Study to Evaluate the Safety and Efficacy of Inhaled PT001 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 PT001 compared to placebo and tiotropium in patients with mild to moderate chronic obstructive pulmonary disease (COPD).

Official Title
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A Randomized, Double-blind, Single Dose, Four-period, Six-treatment, Placebo-controlled, Balanced, Incomplete Block, Cross-over, Study of Four Doses of Inhaled PT001 in Patients With Mild to Moderate COPD, Compared to Open Label Tiotropium

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Inhaled PT001
* Drug: Inhaled Placebo
* Drug: Tiotropium Handihaler


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent 40 - 75 years of age Females of non-child bearing potential or females of child bearing potential with negative pregnancy test; and acceptable contraceptive methods COPD diagnosis Current/former smokers with at least a 10 pack-year history of cigarette smoking Patients with established clinical history of COPD and severity defined as a post-ipratropium FEV1/FVC ratio of ≤0.70 and FEV1 ≥50 and ≤85% of predicted normal at Screening Must demonstrate reversibility to ipratropium demonstrated by a >200 mL improvement over baseline and/or >12% and >150 mL improvement over baseline Patients willing to stay at study site for at least 24 hours on each test day 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 Unable to perform acceptable spirometry 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 Symptomatic prostatic hypertrophy or bladder neck obstruction Known narrow-angle glaucoma 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 anticholinergics History of severe milk protein allergy Known or suspected history of alcohol or drug abuse Medically unable to withhold short acting bronchodilators for 6-hours Use of the medications below in specified time interval prior to Screening: 3 months: depot corticosteroids, intra-articular corticosteroids; 6 weeks: oral corticosteroids, antibiotics administered for a COPD exacerbation; and 1 month: P-glycoprotein inhibitors, CYP450 3A4 inhibitors, ICS >1000 μg/day of fluticasone propionate or equivalent The following COPD medications need to be stopped and switched to appropriate replacement therapies: tiotropium, oral beta2 agonists, LABAs, combination corticosteroid/LABAs, theophylline, leukotriene inhibitors,cromoglycate and nedocromil 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 Will enter acute phase of pulmonary rehabilitation program during study Unable to comply with study procedures Affiliated with Investigator site Questionable validity of consent Use of investigational study drug/participation in clinical study in the last 30 days or 5 half lives prior to Screening, whichever is longer

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: PT001 18 mcg<br>Inhaled PT001 18 mcg | Drug: Inhaled PT001<br>* single dose, inhaled<br>|
| Experimental: PT001 36 mcg<br>Inhaled PT001 36 mcg | Drug: Inhaled PT001<br>* single dose, inhaled<br>|
| Experimental: PT001 72 mcg<br>Inhaled PT001 72 mcg | Drug: Inhaled PT001<br>* single dose, inhaled<br>|
| Experimental: PT001 144 mcg<br>Inhaled PT001 144 mcg | Drug: Inhaled PT001<br>* single dose, inhaled<br>|
| Placebo Comparator: Inhaled Placebo<br>Inhaled Placebo | Drug: Inhaled Placebo<br>* single dose, inhaled<br>|
| Active Comparator: Tiotropium Handihaler<br>Tiotropium 18 mcg administered via Handihaler | Drug: Tiotropium Handihaler<br>* single dose, tiotropium 18 mcg administered via the Handihaler<br>* Other names: Spiriva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak improvement in forced expiratory volume in one second (FEV1) | Day 1 serial FEV1 measured over 24 hours | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of action (>10% improvement in FEV1 from baseline) | Day 1 serial FEV1 measured over 24 hours | Day 1 | 
| Time to peak FEV1 | Day 1 serial FEV1 measured over 24 hours | Day 1 | 
| FEV1 area under the curve (AUC) from 0 to 24 hours | Day 1 serial FEV1 measured over 24 hours | Day 1 | 
| FEV1 AUC from 0 to 12 hours | Day 1 serial FEV1 measured over 24 hours | Day 1 | 
| Trough FEV1 at 12 and 24 hours | Day 1 serial FEV1 measured over 24 hours | Day 1 | 
| Peak Improvement in inspiratory capacity (IC) | Day 1 serial IC measured over 24 hours | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, obstructive lung diseases, Tiotropium