Evaluation of Efficacy on Exercise Tolerance of Symbicort (Budesonide/Formoterol) Compared to Placebo and Oxis in Patients With Severe COPD

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect on exercise tolerance, lung function and symptoms after treatment with Symbicort, Oxis or placebo in patients with severe chronic obstructive pulmonary disease.

Official Title
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A Multi-centre, Randomised, Double-blind, Cross-over Design Study to Evaluate Efficacy on Exercise Tolerance of Symbicort ®(Budesonide/Formoterol) 320/9μg One Inhalation Twice Daily Compared With Placebo and Oxis® 9μg One Inhalation Twice Daily in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD).

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: budesonide/formoterol Turbuhaler 320/9µg
* Drug: formoterol Turbuhaler 9µg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >=40 years of age diagnosed COPD with symptoms >= 2 years pre-bronchodilatory FEV1 <=50% of PN Exclusion Criteria: Current respiratory tract disorder other than COPD history of asthma or rhinitis significant or unstable cardiovascular disorder

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: Symbicort then Formoterol then Placebo<br>Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily, then Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily, then Placebo, 1 inhalation twice daily | Drug: budesonide/formoterol Turbuhaler 320/9µg<br>* Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms<br>Drug: formoterol Turbuhaler 9µg<br>* Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily<br>Other: Placebo<br>* Placebo, 1 inhalation twice daily<br>|
| Experimental: Formoterol then Symbicort then Placebo<br>Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily, then Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily, then Placebo, 1 inhalation twice daily | Drug: budesonide/formoterol Turbuhaler 320/9µg<br>* Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms<br>Drug: formoterol Turbuhaler 9µg<br>* Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily<br>Other: Placebo<br>* Placebo, 1 inhalation twice daily<br>|
| Placebo Comparator: Placebo then Formoterol then Symbicort<br>Placebo, 1 inhalation twice daily, then Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily, then Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily | Drug: budesonide/formoterol Turbuhaler 320/9µg<br>* Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms<br>Drug: formoterol Turbuhaler 9µg<br>* Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily<br>Other: Placebo<br>* Placebo, 1 inhalation twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise Endurance Time (EET) at 75% of Peak Work Capacity With Cycle Ergometry 1 Hour Post-dose | Treatment means from individual patient data. Patients with only one EET value where excluded since this model, with patient and period as fixed factors, required data from at least two periods. | Single measurement taken1 hour post-dose at the end of each 1-week treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise Endurance Time (EET) at 75% of Peak Work Capacity With Cycle Ergometry 6 Hour Post-dose | Treatment means from individual patient data. Patients with only one EET value where excluded since this model, with patient and period as fixed factors, required data from at least two periods. | Single measurement taken 6 hours post-dose at the end of each 1-week treatment period | 
| Forced Expiratory Flow (FEV1) Pre-dose | The mean of the changes for each patient between the pre-dose value at the start of treatment and the pre-dose value after one week of treatment. | Pre-dose at the start of treatment and pre-dose after one week of treatment | 
| Forced Vital Capacity (FVC) Pre-dose | The mean of the changes for each patient between the pre-dose value at the start of treatment and the pre-dose value after one week of treatment. | Pre-dose at the start of treatment and pre-dose after one week of treatment | 
| Vital Capacity (VC) Pre-dose (Change From Pre-treatment to Treatment) | The mean of the changes for each patient between the pre-dose value at the start of treatment and the pre-dose value after one week of treatment. | Pre-dose at the start of treatment and pre-dose after one week of treatment | 
| Peak Expiratory Flow (PEF) Before Morning Dose | The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period. | Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period | 
| Sleep Score | The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (symptoms did not cause a sleep problem) to 4 (did not sleep at all due to symptoms). | Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period | 
| Breathlessness Score | The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (unaware of any difficulty in breathing) to 4 (almost constant difficulties in breathing). All patients with data from both periods are included. | Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period | 
| Chest Tightness Score | The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (unaware of any discomfort) to 4 (almost constant discomfort). | Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period | 
| Cough Score | The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (unaware of coughing) to 4 (never free of need to cough). | Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period | 
| Number of Inhalations of Reliever Medication | The change in average daily use for the run-in or wash-out period to the average daily use of the subsequent treatment period. | Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period | 
| Borg CR10 Score Before Exercise Endurance Time (EET) Performed 1 Hour Post-dose | The Borg CR10 Scale consists of 10-point score that the patients pointed to so as to indicate their level of dyspnea before and during exercise testing (where 0 indicates no breathlessness at all and 10 indicates maximum breathlessness. Patients are allowed to assign an even higher number depending on their perceived level of breathlessness). | Single measurement performed at rest prior to exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period | 
| Borg CR10 Score After Exercise Endurance Time (EET) Performed 1 Hour Post-dose | The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort). | Single measurement performed after exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period | 
| Borg CR10 Score Before Exercise Endurance Time (EET) Performed 6 Hour Post-dose | The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort). | Single measurement performed at rest prior to exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period | 
| Borg CR10 Score After Exercise Endurance Time (EET) Performed 6 Hours Post-dose | The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort). All patients with data are included. | Single measurement performed after exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period | 
| Inspiratory Capacity (IC) Before Exercise Endurance Time (EET) Performed 1 Hour Postdose | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period | 
| Inspiratory Capacity (IC) Before Exercise Endurance Time (EET) Performed 6 Hours Post-dose | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period | 
| Vital Capacity (VC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET) | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period | 
| Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET) | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 1hour post-dose at the end of each 1-week treatment period | 
| Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET) | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period | 
| Residual Volume (RV) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET) | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period | 
| Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET) | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period | 
| Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET) | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period | 
| Vital Capacity (VC) (Body Plethysmography) Performed Before 6 Hour Exercise Endurance Time (EET) | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period | 
| Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET) | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period | 
| Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET) | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period | 
| Residual Volume (RV) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET) | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 6 hous post-dose at the end of each 1-week treatment period | 
| Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET) | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period | 
| Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 6 Hours Post-dose EET | Treatment means from individual participant data. | Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period | 
| SGRQ-C (St. George's Respiratory Questionnaire for COPD Patients) Total Score | Score from a questionnaire, with scores ranging form 0 (perfect health) to 100 (worst possible state). Includes all patients with data. | Single measurement taken at the end of each 1-week treatment period | 

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