Efficacy and Safety of Four Doses of Glycopyrronium Bromide (NVA237) in Patients With Stable Chronic Obstructive Pulmonary Disease (COPD), in Comparison to an Active Comparator Tiotropium

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of glycopyrronium bromide (NVA237) in patients with stable COPD, in comparison to an active comparator.

Official Title
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A Randomized, Double-blind, Placebo-controlled, 4 Period Incomplete Block Cross-over, Multi-center, Multiple Dose (7 Days) Dose-ranging Study to Assess the Efficacy and Safety of 4 Doses of NVA237 in Patients With Stable COPD, Compared to Seven Days Treatment With Tiotropium (18μg Once Daily, Open Label) as an Active Control

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: NVA237
* Drug: Placebo
* Drug: Tiotropium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adults aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure. Patients with moderate to severe COPD according to the Gold Guidelines (2006). Patients who have smoking history of at least 10 pack years. Ten pack-years is defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc. Patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥30% and < 80% of the predicted normal, and post-bronchodilator FEV1/forced vital capacity (FVC) < 0.7 at Visit 2. For non-Japanese patients predicted FEV1 should be calculated according to Quanjer predictive equations [Quanjer PH 1993], for Japanese patients predicted FEV1 should be calculated according to Japanese Respiratory Society predictive tables [Japan Respiratory Society 2001]. Exclusion Criteria: Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test). Patients requiring oxygen therapy on a daily basis for chronic hypoxemia, or who have been hospitalized for an exacerbation of their airways disease in the 6 weeks prior to Visit 1 or between Visit 1 and Visit 3. Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1. Patients who develop a respiratory tract infection during the screening period (up to Visit 3) must discontinue from the trial, but will be permitted to re-enroll at a later date (at least 6 weeks after the resolution of the respiratory tract infection). Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to) unstable ischemic heart disease, cancers, left ventricular failure, long term prednisone therapy, history of myocardial infarction, arrhythmia (all), narrow angle glaucoma, symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment. Patients with a history of asthma indicated by (but not limited to): Blood eosinophil count > 400/mm3 Onset of symptoms prior to age 40 years. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 40 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: NVA237 12.5 µg<br>12.5 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence. | Drug: NVA237<br>* single-dose dry-powder inhaler (SDDPI)<br>|
| Experimental: NVA237 25 µg<br>25 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence. | Drug: NVA237<br>* single-dose dry-powder inhaler (SDDPI)<br>|
| Experimental: NVA237 50 µg<br>50 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence. | Drug: NVA237<br>* single-dose dry-powder inhaler (SDDPI)<br>|
| Experimental: NVA237 100 µg<br>100 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence. | Drug: NVA237<br>* single-dose dry-powder inhaler (SDDPI)<br>|
| Placebo Comparator: Placebo<br>Placebo via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence. | Drug: Placebo<br>* single-dose dry-powder inhaler (SDDPI)<br>|
| Active Comparator: Tiotropium 18 µg<br>18 µg od via Handihaler inhaler. Tiotropium was given open-label. At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence. | Drug: Tiotropium<br>* Handihaler inhaler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in 1 Second (FEV1) Following 7 Days of Treatment | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The trough in FEV1 was defined as the mean of two measurements at 23h 15min and 23h 45min post dosing. | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Least Squares Means of FEV1 (L) at Day 1, by Timepoint | FEV1 was measured at 5, 15, 30 minutes, 1, 2, 3, 4, 5, 23 hours and 15 minutes, and 23 hours and 45 minutes post dose. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Age≥40 yrs, Glycopyrronium Bromide