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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00489853
First received: June 19, 2007
Last updated: July 27, 2012
Last verified: July 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
 Drug: budesonide/formoterol Turbuhaler 320/9µg
Drug: formoterol Turbuhaler 9µg
Other: Placebo
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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).

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Exercise Endurance Time (EET) at 75% of Peak Work Capacity With Cycle Ergometry 1 Hour Post-dose [ Time Frame: Single measurement taken1 hour post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Single measurement taken 6 hours post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pre-dose at the start of treatment and pre-dose after one week of treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pre-dose at the start of treatment and pre-dose after one week of treatment ] [ Designated as safety issue: No ]
    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) [ Time Frame: Pre-dose at the start of treatment and pre-dose after one week of treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period ] [ Designated as safety issue: No ]
    The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period.

  • Sleep Score [ Time Frame: Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Single measurement performed after exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Single measurement performed after exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • Inspiratory Capacity (IC) Before Exercise Endurance Time (EET) Performed 6 Hours Post-dose [ Time Frame: Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • Vital Capacity (VC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET) [ Time Frame: Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET) [ Time Frame: Single measurement obtained before exercise endurance test performed 1hour post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET) [ Time Frame: Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • Residual Volume (RV) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET) [ Time Frame: Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET) [ Time Frame: Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET) [ Time Frame: Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • Vital Capacity (VC) (Body Plethysmography) Performed Before 6 Hour Exercise Endurance Time (EET) [ Time Frame: Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET) [ Time Frame: Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET) [ Time Frame: Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • Residual Volume (RV) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET) [ Time Frame: Single measurement obtained before exercise endurance test performed 6 hous post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET) [ Time Frame: Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 6 Hours Post-dose EET [ Time Frame: Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Treatment means from individual participant data.

  • SGRQ-C (St. George's Respiratory Questionnaire for COPD Patients) Total Score [ Time Frame: Single measurement taken at the end of each 1-week treatment period ] [ Designated as safety issue: No ]
    Score from a questionnaire, with scores ranging form 0 (perfect health) to 100 (worst possible state). Includes all patients with data.


Enrollment: 137
Study Start Date: July 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Symbicort then Formoterol then Placebo
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
Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms
Drug: formoterol Turbuhaler 9µg
Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily
Other: Placebo
Placebo, 1 inhalation twice daily
Experimental: Formoterol then Symbicort then Placebo
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
Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms
Drug: formoterol Turbuhaler 9µg
Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily
Other: Placebo
Placebo, 1 inhalation twice daily
Placebo Comparator: Placebo then Formoterol then Symbicort
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
Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms
Drug: formoterol Turbuhaler 9µg
Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily
Other: Placebo
Placebo, 1 inhalation twice daily

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00489853

Locations
Germany
Research Site
Berlin, Germany
Research Site
Erfurt, Germany
Research Site
Fulda, Germany
Research Site
Furth, Germany
Research Site
Geesthacht, Germany
Research Site
Grobhansdorf, Germany
Research Site
Leipzig, Germany
Research Site
Neuruppin, Germany
Switzerland
Research Site
Basel, Basel Stadt, Switzerland
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Tomas Andersson, MD AstraZeneca
Principal Investigator: Heinrich Worth, MD Akademisches Lehrkrankenhaus der Universität Erlangen-Nürnberg, Germany
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00489853     History of Changes
Other Study ID Numbers: D5892C00014, Eudract No: 2006-006519-60
Study First Received: June 19, 2007
Results First Received: August 6, 2009
Last Updated: July 27, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Switzerland: Swissmedic

Keywords provided by AstraZeneca:
COPD

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Budesonide
Formoterol
Symbicort
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
 Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 21, 2013