Comparing the Efficacy of Symbicort® pMDI and Formoterol Turbuhaler in Reducing Exacerbations in Patients With Cronic Obstructive Pulmonary Disease

COPD Patients Clinical Trial

— RISE  

Official title:

A Phase IIIB, 6-Month, Double-blind, Double-dummy, Randomized, Parallel-group, Multicenter Exacerbation Study of Symbicort® Pressurized Metered-Dose Inhaler (pMDI) 160/4.5 μg x 2 Actuations Twice-daily Compared to Formoterol Turbuhaler 4.5 μg x 2 Inhalations Twice-daily in Cronic Obstructive Pulmonary Disease (COPD) Patients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02157935
• Other study ID #: D589UC00001
• Status: Completed
• Phase: Phase 3
• First received: June 5, 2014
• Last updated: October 5, 2017
• Start date: June 27, 2014
• Est. completion date: February 8, 2016

Study information

• Verified date: October 2017
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Comparing the efficacy of Symbicort® pMDI and Formoterol Turbuhaler in reducing exacerbations in patients with Chronic Obstructive Pulmonary Disease (COPD).

Description:

A Phase IIIB, 6-Month, Double-blind, Double-dummy, Randomized, Parallel-group, Multicenter Exacerbation Study of Symbicort® pMDI 160/4.5 μg x 2 Actuations Twice-daily Compared to Formoterol Turbuhaler 4.5 μg x 2 Inhalations Twice-daily in COPD Patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2026
• Est. completion date: February 8, 2016
• Est. primary completion date: February 8, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 95 Years

Eligibility

Inclusion Criteria:

3. A current clinical diagnosis of COPD with COPD symptoms for more than 1 year, according to the GOLD guidelines.

4. Current or previous smoker with a smoking history equivalent to 10 or more pack years (1 pack year = 20 cigarettes smoked per day for 1 year).

5. Post-bronchodilator FEV1/forced vital capacity (FVC) <0.7 (70%) and FEV1 =70% of predicted normal (PN) value.

6. Documented use of a short-acting inhaled bronchodilator (ß2-agonists or anticholinergics) as rescue medication within 6 months prior to study start.

7. A score of =2 on the modified medical research council (MMRC) dyspnea scale. 8. Documented history of =1 moderate or severe COPD exacerbation(s) that required treatment with systemic (oral, IM, IV) corticosteroids (a minimum 3 day course of an oral corticosteroid treatment or single depot corticosteroid injection), or hospitalization (defined as an inpatient stay or >24 hour stay in an observation area in the emergency department or other equivalent facility depending on the country and healthcare system) within 2-52 weeks before Visit 1 (i.e., not within the 14 days prior to Visit 1). A history of an exacerbation treated exclusively with antibiotics will not be considered adequate.

Exclusion Criteria:

1. A history of asthma at or after 18 years of age.

2. Subjects with significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure (including significant cor pulmonale), uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator.

3. Known homozygous alpha-1 antitrypsin deficiency.

4. Any significant disease or disorder (e.g., gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results of the study, or the subject's ability to participate in the study.

5. A history of malignancy (except basal cell carcinoma) within the past 5 years.

6. Active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung disease, or other active pulmonary diseases.

7. Subjects who have needed additions or alterations to their usual maintenance or change in formulation of rescue therapy for COPD due to worsening symptoms within the 14 days prior to Visit 1 and up to Visit 3.

8. CXR (frontal and lateral) with suspicion of pneumonia or other condition/abnormality that will require additional investigation/treatment, or put the subject at risk because of participation in the study.

9. Risk factors for pneumonia: immune suppression (HIV, lupus) or other risk for pneumonia (e.g. neurological disorders affecting control of the upper airway, such as Parkinson's disease, myasthenia gravis, etc.).

10. Pneumonia not resolved within 14 days of Visit 1.

11. Moderate or severe COPD exacerbation that has not resolved within 14 days prior to Visit 1 or a moderate or severe COPD exacerbation that occurs between Visit 1 and Visit 2.

12. Long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day.

13. Subjects who are currently in the intensive rehabilitation phase or scheduled to begin new participation (intensive rehabilitation phase) in a pulmonary rehabilitation program during the study or have started a new pulmonary rehabilitation program within 60 days of Visit 1. Subjects in the maintenance phase of pulmonary rehabilitation program are not excluded.

