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

Chronic Obstructive Pulmonary Disease, COPD Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00496470
• Other study ID #: D5892C00015
• Secondary ID: Eudract no:2006-
• Status: Completed
• Phase: Phase 4
• First received: July 3, 2007
• Last updated: October 10, 2012
• Start date: May 2007
• Est. completion date: June 2008

Study information

• Verified date: October 2012
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyPoland: Ministry of HealthSlovakia: State Institute for Drug ControlCanada: Canadian Institutes of Health ResearchSpain: Spanish Agency of MedicinesSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 660
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease, COPD
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Symbicort (budesonide/formoterol turbuhaler 320/9ug)
Symbicort (budesonide/formoterol turbuhaler 320/9ug)
• Spiriva (tiotropium bromide 18ug)
Spiriva (tiotropium bromide 18ug)

Locations

Country	Name	City	State
Australia	Research Site	Adelaide	South Australia
Australia	Research Site	Auchenflower	Queensland
Australia	Research Site	Carina Heights	Queensland
Australia	Research Site	Clayton	Victoria
Australia	Research Site	Concord	New South Wales
Australia	Research Site	Daw Park	South Australia
Australia	Research Site	Malvern	Victoria
Australia	Research Site	Nedlands	Western Australia
Australia	Research Site	North Mackay	Queensland
Australia	Research Site	Sydney	New South Wales
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	La Malbaie	Quebec
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Research Site	St. John's	Newfoundland and Labrador
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Trois-rivires	Quebec
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Winnipeg	Manitoba
France	Research Site	Chamalieres
France	Research Site	Creil
France	Research Site	Ferolles Attilly
France	Research Site	Grasse
France	Research Site	Lille
France	Research Site	Marseille Cedex 06
France	Research Site	Metz
France	Research Site	Montpellier
France	Research Site	Perpignan
France	Research Site	Poitiers Cedex
France	Research Site	Selestat
France	Research Site	St Laurent Du Var
France	Research Site	Strasbourg Cedex
France	Research Site	Toulouse Cedex 9
Germany	Research Site	Berlin
Germany	Research Site	Gelsenkirchen
Germany	Research Site	Hagen
Germany	Research Site	Hannover
Germany	Research Site	Kassel
Germany	Research Site	Koblenz
Germany	Research Site	Leipzig
Germany	Research Site	Marburg
Germany	Research Site	Potsdam
Hungary	Research Site	Aszod
Hungary	Research Site	Baja
Hungary	Research Site	Balassagyarmat
Hungary	Research Site	Budapest
Hungary	Research Site	Cegled
Hungary	Research Site	Debrecen
Hungary	Research Site	Fuzesabony
Hungary	Research Site	Jaszbereny
Hungary	Research Site	Komlo
Hungary	Research Site	Nyiregyhaza
Hungary	Research Site	Torokbalint
Hungary	Research Site	Vásárosnamény
Poland	Research Site	Bydgoszcz
Poland	Research Site	Chrzanów
Poland	Research Site	Ilawa
Poland	Research Site	Krakow
Poland	Research Site	Lomza
Poland	Research Site	Piekary Slaskie
Poland	Research Site	Tarnow
Poland	Research Site	Turek
Poland	Research Site	Zawadzkie
Slovakia	Research Site	Kosice
Slovakia	Research Site	Liptovsky Hradok
Slovakia	Research Site	Lucenec
Slovakia	Research Site	Nove Mesto Nad Vahom
Slovakia	Research Site	Nove Zamky
Slovakia	Research Site	Piestany
Slovakia	Research Site	Poprad
Slovakia	Research Site	Povazska Bystrica
Slovakia	Research Site	Presov
Slovakia	Research Site	Prievidza
Slovakia	Research Site	Revuca
Slovakia	Research Site	Trnava
Slovakia	Research Site	Zilina
Spain	Research Site	Barcelona	Cataluna
Spain	Research Site	Madrid	Comunidad de Madrid
Spain	Research Site	Pontevedra	Galicia
Spain	Research Site	Requena (valencia)	Comunidad Valenciana
Spain	Research Site	Reus (tarragona)	Cataluna
Spain	Research Site	Valencia	Comunidad Valenciana
Sweden	Research Site	Atvidaberg
Sweden	Research Site	Hollviken
Sweden	Research Site	Limhamn
Sweden	Research Site	Lindesberg	Orebro Lan
Sweden	Research Site	Lund
Sweden	Research Site	Malmo
Sweden	Research Site	Motala
Sweden	Research Site	Stockholm
Sweden	Research Site	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Australia,  Canada,  France,  Germany,  Hungary,  Poland,  Slovakia,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forced Expiratory Volume in 1 Second (FEV1) Pre-dose	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)	Baseline to 12 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) 5 Min Post-dose	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)	Baseline to 12 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) 60 Min Post-dose	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)	Baseline to 12 weeks	No
