Drug: Inhaled PT005
* Drug: Inhaled PT005
* Drug: Inhaled placebo
* Drug: Formoterol Fumarate 12 mcg (Foradil Aerolizer)


Participation Criteria
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Eligibility Criteria
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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-salbutamol FEV1/FVC ratio of < or = 0.70 A measured post-salbutamol FEV1 > or = 40 and < or = 80% of predicted normal values Demonstrated reversibility to a short acting beta agonist by either >12% and >150 ml improvement in baseline FEV1, 30 minutes following administration of 4 puffs of salbutamol MDI or an absolute improvement of >200 ml in baseline FEV1, 30 minutes following administration of 4 puffs of salbutamol MDI. Competent at using the inhalation device 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 24 weeks of Screening Poorly controlled COPD in prior 6-weeks, defined as the occurrence of acute worsening of COPD requiring corticosteroids or antibiotics or acute worsening of COPD requiring treatment prescribed by a physician Clinically significant medical conditions Lower respiratory tract infection requiring antibiotics in past 6 weeks Clinically significant abnormal ECG Clinically significant 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 the medications below in specified time interval prior to Screening: 12-weeks: depot corticosteroids, intra-articular corticosteroids; 4 weeks: ICS >1000 μg/day of fluticasone propionate or equivalent, non-potassium sparing diuretics, P-glycoprotein inhibitors, CYP3A4 inhibitors; 1 week: tiotropium; 48 hours: oral beta agonists, long acting beta agonists, theophylline, zariflukast, montelukast, zileuton; 8 hours: ipratropium or ipratropium/salbutamol combination product, inhaled short acting beta agonists, xanthine containing foods Use of the following medications is prohibited: tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, beta-adrenergic antagonists, anticonvulsants (barbiturates,hydantoins, and carbamazepine and phenothiazines Receiving long-term-oxygen or nocturnal oxygen therapy for >12 hours a day Diagnosis of sleep apnea that is uncontrolled Participation in acute phase of pulmonary rehabilitation in prior 4 weeks or will enter acute phase of pulmonary rehabilitation program during study Unable to comply with study procedures Affiliated with Investigator site Questionable validity of consent A positive drug of abuse test at Screening lives prior to Screening, whichever is longer

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Inhaled PT005 2.4 mcg | Drug: Inhaled PT005<br>* single dose, inhaled<br>|
| Experimental: 2<br>Inhaled PT005 4.8 mcg | Drug: Inhaled PT005<br>* single dose, inhaled<br>|
| Experimental: 3<br>Inhaled PT005 9.6 mcg | Drug: Inhaled PT005<br>* single dose, inhaled<br>|
| Placebo Comparator: 4<br>Inhaled Placebo | Drug: Inhaled placebo<br>* single dose, inhaled<br>|
| Active Comparator: 5<br>Formoterol Fumarate 12 mcg (Foradil Aerolizer) | Drug: Formoterol Fumarate 12 mcg (Foradil Aerolizer)<br>* single dose, Formoterol Fumarate 12 mcg administered via the Aerolizer<br>* Other names: Foradil Aerolizer;|

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 three doses of inhaled PT005 compared with placebo. |  | Serial FEV1 measured over 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of action (>10% improvement in FEV1 from baseline) |  | Serial FEV1 measured over 12 hours | 
| Peak FEV1 |  | Serial FEV1 measured over 12 hours | 
| Trough FEV1 |  | Serial FEV1 measured over 12 hours | 
| Peak inspiratory capacity (IC) |  | Serial IC measured over 12 hours | 
| Peak expiratory flow rate (PEFR) |  | Serial PEFR measured over 12 hours | 
| Forced vital capacity (FVC) |  | Serial FVC measured over 12 hours | 

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