14. Treatment with oral, parenteral, or intra-articular corticosteroids within 4 weeks prior to Visit 1.

15. Omalizumab or any other monoclonal or polyclonal antibody therapy taken for any reason within 6 months prior to Visit 1.

Related Conditions & MeSH terms

• COPD Patients
• Lung Diseases
• Lung Diseases, Obstructive

Intervention

Drug:
• Symbicort
Budesonide/formoterol pMDI, 160/4.5 µg x 2 actuations BID, for oral inhalation, 120 doses
• Formoterol turbohaler
Formoterol Turbuhaler 4.5 µg x 2 actuations BID, for oral inhalation, 60 doses

Other:
• Placebo for Symbicort pMDI
pMDI, aerosol for oral inhalation, placebo, 120 doses
• Placebo for Formoterol Turbohaler
PLacebo powder for oral inhalation, 60 doses

Locations

Country	Name	City	State
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Córdoba
Argentina	Research Site	Córdoba
Argentina	Research Site	Corrientes
Argentina	Research Site	Corrientes
Argentina	Research Site	Mendoza
Argentina	Research Site	Mendoza
Argentina	Research Site	Nueve de julio
Argentina	Research Site	Nueve de julio
Argentina	Research Site	Ranelagh
Argentina	Research Site	Ranelagh
Argentina	Research Site	San Miguel de Tucuman
Argentina	Research Site	San Miguel de Tucuman
Bulgaria	Research Site	Dupnitsa
Bulgaria	Research Site	Dupnitsa
Bulgaria	Research Site	Gotse Delchev
Bulgaria	Research Site	Gotse Delchev
Bulgaria	Research Site	Kozloduy
Bulgaria	Research Site	Kozloduy
Bulgaria	Research Site	Pazardzhik
Bulgaria	Research Site	Pazardzhik
Bulgaria	Research Site	Sandanski
Bulgaria	Research Site	Sandanski
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Varna
Bulgaria	Research Site	Varna
Bulgaria	Research Site	Varna
Bulgaria	Research Site	Veliko Tarnovo
Bulgaria	Research Site	Veliko Tarnovo
Bulgaria	Research Site	Velingrad
Bulgaria	Research Site	Velingrad
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Czechia	Research Site	Beroun
Czechia	Research Site	Beroun
Czechia	Research Site	Brandys nad Labem
Czechia	Research Site	Brandys nad Labem
Czechia	Research Site	Krnov
Czechia	Research Site	Krnov
Czechia	Research Site	Liberec
Czechia	Research Site	Liberec
Czechia	Research Site	Ostrava
Czechia	Research Site	Ostrava
Czechia	Research Site	Ostrava-Poruba
Czechia	Research Site	Ostrava-Poruba
Czechia	Research Site	Praha 10
Czechia	Research Site	Praha 10
Czechia	Research Site	Praha 5
Czechia	Research Site	Praha 5
Czechia	Research Site	Praha 5
Czechia	Research Site	Praha 6
Czechia	Research Site	Praha 6
Czechia	Research Site	Strakonice
Czechia	Research Site	Strakonice
Czechia	Research Site	Zatec
Czechia	Research Site	Zatec
Germany	Research Site	Aschaffenburg
Germany	Research Site	Aschaffenburg
Germany	Research Site	Bad Lippspringe
Germany	Research Site	Bad Lippspringe
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Hannover
Germany	Research Site	Hannover
Germany	Research Site	Koblenz
Germany	Research Site	Koblenz
Germany	Research Site	Köln
Germany	Research Site	Köln
Germany	Research Site	Leipzig
Germany	Research Site	Leipzig
Germany	Research Site	Leipzig
Germany	Research Site	Magdeburg
Germany	Research Site	Magdeburg
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico
Mexico	Research Site	Mexico
Mexico	Research Site	Monterrey
Mexico	Research Site	Monterrey
Mexico	Research Site	San Juan del Rio
Mexico	Research Site	San Juan del Rio
Mexico	Research Site	Sonora
Mexico	Research Site	Sonora
Poland	Research Site	Aleksandrów Lódzki
Poland	Research Site	Aleksandrów Lódzki
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Bielsk Podlaski
Poland	Research Site	Bielsk Podlaski
Poland	Research Site	Bydgoszcz
Poland	Research Site	Bydgoszcz
Poland	Research Site	Koscian
Poland	Research Site	Koscian
Poland	Research Site	Kraków
Poland	Research Site	Kraków
Poland	Research Site	Lublin
Poland	Research Site	Lublin
Poland	Research Site	Ostrowiec Swietokrzyski
Poland	Research Site	Ostrowiec Swietokrzyski
Poland	Research Site	Pila
Poland	Research Site	Pila
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Rzeszów
Poland	Research Site	Rzeszów
Poland	Research Site	Skarzysko-Kamienna
Poland	Research Site	Skarzysko-Kamienna
Poland	Research Site	Turek
Poland	Research Site	Turek
Poland	Research Site	Zabrze
Poland	Research Site	Zabrze
Poland	Research Site	Znin
Poland	Research Site	Znin