Secondary	Forced Vital Capacity (FVC) Pre-dose	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)	Baseline to 12 weeks	No
Secondary	Forced Vital Capacity (FVC) 5 Minutes Post-dose	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)	Baseline to 12 weeks	No
Secondary	Forced Vital Capacity (FVC) 60 Minutes Post-dose	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	Baseline to 12 weeks	No
Secondary	Inspiratory Capacity (IC) Pre-dose	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)	Baseline to 12 weeks	No
Secondary	Inspiratory Capacity (IC) 60 Minutes Post-dose	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)	Baseline to 12 weeks	No
Secondary	St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Score	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.	Baseline and 12 weeks	No
Secondary	Morning Peak Expiratory Flow (PEF) Pre-dose	Daily diary record. Change in average values from run-in to the full treatment period	Baseline to 12 weeks	No
Secondary	Evening Peak Expiratory Flow (PEF) Pre-dose	Daily diary record. Change in average values from run-in to the full treatment period	Baseline to 12 weeks	No
Secondary	Morning Peak Expiratory Flow (PEF) 5 Min Post-dose	Daily diary record. Change in average values from run-in to the full treatment period	Baseline to 12 weeks	No
Secondary	Morning Peak Expiratory Flow (PEF) 15 Min Post-dose	Daily diary record. Change in average values from run-in to the full treatment period	Baseline to 12 weeks	No
Secondary	Morning Diary FEV1 Pre-dose	Daily diary record. Change in average values from run-in to the full treatment period	Baseline to 12 weeks	No
Secondary	Evening Diary FEV1, Pre-dose	Daily diary record. Change in average values from run-in to the full treatment period	Baseline to 12 weeks	No
Secondary	Morning Diary FEV1, 5 Minutes Post-dose	Daily diary record. Change in average values from run-in to the full treatment period	Baseline to 12 weeks	No
Secondary	Morning Diary FEV1, 15 Minutes Post-dose	Daily diary record. Change in average values from run-in to the full treatment period	Baseline to 12 weeks	No
Secondary	Global Chest Symptoms Questionnaire (GCSQ) Score, Pre-dose	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.	Baseline to 12 weeks	No
Secondary	GCSQ Score, 5 Minutes Post-dose	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.	Baseline to 12 weeks	No
Secondary	GCSQ Score, 15 Minutes Post-dose	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.	Baseline to 12 weeks	No
Secondary	Capacity of Day Living in the Morning (CDLM) Score	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.	Baseline to 12 weeks	No
Secondary	Use of Rescue Medication, Night	Daily diary record - Night, after evening measurement till morning. Change in average values from run-in to the full treatment period	Baseline to 12 weeks	No
Secondary	Use of Rescue Medication, Morning	Daily diary record - Morning, after morning measurement till midday. Change in average values from run-in to the full treatment period	Baseline to 12 weeks	No
Secondary	Use of Rescue Medication, Day	Daily diary record - Day, after morning measurement till evening. Change in average values from run-in to the full treatment period	Baseline to 12 weeks	No
Secondary	Use of Rescue Medication, Total	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	Baseline to 12 weeks	No
Secondary	COPD Symptoms, Breathing Score	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	Baseline to 12 weeks	No
Secondary	COPD Symptoms, Sleeping Score	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	Baseline to 12 weeks	No
Secondary	COPD Symptoms, Chest Score	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	Baseline to 12 weeks	No
Secondary	COPD Symptoms, Cough Score	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	Baseline to 12 weeks	No
Secondary	Severe COPD Exacerbations	Patients with worsening of COPD leading to treatment with systemic steroids (oral or parenteral), emergency room treatment or hospitalisation	12 weeks	No
Secondary	Serum High-sensitivity C-reactive Protein (hsCRP)	Ratio of treatment period mean to run-in value	Baseline to 12 weeks	No
Secondary	Serum Interleukin 6 (IL-6)	Ratio of treatment period mean to run-in value	Baseline to 12 weeks	No
Secondary	Serum Interleukin 8 (IL-8)	Ratio of treatment period mean to run-in value	Baseline to 12 weeks	No
Secondary	Serum Monocyte Chemoattractant Protein-1 (MCP-1)	Ratio of treatment period mean to run-in value	Baseline to 12 weeks	No
Secondary	Serum Soluble Tumor Necrosis Factor-alpha (sTNF-alpha)	Ratio of treatment period mean to run-in value	Baseline to 12 weeks	No
Secondary	Serum Tumor Necrosis Factor-alpha (TNF-alpha)	Ratio of treatment period mean to run-in value	Baseline to 12 weeks	No
Secondary	Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)	Ratio of treatment period mean to run-in value	Baseline to 12 weeks	No