Back to resultsEvaluation of Efficacy on Exercise Tolerance of Symbicort (Budesonide/Formoterol) Compared to Placebo and Oxis in Patients With Severe COPD (CODEX)
Primary Purpose
Chronic Obstructive Pulmonary Disease
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
budesonide/formoterol Turbuhaler 320/9µg
formoterol Turbuhaler 9µg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring COPD
Eligibility Criteria
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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Symbicort then Formoterol then Placebo
Formoterol then Symbicort then Placebo
Placebo then Formoterol then Symbicort
Arm Description
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
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
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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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).
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.
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).
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).
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.
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).
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).
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).
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.
Inspiratory Capacity (IC) Before Exercise Endurance Time (EET) Performed 1 Hour Postdose
Treatment means from individual participant data.
Inspiratory Capacity (IC) Before Exercise Endurance Time (EET) Performed 6 Hours Post-dose
Treatment means from individual participant data.
Vital Capacity (VC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET)
Treatment means from individual participant data.
Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)
Treatment means from individual participant data.
Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)
Treatment means from individual participant data.
Residual Volume (RV) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)
Treatment means from individual participant data.
Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET)
Treatment means from individual participant data.
Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)
Treatment means from individual participant data.
Vital Capacity (VC) (Body Plethysmography) Performed Before 6 Hour Exercise Endurance Time (EET)
Treatment means from individual participant data.
Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET)
Treatment means from individual participant data.
Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET)
Treatment means from individual participant data.
Residual Volume (RV) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET)
Treatment means from individual participant data.
Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET)
Treatment means from individual participant data.
Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 6 Hours Post-dose EET
Treatment means from individual participant data.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00489853
Brief Title
Evaluation of Efficacy on Exercise Tolerance of Symbicort (Budesonide/Formoterol) Compared to Placebo and Oxis in Patients With Severe COPD
Acronym
CODEX
Official Title
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).
Study Type
Interventional
2. Study Status
Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
August 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
COPD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
137 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Symbicort then Formoterol then Placebo
Arm Type
Experimental
Arm Description
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
Arm Title
Formoterol then Symbicort then Placebo
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo then Formoterol then Symbicort
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
budesonide/formoterol Turbuhaler 320/9µg
Intervention Description
Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms
Intervention Type
Drug
Intervention Name(s)
formoterol Turbuhaler 9µg
Intervention Description
Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo, 1 inhalation twice daily
Primary Outcome Measure Information:
Title
Exercise Endurance Time (EET) at 75% of Peak Work Capacity With Cycle Ergometry 1 Hour Post-dose
Description
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.
Time Frame
Single measurement taken1 hour post-dose at the end of each 1-week treatment period
Secondary Outcome Measure Information:
Title
Exercise Endurance Time (EET) at 75% of Peak Work Capacity With Cycle Ergometry 6 Hour Post-dose
Description
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.
Time Frame
Single measurement taken 6 hours post-dose at the end of each 1-week treatment period
Title
Forced Expiratory Flow (FEV1) Pre-dose
Description
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.
Time Frame
Pre-dose at the start of treatment and pre-dose after one week of treatment
Title
Forced Vital Capacity (FVC) Pre-dose
Description
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.
Time Frame
Pre-dose at the start of treatment and pre-dose after one week of treatment
Title
Vital Capacity (VC) Pre-dose (Change From Pre-treatment to Treatment)
Description
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.
Time Frame
Pre-dose at the start of treatment and pre-dose after one week of treatment
Title
Peak Expiratory Flow (PEF) Before Morning Dose
Description
The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period.
Time Frame
Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period
Title
Sleep Score
Description
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).
Time Frame
Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period
Title
Breathlessness Score
Description
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.
Time Frame
Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period
Title
Chest Tightness Score
Description
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).
Time Frame
Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period
Title
Cough Score
Description
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).
Time Frame
Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period
Title
Number of Inhalations of Reliever Medication
Description
The change in average daily use for the run-in or wash-out period to the average daily use of the subsequent treatment period.
Time Frame
Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period
Title
Borg CR10 Score Before Exercise Endurance Time (EET) Performed 1 Hour Post-dose
Description
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).
Time Frame
Single measurement performed at rest prior to exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
Title
Borg CR10 Score After Exercise Endurance Time (EET) Performed 1 Hour Post-dose
Description
The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort).
Time Frame
Single measurement performed after exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
Title
Borg CR10 Score Before Exercise Endurance Time (EET) Performed 6 Hour Post-dose
Description
The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort).
Time Frame
Single measurement performed at rest prior to exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
Title
Borg CR10 Score After Exercise Endurance Time (EET) Performed 6 Hours Post-dose
Description
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.
Time Frame
Single measurement performed after exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
Title
Inspiratory Capacity (IC) Before Exercise Endurance Time (EET) Performed 1 Hour Postdose
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
Title
Inspiratory Capacity (IC) Before Exercise Endurance Time (EET) Performed 6 Hours Post-dose
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
Title
Vital Capacity (VC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET)
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
Title
Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 1hour post-dose at the end of each 1-week treatment period
Title
Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
Title
Residual Volume (RV) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
Title
Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET)
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
Title
Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
Title
Vital Capacity (VC) (Body Plethysmography) Performed Before 6 Hour Exercise Endurance Time (EET)
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
Title
Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET)
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
Title
Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET)
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
Title
Residual Volume (RV) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET)
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 6 hous post-dose at the end of each 1-week treatment period
Title
Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET)
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
Title
Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 6 Hours Post-dose EET
Description
Treatment means from individual participant data.
Time Frame
Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
Title
SGRQ-C (St. George's Respiratory Questionnaire for COPD Patients) Total Score
Description
Score from a questionnaire, with scores ranging form 0 (perfect health) to 100 (worst possible state). Includes all patients with data.
Time Frame
Single measurement taken at the end of each 1-week treatment period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tomas Andersson, MD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Heinrich Worth, MD
Organizational Affiliation
Akademisches Lehrkrankenhaus der Universität Erlangen-Nürnberg, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Berlin
Country
Germany
Facility Name
Research Site
City
Erfurt
Country
Germany
Facility Name
Research Site
City
Fulda
Country
Germany
Facility Name
Research Site
City
Furth
Country
Germany
Facility Name
Research Site
City
Geesthacht
Country
Germany
Facility Name
Research Site
City
Grobhansdorf
Country
Germany
Facility Name
Research Site
City
Leipzig
Country
Germany
Facility Name
Research Site
City
Neuruppin
Country
Germany
Facility Name
Research Site
City
Basel
State/Province
Basel Stadt
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
20692140
Citation
Worth H, Forster K, Eriksson G, Nihlen U, Peterson S, Magnussen H. Budesonide added to formoterol contributes to improved exercise tolerance in patients with COPD. Respir Med. 2010 Oct;104(10):1450-9. doi: 10.1016/j.rmed.2010.07.006. Epub 2010 Aug 7.
Results Reference
derived
Learn more about this trial
Evaluation of Efficacy on Exercise Tolerance of Symbicort (Budesonide/Formoterol) Compared to Placebo and Oxis in Patients With Severe COPD
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