Puerto Rico	Research Site	San Juan
Puerto Rico	Research Site	San Juan
South Africa	Research Site	Amanzimtoti
South Africa	Research Site	Amanzimtoti
South Africa	Research Site	Cape Town
South Africa	Research Site	Cape Town
South Africa	Research Site	Cape Town
South Africa	Research Site	Cape Town
South Africa	Research Site	Durban
South Africa	Research Site	Durban
South Africa	Research Site	Durban
South Africa	Research Site	Gauteng
South Africa	Research Site	Gauteng
Spain	Research Site	Badalona(Barcelona)
Spain	Research Site	Badalona(Barcelona)
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Loja (Granada)
Spain	Research Site	Loja (Granada)
Spain	Research Site	Zaragoza
Spain	Research Site	Zaragoza
United States	Research Site	Andalusia	Alabama
United States	Research Site	Andalusia	Alabama
United States	Research Site	Anderson	South Carolina
United States	Research Site	Anderson	South Carolina
United States	Research Site	Atlanta	Georgia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Aurora	Colorado
United States	Research Site	Avon	Indiana
United States	Research Site	Avon	Indiana
United States	Research Site	Bangor	Maine
United States	Research Site	Bangor	Maine
United States	Research Site	Bellevue	Nebraska
United States	Research Site	Bellevue	Nebraska
United States	Research Site	Billings	Montana
United States	Research Site	Billings	Montana
United States	Research Site	Biloxi	Mississippi
United States	Research Site	Biloxi	Mississippi
United States	Research Site	Birmingham	Alabama
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boerne	Texas
United States	Research Site	Boerne	Texas
United States	Research Site	Brockton	Massachusetts
United States	Research Site	Brockton	Massachusetts
United States	Research Site	Brownsburg	Indiana
United States	Research Site	Brownsburg	Indiana
United States	Research Site	Cadiz	Ohio
United States	Research Site	Cadiz	Ohio
United States	Research Site	Chandler	Arizona
United States	Research Site	Chandler	Arizona
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Clearwater	Florida
United States	Research Site	Clearwater	Florida
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Columbus	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Coral Gables	Florida
United States	Research Site	Coral Gables	Florida
United States	Research Site	Cornelius	North Carolina
United States	Research Site	Cornelius	North Carolina
United States	Research Site	Council Bluffs	Iowa
United States	Research Site	Council Bluffs	Iowa
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Eagle	Idaho
United States	Research Site	Eagle	Idaho
United States	Research Site	Easley	South Carolina
United States	Research Site	Easley	South Carolina
United States	Research Site	El Paso	Texas
United States	Research Site	El Paso	Texas
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Flagstaff	Arizona
United States	Research Site	Flagstaff	Arizona
United States	Research Site	Flat Rock	North Carolina
United States	Research Site	Flat Rock	North Carolina
United States	Research Site	Foley	Alabama
United States	Research Site	Foley	Alabama
United States	Research Site	Fort Lauderdale	Florida
United States	Research Site	Fort Lauderdale	Florida
United States	Research Site	Fort Mitchell	Kentucky
United States	Research Site	Fort Mitchell	Kentucky
United States	Research Site	Fresno	California
United States	Research Site	Fresno	California
United States	Research Site	Fullerton	California
United States	Research Site	Fullerton	California
United States	Research Site	Genoa	Ohio
United States	Research Site	Genoa	Ohio
United States	Research Site	Gold River	California
United States	Research Site	Gold River	California
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Hazard	Kentucky
United States	Research Site	Hazard	Kentucky
United States	Research Site	Herndon	Virginia
United States	Research Site	Herndon	Virginia
United States	Research Site	Hialeah	Florida
United States	Research Site	Hialeah	Florida
United States	Research Site	High Point	North Carolina
United States	Research Site	High Point	North Carolina
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Indian Land	South Carolina
United States	Research Site	Indian Land	South Carolina
United States	Research Site	Jackson Heights	New York
