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Evaluation of Efficacy and Safety of Symbicort® as an add-on Treatment to Spiriva® in Patients With Severe COPD.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00496470
First received: July 3, 2007
Last updated: October 10, 2012
Last verified: October 2012
History of Changes
  Purpose

The purpose of this study is to investigate the effect of combined treatment with Symbicort and Spiriva, in terms of improvement of lung function, symptoms and inflammatory markers, in patients with severe COPD.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease, COPD
 Drug: Symbicort (budesonide/formoterol turbuhaler 320/9ug)
Drug: Spiriva (tiotropium bromide 18ug)
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 12-week, Double-blind, Randomised, Parallel Group, Multi-centre, Study to Evaluate Efficacy and Safety of Budesonide/Formoterol (Symbicort Turbuhaler®) 320/9 µg One Inhalation Twice Daily on Top of Tiotropium (Spiriva®) 18 µg One Inhalation Once Daily

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Forced Expiratory Volume in 1 Second (FEV1) Pre-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Change in the pre-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)


Secondary Outcome Measures:
  • Forced Expiratory Volume in 1 Second (FEV1) 5 Min Post-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Change in the 5 min post-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)

  • Forced Expiratory Volume in 1 Second (FEV1) 60 Min Post-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Change in the 60 min post-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)

  • Forced Vital Capacity (FVC) Pre-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Change in the pre-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)

  • Forced Vital Capacity (FVC) 5 Minutes Post-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Change in the 5 min post-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)

  • Forced Vital Capacity (FVC) 60 Minutes Post-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Change in the 60 min post-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12

  • Inspiratory Capacity (IC) Pre-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Change in the pre-dose IC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)

  • Inspiratory Capacity (IC) 60 Minutes Post-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Change in the 60 min post-dose IC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)

  • St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Score [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]

    Change in total score from baseline (Visit 3) to end of treatment (Visit 6, or last available visit).

    SGRQ-C is a health related quality of life questionnaire consisting of 40 items divided into two components: 1) symptoms, 2) activity& impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life.


  • Morning Peak Expiratory Flow (PEF) Pre-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record. Change in average values from run-in to the full treatment period

  • Evening Peak Expiratory Flow (PEF) Pre-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record. Change in average values from run-in to the full treatment period

  • Morning Peak Expiratory Flow (PEF) 5 Min Post-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record. Change in average values from run-in to the full treatment period

  • Morning Peak Expiratory Flow (PEF) 15 Min Post-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record. Change in average values from run-in to the full treatment period

  • Morning Diary FEV1 Pre-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record. Change in average values from run-in to the full treatment period

  • Evening Diary FEV1, Pre-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record. Change in average values from run-in to the full treatment period

  • Morning Diary FEV1, 5 Minutes Post-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record. Change in average values from run-in to the full treatment period

  • Morning Diary FEV1, 15 Minutes Post-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record. Change in average values from run-in to the full treatment period

  • Global Chest Symptoms Questionnaire (GCSQ) Score, Pre-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]

    Daily diary record. Change in average values from run-in to the full treatment period.

    The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions.


  • GCSQ Score, 5 Minutes Post-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]

    Daily diary record. Change in average values from run-in to the full treatment period.

    The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions.


  • GCSQ Score, 15 Minutes Post-dose [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]

    Daily diary record. Change in average values from run-in to the full treatment period.

    The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions.


  • Capacity of Day Living in the Morning (CDLM) Score [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]

    Daily diary record. Change in average values from run-in to the full treatment period.

    The CDLM questionnaire is as a questionnaire to report on patient's ability to carry out each of six different morning activities (score ranging from 0 "not performed" to 1"performed") and rank the difficulty of performing each of those activities (score ranging from 0 "so difficult that the activity could not be carried out by the patient on their own" to 5 "activity was not at all difficult to carry out". Total score for each morning activity range from 0-6. Total score for whole CDLM questionnaire range from 0-36.


  • Use of Rescue Medication, Night [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record - Night, after evening measurement till morning. Change in average values from run-in to the full treatment period

  • Use of Rescue Medication, Morning [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record - Morning, after morning measurement till midday. Change in average values from run-in to the full treatment period

  • Use of Rescue Medication, Day [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record - Day, after morning measurement till evening. Change in average values from run-in to the full treatment period

  • Use of Rescue Medication, Total [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record - Total, 24 hours, during the night, and during the day. Change in average values from run-in to the full treatment period

  • COPD Symptoms, Breathing Score [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe

  • COPD Symptoms, Sleeping Score [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe

  • COPD Symptoms, Chest Score [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe

  • COPD Symptoms, Cough Score [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe

  • Severe COPD Exacerbations [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Patients with worsening of COPD leading to treatment with systemic steroids (oral or parenteral), emergency room treatment or hospitalisation

  • Serum High-sensitivity C-reactive Protein (hsCRP) [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Ratio of treatment period mean to run-in value

  • Serum Interleukin 6 (IL-6) [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Ratio of treatment period mean to run-in value

  • Serum Interleukin 8 (IL-8) [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Ratio of treatment period mean to run-in value

  • Serum Monocyte Chemoattractant Protein-1 (MCP-1) [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Ratio of treatment period mean to run-in value

  • Serum Soluble Tumor Necrosis Factor-alpha (sTNF-alpha) [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Ratio of treatment period mean to run-in value

  • Serum Tumor Necrosis Factor-alpha (TNF-alpha) [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Ratio of treatment period mean to run-in value

  • Serum Vascular Cell Adhesion Molecule-1 (VCAM-1) [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Ratio of treatment period mean to run-in value


Enrollment: 660
Study Start Date: May 2007
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Symbicort+TIO
Symbicort Turbuhaler® (budesonide/formoterol) 320/9 mcg, one inhalation twice daily and Spiriva® (tiotropium) 18 mcg, one inhalation once daily
 Drug: Symbicort (budesonide/formoterol turbuhaler 320/9ug)
Symbicort (budesonide/formoterol turbuhaler 320/9ug)
Active Comparator: Spiriva® + Placebo Turbuhaler
Spiriva® (tiotropium) 18 mcg, one inhalation once daily and placebo Turbuhaler one inhalation once daily
 Drug: Spiriva (tiotropium bromide 18ug)
Spiriva (tiotropium bromide 18ug)

  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: NCT00496470

  Show 93 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Tomas Andersson, MD AstraZeneca R&D Lund
Principal Investigator: Tobias Welte, MD Hannover Medical School
  More Information

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00496470     History of Changes
Other Study ID Numbers: D5892C00015, Eudract no:2006-006796-21
Study First Received: July 3, 2007
Results First Received: June 15, 2009
Last Updated: October 10, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Poland: Ministry of Health
Slovakia: State Institute for Drug Control
Canada: Canadian Institutes of Health Research
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency

Keywords provided by AstraZeneca:
Chronic Obstructive Pulmonary Disease, COPD

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Bromides
Budesonide
Formoterol
Tiotropium
Symbicort
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
 Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
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 19, 2013