Efficacy and Tolerability of Symbicort as an add-on Treatment to Spiriva Compare With Spiriva Alone in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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This is a multicentre study with a randomised, parallel group, open-label, 3-month phase IV design to assess the efficacy and tolerability of Symbicort as an add-on treatment to Spiriva compare with Spiriva alone in patients with severe chronic obstructive pulmonary disease (COPD).

Official Title
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A Randomised, Parallel-group, Open-label, Multicentre, 3-month Phase IV, Efficacy and Tolerability Study of Budesonide/Formoterol (Symbicort® Turbuhaler® 160/4.5μg/Inhalation, 2 Inhalations Twice Daily) Added to Tiotropium (SpirivaTM 18 μg/Inhalation, 1 Inhalation Once Daily) Compared With Tiotropium (SpirivaTM18 μg/Inhalation, 1 Inhalation Once Daily) Alone in Severe Chronic Obstructive Pulmonary Disease (COPD) Patients

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: Budesonide/formoterol (Symbicort® Turbuhaler®)
* Drug: Tiotropium (SpirivaTM)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent Men or women patients ≥40 years of age Diagnosis of COPD with symptoms for more than 2 years and there is a history of at least one COPD exacerbation requiring a course of oral steroids and/or antibiotics within 1-12 months before Visit 2 Forced Expiratory Volume in 1 second (FEV1) ≤50% of predicted normal value, pre-bronchodilator and Forced Expiratory Volume in 1 second (FEV1) / Forced Vital Capacity (FVC) < 70%, pre-bronchodilator Total symptom score of 2 or more per day for at least half of run-in period (breathing, cough and sputum scores from the diary card) and complete morning recordings of Digital Peak Flow Meter data at least 7 out of the last 10 days of the run-in period Exclusion Criteria: A history of asthma and seasonal allergic rhinitis before 40 years of age Patients who have experienced exacerbation of COPD requiring hospitalisation and /or emergency room treatment and/or a course of oral steroids and/or intravenous corticosteroids and/or antibiotics within 4 weeks prior to Visit 2 and/or during run-in period and also the patients who use of systemic glucocorticosteroids (GCS) within 4 weeks and/or inhaled GCS within 2 weeks prior to Visit 2 and/or during run-in period Patients with relevant cardiovascular disorder judged by the investigator Patients with glaucoma, prostatic hyperplasia or bladder-neck obstruction judged by the investigator Women who are pregnant, breast-feeding or of child-bearing potential judged by the investigator

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>Add-on treatment | Drug: Budesonide/formoterol (Symbicort® Turbuhaler®)<br>* Budesonide/formoterol (Symbicort® Turbuhaler®) 160/4.5μg/inhalation, 2 inhalations twice daily<br>Drug: Tiotropium (SpirivaTM)<br>* Tiotropium (SpirivaTM) 18 μg/inhalation, 1 inhalation once daily<br>|
| Other: 2<br>Add-on treatment | Drug: Tiotropium (SpirivaTM)<br>* Tiotropium (SpirivaTM) 18 μg/inhalation, 1 inhalation once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre-dose FEV1 | Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value | Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-dose FEV1 at 5 Minutes | Ratio of post-dose FEV1 at 5 minutes to baseline value | Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drug | 
| Post-dose FEV1 at 60 Minutes | Ratio of post-dose FEV1 at 60 minutes to baseline value | Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12) | 
| Pre-dose FVC | Ratio of pre-dose FVC (Forced Vital Capacity) in treatment period to baseline value | Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12) | 
| Post-dose FVC at 5 Minutes | Ratio of post-dose FVC at 5 minutes to baseline value | Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 5 minutes after inhalation of study drug at weeks 0, 1, 6, 12) | 
| Post-dose FVC at 60 Minutes | Ratio of post-dose FVC at 60 minutes to baseline value | Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12) | 
| Pre-dose IC | Ratio of pre-dose IC (Inspiratory Capacity) in treatment period to baseline value | Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug | 
| Post-dose IC at 60 Minutes | Ratio of post-dose IC at 60 minutes to baseline value | Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12) | 
| Pre-dose PEF in Last Week of Treatment | Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to last week of treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the last week of treatment, up to 12 weeks | 
| Pre-dose PEF in First Week of Treatment | Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to first week of treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the first week of treatment | 
| Pre-dose PEF in Whole Treatment Period | Change in pre-dose morning PEF from run-in period to whole treatment period | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in whole treatment period of 12 weeks | 
| Post-dose PEF in Last Week of Treatment | Change in post-dose morning PEF at 5 minutes from run-period to last week of treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the last week of treatment, up to 12 weeks | 
| Post-dose PEF in First Week of Treatment | Change in post-dose morning PEF at 5 minutes from run-in period to first week of treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the first week of treatment | 
| Post-dose PEF in Whole Treatment Period | Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in whole treatment period of 12 weeks | 
| Use of Reliever Medication During Day in the Last Week on Treatment | Change in the number of inhalations of reliever medication during day from run-in period to the last week on treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment, up to 12 weeks | 
| Use of Reliever Medication During Day in the First Week on Treatment | Change in the number of inhalations of reliever medication during day from run-in period to the first week on treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the first week on treatment | 
| Use of Reliever Medication During Day in the Whole Treatment Period | Change in the number of inhalations of reliever medication during day from run-in period to the whole treatment period | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period of 12 weeks | 
| Use of Reliever Medication During Night in the Last Week on Treatment | Change in the number of inhalations of reliever medication during night from run-in period to the last week on treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment, up to 12 weeks | 
| Use of Reliever Medication During Night in the First Week on Treatment | Change in the number of inhalations of reliever medication during day from run-in period to the first week on treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the first week on treatment | 
| Use of Reliever Medication During Night in the Whole Treatment Period | Change in the number of inhalations of reliever medication during night from run-in period to the whole treatment period | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period of 12 weeks | 
| Change in COPD Symptoms - Breathing | Change in breathing symptom score (from 0:none to 4:severe) from run-in period | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks | 
| Change in COPD Symptoms - Cough | Change in Cough symptom score (from 0:none to 4:severe) from run-in period | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks | 
| Change in COPD Symptoms - Sputum | Change in Sputum symptom score (from 0:none to 4:severe) from run-in period | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks | 
| COPD Exacerbations | Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms | Whole treatment period of 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe chronic obstructive pulmonary disease (COPD) patients