United States	Research Site	Jackson Heights	New York
United States	Research Site	Jasper	Alabama
United States	Research Site	Jasper	Alabama
United States	Research Site	Jefferson Hills	Pennsylvania
United States	Research Site	Jefferson Hills	Pennsylvania
United States	Research Site	Kingwood	West Virginia
United States	Research Site	Kingwood	West Virginia
United States	Research Site	Kissimmee	Florida
United States	Research Site	Kissimmee	Florida
United States	Research Site	Lakewood	California
United States	Research Site	Lakewood	California
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Marion	Ohio
United States	Research Site	Marion	Ohio
United States	Research Site	Marlton	New Jersey
United States	Research Site	Marlton	New Jersey
United States	Research Site	Maumee	Ohio
United States	Research Site	Maumee	Ohio
United States	Research Site	McKinney	Texas
United States	Research Site	McKinney	Texas
United States	Research Site	Medford	Oregon
United States	Research Site	Medford	Oregon
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Midvale	Utah
United States	Research Site	Midvale	Utah
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Mobile	Alabama
United States	Research Site	Mobile	Alabama
United States	Research Site	Muncie	Indiana
United States	Research Site	Muncie	Indiana
United States	Research Site	Myrtle Beach	South Carolina
United States	Research Site	Myrtle Beach	South Carolina
United States	Research Site	Nampa	Idaho
United States	Research Site	Nampa	Idaho
United States	Research Site	Newport Beach	California
United States	Research Site	Newport Beach	California
United States	Research Site	Newport News	Virginia
United States	Research Site	Newport News	Virginia
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Omaha	Nebraska
United States	Research Site	Omaha	Nebraska
United States	Research Site	Opelousas	Louisiana
United States	Research Site	Opelousas	Louisiana
United States	Research Site	Orange	California
United States	Research Site	Orange	California
United States	Research Site	Orlando	Florida
United States	Research Site	Orlando	Florida
United States	Research Site	Ormond Beach	Florida
United States	Research Site	Ormond Beach	Florida
United States	Research Site	Panama City	Florida
United States	Research Site	Panama City	Florida
United States	Research Site	Pensacola	Florida
United States	Research Site	Pensacola	Florida
United States	Research Site	Peoria	Arizona
United States	Research Site	Peoria	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Plano	Texas
United States	Research Site	Plano	Texas
United States	Research Site	Plymouth	Minnesota
United States	Research Site	Plymouth	Minnesota
United States	Research Site	Port Huron	Michigan
United States	Research Site	Port Huron	Michigan
United States	Research Site	Port Orange	Florida
United States	Research Site	Port Orange	Florida
United States	Research Site	Portland	Oregon
United States	Research Site	Portland	Oregon
United States	Research Site	Rancho Mirage	California
United States	Research Site	Rancho Mirage	California
United States	Research Site	Richmond	Virginia
United States	Research Site	Richmond	Virginia
United States	Research Site	Rincon	Georgia
United States	Research Site	Rincon	Georgia
United States	Research Site	Rochester	New York
United States	Research Site	Rochester	New York
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Jose	California
United States	Research Site	San Jose	California
United States	Research Site	Sarasota	Florida
United States	Research Site	Sarasota	Florida
United States	Research Site	Scottdale	Pennsylvania
United States	Research Site	Scottdale	Pennsylvania
United States	Research Site	Sealy	Texas
United States	Research Site	Sealy	Texas
United States	Research Site	Sebring	Florida
United States	Research Site	Sebring	Florida
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Springfield	Illinois
United States	Research Site	Springfield	Illinois
United States	Research Site	Stockbridge	Georgia
United States	Research Site	Stockbridge	Georgia
United States	Research Site	Summit	New Jersey
United States	Research Site	Summit	New Jersey
United States	Research Site	Sunset	Louisiana
United States	Research Site	Sunset	Louisiana
United States	Research Site	Tacoma	Washington
United States	Research Site	Tacoma	Washington
