Efficacy and Tolerability of Symbicort as an add-on Treatment to Spiriva Compare With Spiriva Alone in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD) (SECURE 1)

A Randomised, Parallel-group, Open-label, Multicentre, 3-month Phase IV, Efficacy and Tolerability Study of Budesonide/Formoterol (Symbicort® Turbuhaler® 160/4.5μg/Inhalation, 2 Inhalations Twice Daily) Added to Tiotropium (SpirivaTM 18 μg/Inhalation, 1 Inhalation Once Daily) Compared With Tiotropium (SpirivaTM18 μg/Inhalation, 1 Inhalation Once Daily) Alone in Severe Chronic Obstructive Pulmonary Disease (COPD) Patients

This is a multicentre study with a randomised, parallel group, open-label, 3-month phase IV design to assess the efficacy and tolerability of Symbicort as an add-on treatment to Spiriva compare with Spiriva alone in patients with severe chronic obstructive pulmonary disease (COPD).

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: Budesonide/formoterol (Symbicort® Turbuhaler®); Drug: Tiotropium (SpirivaTM)

• Study Type: Interventional
• Enrollment (Actual): 793
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guang Zhou, China
    • Research Site
  • Beijing
    • Beijing, Beijing, China
      • Research Site
  • Guangdong
    • Guangzhou, Guangdong, China
      • Research Site
  • Hunan
    • Changsha, Hunan, China
      • Research Site
  • Jilin
    • Changchun, Jilin, China
      • Research Site
  • Liaoning
    • Shen Yang, Liaoning, China
      • Research Site
  • Shanghai
    • Shanghai, Shanghai, China
      • Research Site
  • Shanxi
    • Taiyuan, Shanxi, China
      • Research Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site
  • HK
    • Kowloon, HK, Hong Kong
      • Research Site
• Indonesia
  • Jakarta, Indonesia
    • Research Site
  • Solo, Indonesia
    • Research Site
  • Surabaya, Indonesia
    • Research Site
• Korea, Republic of
  • Busan, Korea, Republic of
    • Research Site
  • Daegu, Korea, Republic of
    • Research Site
  • Gwangju, Korea, Republic of
    • Research Site
  • Incheon, Korea, Republic of
    • Research Site
  • Seoul, Korea, Republic of
    • Research Site
  • Gangwon-do
    • Wonju-si, Gangwon-do, Korea, Republic of
      • Research Site
  • Gyeonggi-do
    • Suwon-si, Gyeonggi-do, Korea, Republic of
      • Research Site
  • Gyeongsangnam-do
    • Jinju-si, Gyeongsangnam-do, Korea, Republic of
      • Research Site
• Thailand
  • Bangkok, Thailand
    • Research Site
  • Chiang Mai, Thailand
    • Research Site
  • Chonburi, Thailand
    • Research Site
  • Khon Kaen, Thailand
    • Research Site
  • Nonthaburi, Thailand
    • Research Site
  • Phitsanulok, Thailand
    • Research Site
  • Songkhla, Thailand
    • Research Site
  • Udon Thani, Thailand
    • Research Site
  • NAN
    • Muang, NAN, Thailand
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed and dated informed consent
• Men or women patients ≥40 years of age
• Diagnosis of COPD with symptoms for more than 2 years and there is a history of at least one COPD exacerbation requiring a course of oral steroids and/or antibiotics within 1-12 months before Visit 2
• Forced Expiratory Volume in 1 second (FEV1) ≤50% of predicted normal value, pre-bronchodilator and Forced Expiratory Volume in 1 second (FEV1) / Forced Vital Capacity (FVC) < 70%, pre-bronchodilator
• Total symptom score of 2 or more per day for at least half of run-in period (breathing, cough and sputum scores from the diary card) and complete morning recordings of Digital Peak Flow Meter data at least 7 out of the last 10 days of the run-in period

Exclusion Criteria:

