Clinical trial NCT01397890: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: Severe chronic obstructive pulmonary disease (COPD) patients
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-07-20
Enrollment: 793
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Pre-dose FEV1
timeFrame: Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
Secondary outcomes:
measure: Post-dose FEV1 at 5 Minutes
timeFrame: Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drug
measure: Post-dose FEV1 at 60 Minutes
timeFrame: 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)
measure: Pre-dose FVC
timeFrame: 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)
measure: Post-dose FVC at 5 Minutes
timeFrame: 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)
measure: Post-dose FVC at 60 Minutes
timeFrame: 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)
measure: Pre-dose IC
timeFrame: Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
measure: Post-dose IC at 60 Minutes
timeFrame: 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)
measure: Pre-dose PEF in Last Week of Treatment
timeFrame: 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
measure: Pre-dose PEF in First Week of Treatment
timeFrame: 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
measure: Pre-dose PEF in Whole Treatment Period
timeFrame: 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
measure: Post-dose PEF in Last Week of Treatment
timeFrame: 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
measure: Post-dose PEF in First Week of Treatment
timeFrame: 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
measure: Post-dose PEF in Whole Treatment Period
timeFrame: 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
measure: Use of Reliever Medication During Day in the Last Week on Treatment
timeFrame: 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
measure: Use of Reliever Medication During Day in the First Week on Treatment
timeFrame: 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
measure: Use of Reliever Medication During Day in the Whole Treatment Period
timeFrame: 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
measure: Use of Reliever Medication During Night in the Last Week on Treatment
timeFrame: 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
measure: Use of Reliever Medication During Night in the First Week on Treatment
timeFrame: 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
measure: Use of Reliever Medication During Night in the Whole Treatment Period
timeFrame: 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
measure: Change in COPD Symptoms - Breathing
timeFrame: 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
measure: Change in COPD Symptoms - Cough
timeFrame: 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
measure: Change in COPD Symptoms - Sputum
timeFrame: 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
measure: COPD Exacerbations
timeFrame: Whole treatment period of 12 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
state: Beijing
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Changsha
country: China
facility: Research Site
state: Hunan
city: Changchun
country: China
facility: Research Site
state: Jilin
city: Shen Yang
country: China
facility: Research Site
state: Liaoning
city: Shanghai
country: China
facility: Research Site
state: Shanghai
city: Taiyuan
country: China
facility: Research Site
state: Shanxi
city: Guang Zhou
country: China
facility: Research Site
city: Kowloon
country: Hong Kong
facility: Research Site
state: HK
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Jakarta
country: Indonesia
facility: Research Site
city: Solo
country: Indonesia
facility: Research Site
city: Surabaya
country: Indonesia
facility: Research Site
city: Wonju-si
country: Korea, Republic of
facility: Research Site
state: Gangwon-do
city: Suwon-si
country: Korea, Republic of
facility: Research Site
state: Gyeonggi-do
city: Jinju-si
country: Korea, Republic of
facility: Research Site
state: Gyeongsangnam-do
city: Busan
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Muang
country: Thailand
facility: Research Site
state: NAN
city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Chonburi
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Nonthaburi
country: Thailand
facility: Research Site
city: Phitsanulok
country: Thailand
facility: Research Site
city: Songkhla
country: Thailand
facility: Research Site
city: Udon Thani
country: Thailand
facility: Research Site
Study officials:
affiliation: AstraZeneca Pharmaceutical Co., Ltd., Shanghai, China
name: Samuel Chen, M.D.
role: STUDY_CHAIR
References:
citation: 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.