United States	Research Site	Tucson	Arizona
United States	Research Site	Tucson	Arizona
United States	Research Site	Uniontown	Pennsylvania
United States	Research Site	Uniontown	Pennsylvania
United States	Research Site	Valparaiso	Indiana
United States	Research Site	Valparaiso	Indiana
United States	Research Site	Westminster	California
United States	Research Site	Westminster	California
United States	Research Site	Willoughby	Ohio
United States	Research Site	Willoughby	Ohio
United States	Research Site	Winter Park	Florida
United States	Research Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Chile,  Czechia,  Germany,  Mexico,  Poland,  Puerto Rico,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Rate of Moderate and Severe COPD Exacerbations Defined as: Worsening of =2 Major Symptoms or Worsening of 1 Major Symptom Together With =1 Minor Symptom for =2 Consecutive Days	The annual COPD exacerbation rate was analyzed and compared between two arms.; Annual exacerbation rate for each subject is defined as number of exacerbations divided by duration of randomized treatment period in years.; The annual COPD exacerbation rate of Symbicort group was compared with annual rate of Formoterol group. The rate ratio of Symbicort vs. Formoteroal was assessed by a negative binomial model.; Exacerbations, that met the modified Anthonisen criteria and duration =2 days were classified as moderate and severe exacerbations.; Moderate exacerbation: treatment of symptoms with systemic corticosteroids (=3 days) and/or antibiotics.; Severe exacerbation: symptoms that require hospitalization (including >24 hours in ED/urgent care setting).	Randomization at Week 0 to End of Treatment (EoT) W 26
Secondary	Number of Patients With Moderate or Severe COPD Exacerbation.	The number of patients who developed moderate or severe COPD exacerbation during treatment period were reported. Cox proportional hazards regression model was fitted to data to compare the two treatment arms .; The hazard ratio and 95% CI were estimated.	From randomzation to EoT W 26
Secondary	St. George's Respiratory Questionnaire (SGRQ)	SGRQ is a standardized, self-administered tool for measuring impaired health and perceived wellbeing in respiratory diseases; a validated electronic version of the questionnaire in the relevant validated languages was used in this study.; The questionnaire contains 50 items divided into three dimensions (Symptoms, Activity and Impact).; Each of the three dimensions of the questionnaire is scored separately in the range from 0 to 100: zero (0) score indicating no impairment of quality of life.; The total SGRQ score ranging from 0 to 100 is a summary score utilizing responses to all items calculated using weights attached to each item of the questionnaire.; Higher scores indicate poorer health and change of 4 units in the SGRQ has been determined to be the threshold for a clinically relevant change in health status.; The change from baseline was statistically summarized and compared between two arms in a mixed model.	From Run-in W -4 to EoT W 26
Secondary	Pre-dose/Pre-bronchodilator FEV1 at the Study Site	FEV1 from pre-dose spirometry is a measurement of lung function. The change from baseline on pre-dose FEV1 was summarized and compared between Symbicort and Formoterol groups using a mixed model.	From Run-in W -4 to EoT W 26
Secondary	Total Rescue Medication Use (Average Puffs/Day)	Use of rescue medication is a measure of symptoms that need to be treated with a short-acting bronchodilator.; The average daily use across the observation period was used for analysis. Change from baseline was summarized and compared between two arms using a mixed model.	From Run-in W -4 to EoT W 26
Secondary	Nights With Awakening Due to COPD	Nighttime awakening due to COPD symptoms correspond to the severity of nocturnal symptoms from COPD.; The average number of awakening per night over the treatment period was analyzed. It was derived as the number of night with awakening divided by the total number of nights with data in the recording period. Change from baseline period on awakening was summarized and compared between two arms using a mixed model.	From Run-in W -4 to EoT W 26

External Links

•   Symbicort RISE Revised CSP 3 4 FINAL Redacted