• A history of asthma and seasonal allergic rhinitis before 40 years of age
• Patients who have experienced exacerbation of COPD requiring hospitalisation and /or emergency room treatment and/or a course of oral steroids and/or intravenous corticosteroids and/or antibiotics within 4 weeks prior to Visit 2 and/or during run-in period and also the patients who use of systemic glucocorticosteroids (GCS) within 4 weeks and/or inhaled GCS within 2 weeks prior to Visit 2 and/or during run-in period
• Patients with relevant cardiovascular disorder judged by the investigator
• Patients with glaucoma, prostatic hyperplasia or bladder-neck obstruction judged by the investigator
• Women who are pregnant, breast-feeding or of child-bearing potential judged by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1; Add-on treatment	Drug: Budesonide/formoterol (Symbicort® Turbuhaler®); Budesonide/formoterol (Symbicort® Turbuhaler®) 160/4.5μg/inhalation, 2 inhalations twice daily; Drug: Tiotropium (SpirivaTM); Tiotropium (SpirivaTM) 18 μg/inhalation, 1 inhalation once daily
Other: 2; Add-on treatment	Drug: Tiotropium (SpirivaTM); Tiotropium (SpirivaTM) 18 μg/inhalation, 1 inhalation once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-dose FEV1	Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value	Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-dose FEV1 at 5 Minutes	Ratio of post-dose FEV1 at 5 minutes to baseline value	Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drug
Post-dose FEV1 at 60 Minutes	Ratio of post-dose FEV1 at 60 minutes to baseline value	Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
Pre-dose FVC	Ratio of pre-dose FVC (Forced Vital Capacity) in treatment period to baseline value	Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
Post-dose FVC at 5 Minutes	Ratio of post-dose FVC at 5 minutes to baseline value	Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 5 minutes after inhalation of study drug at weeks 0, 1, 6, 12)
Post-dose FVC at 60 Minutes	Ratio of post-dose FVC at 60 minutes to baseline value	Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
Pre-dose IC	Ratio of pre-dose IC (Inspiratory Capacity) in treatment period to baseline value	Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
Post-dose IC at 60 Minutes	Ratio of post-dose IC at 60 minutes to baseline value	Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
Pre-dose PEF in Last Week of Treatment	Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to last week of treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the last week of treatment, up to 12 weeks
Pre-dose PEF in First Week of Treatment	Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to first week of treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the first week of treatment
Pre-dose PEF in Whole Treatment Period	Change in pre-dose morning PEF from run-in period to whole treatment period	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in whole treatment period of 12 weeks
Post-dose PEF in Last Week of Treatment	Change in post-dose morning PEF at 5 minutes from run-period to last week of treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the last week of treatment, up to 12 weeks
Post-dose PEF in First Week of Treatment	Change in post-dose morning PEF at 5 minutes from run-in period to first week of treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the first week of treatment
Post-dose PEF in Whole Treatment Period	Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in whole treatment period of 12 weeks
Use of Reliever Medication During Day in the Last Week on Treatment	Change in the number of inhalations of reliever medication during day from run-in period to the last week on treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment, up to 12 weeks
Use of Reliever Medication During Day in the First Week on Treatment	Change in the number of inhalations of reliever medication during day from run-in period to the first week on treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the first week on treatment
Use of Reliever Medication During Day in the Whole Treatment Period	Change in the number of inhalations of reliever medication during day from run-in period to the whole treatment period	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period of 12 weeks
Use of Reliever Medication During Night in the Last Week on Treatment	Change in the number of inhalations of reliever medication during night from run-in period to the last week on treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment, up to 12 weeks
Use of Reliever Medication During Night in the First Week on Treatment	Change in the number of inhalations of reliever medication during day from run-in period to the first week on treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the first week on treatment
Use of Reliever Medication During Night in the Whole Treatment Period	Change in the number of inhalations of reliever medication during night from run-in period to the whole treatment period	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period of 12 weeks
Change in COPD Symptoms - Breathing	Change in breathing symptom score (from 0:none to 4:severe) from run-in period	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks
Change in COPD Symptoms - Cough	Change in Cough symptom score (from 0:none to 4:severe) from run-in period	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks
Change in COPD Symptoms - Sputum	Change in Sputum symptom score (from 0:none to 4:severe) from run-in period	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks
COPD Exacerbations	Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms	Whole treatment period of 12 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Chair: Samuel Chen, M.D., AstraZeneca Pharmaceutical Co., Ltd., Shanghai, China

Publications and helpful links

General Publications

• Lee SD, Xie CM, Yunus F, Itoh Y, Ling X, Yu WC, Kiatboonsri S. Efficacy and tolerability of budesonide/formoterol added to tiotropium compared with tiotropium alone in patients with severe or very severe COPD: A randomized, multicentre study in East Asia. Respirology. 2016 Jan;21(1):119-27. doi: 10.1111/resp.12646. Epub 2015 Sep 23.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: June 27, 2011
• First Submitted That Met QC Criteria: July 19, 2011
• First Posted (Estimate): July 20, 2011

Study Record Updates

• Last Update Posted (Estimate): March 27, 2015
• Last Update Submitted That Met QC Criteria: March 25, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Severe chronic obstructive pulmonary disease (COPD) patients
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Budesonide; Tiotropium Bromide; Formoterol Fumarate; Budesonide, Formoterol Fumarate Drug Combination
• Other Study ID Numbers: D589BL00023