A Clinical Study to Evaluate Symbicort Turbuhaler Used 'as Needed' in Adults and Adolescents With Asthma.

Asthma Clinical Trial

— SYGMA1  

Official title:

A Clinical Study Comparing Symbicort® 'as Needed' With Terbutaline 'as Needed' and With Pulmicort® Twice Daily Plus Terbutaline 'as Needed' in Adult and Adolescent Patients With Asthma.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02149199
• Other study ID #: D589SC00001
• Secondary ID: 2013-004474-96
• Status: Completed
• Phase: Phase 3
• Start date: July 7, 2014
• Est. completion date: August 2, 2017

Study information

• Verified date: November 2019
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test if Symbicort® (budesonide/formoterol) Turbuhaler® is effective in treating asthma when used 'as needed' in patients with milder asthma. The efficacy of Symbicort® 'as needed' will be compared with: 1) terbutaline Turbuhaler® 'as needed' and with 2) Pulmicort (budesonide) Turbuhaler® twice daily plus terbutaline Turbuhaler® 'as needed'.

Description:

A 52-week, double-blind, randomised, multi-centre, parallel-group, Phase III study in patients 12 years and older with asthma, evaluating the efficacy and safety of Symbicort® (budesonide/formoterol) Turbuhaler® 160/4.5 μg 'as needed' compared with terbutaline Turbuhaler® 0.4 mg 'as needed' and with Pulmicort® (budesonide) Turbuhaler® 200 μg twice daily plus terbutaline Turbuhaler® 0.4 mg 'as needed'

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3850
• Est. completion date: August 2, 2017
• Est. primary completion date: August 2, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 130 Years

Eligibility

INCLUSION CRITERIA 1. Provision of informed consent prior to any study specific procedures. For patients under-age, signed informed consent from both the patient and the patient's parent/legal guardian is required 2. Male or Female, =12 years of age 3. Documented diagnosis of asthma for at least 6 months prior to Visit 1 4. Patients who are in need of Step 2 treatment according to Global Initiative for Asthma guidelines 5. Patients treated with 'as needed' inhaled short-acting bronchodilator(s) only should have pre-bronchodilator Forced Expiratory Volume in one second (FEV1) = 60 % of Predicted Normal (PN) and post-bronchodilator FEV1 = 80 % PN 6. Patients treated with low stable dose of inhaled corticosteroid or leukotriene antagonist in addition to 'as needed' use of inhaled short-acting bronchodilator(s) should have pre-bronchodilator FEV1 =80 % PN 7. Patients should have reversible airway obstruction 8. To be randomized patients must have used Bricanyl Turbuhaler 'as needed' on at least 3 separate days during the last week of the run in period. EXCLUSION CRITERIA 1. Patient has a history of life-threatening asthma including intubation and intensive care unit admission 2. Patient has had an asthma worsening requiring change in treatment other than inhaled short-acting bronchodilator(s) within 30 days prior to Visit 1 or between Visits 1 and 2; or a treatment other than Bricanyl Turbuhaler from Visit 2 until randomization 3. Patient has required treatment with oral, rectal or parenteral glucocorticosteroids (GCS) within 30 days and/or depot parenteral GCS within 12 weeks prior to Visit 1 4. Smoker (current or previous) with a smoking history of = 10 pack years 5. Pregnancy, breast-feeding or planned pregnancy during the study.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• budesonide/formoterol 'as needed' + budesonide placebo bid
Symbicort (budesonide/ formoterol) 160/4.5 µg powder for inhalation 'as needed' plus Pulmicort placebo 200 µg powder for inhalation, 1 inhalation twice daily (morning and evening), 52-week treatment
• terbutaline 'as needed' + placebo budesonide bid
Terbutaline 0.4 mg powder for inhalation 'as needed' plus placebo Pulmicort (budesonide) 200 µg powder for inhalation, 1 inhalation twice daily (morning and evening), 52-week treatment
• budesonide bid + terbutaline 'as needed'
Pulmicort (budesonide) 200 µg powder for inhalation, 1 inhalation twice daily (morning and evening) plus terbutaline 0.4 mg powder for inhalation 'as needed', 52-week treatment

Locations

Country	Name	City	State
Australia	Research Site	Bedford Park
Australia	Research Site	Concord
Australia	Research Site	Maroubra
Australia	Research Site	Murdoch
Australia	Research Site	Wollongong
Brazil	Research Site	Alphaville
Brazil	Research Site	Botucatu
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Salvador
Brazil	Research Site	Santo Andre
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sorocaba
Bulgaria	Research Site	Dupnitsa
Bulgaria	Research Site	Gotse Delchev
Bulgaria	Research Site	Kozloduy
Bulgaria	Research Site	Pazardzhik
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Razgrad
Bulgaria	Research Site	Roman
Bulgaria	Research Site	Ruse
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	Varna
Bulgaria	Research Site	Velingrad
Bulgaria	Research Site	Vratsa
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Cornwall	Ontario
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Etobicoke	Ontario
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Kanata	Ontario
Canada	Research Site	Levis	Quebec
Canada	Research Site	London	Ontario
Canada	Research Site	Maple Ridge	British Columbia
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Mount Pearl	Newfoundland and Labrador
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	North Vancouver	British Columbia
Canada	Research Site	North York	Ontario
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Pointe Claire	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec City	Quebec
Canada	Research Site	Sarnia	Ontario
Canada	Research Site	Sherwood Park	Alberta
Canada	Research Site	St Charles Borromee	Quebec
Canada	Research Site	St. John's	Newfoundland and Labrador
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Trois Rivieres	Quebec
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Victoriaville	Quebec
Canada	Research Site	Windsor	Ontario
Chile	Research Site	Quillota
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Talcahuano
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Haikou
China	Research Site	Hohhot
China	Research Site	Nanchang
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Wenzhou
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Xi'an
China	Research Site	Xiamen
China	Research Site	Xuzhou
Hungary	Research Site	Balassagyarmat
Hungary	Research Site	Berettyóújfalu
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Edelény
Hungary	Research Site	Hajdúnánás
Hungary	Research Site	Mátészalka
Hungary	Research Site	Miskolc
Hungary	Research Site	Monor
Hungary	Research Site	Nyírbátor
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Pécs
Hungary	Research Site	Pécs
Hungary	Research Site	Szeged
Korea, Republic of	Research Site	Bucheon-si
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	D.f.
Mexico	Research Site	Durango
Mexico	Research Site	Mexico
Mexico	Research Site	México
Mexico	Research Site	México
Mexico	Research Site	Monterrey
Mexico	Research Site	Morelia
Mexico	Research Site	Villahermosa
Peru	Research Site	Cusco
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Piura
Peru	Research Site	Surco
Philippines	Research Site	Lipa City
Philippines	Research Site	Manila
Philippines	Research Site	Manila
Philippines	Research Site	Pasig City
Philippines	Research Site	Quezon City
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Elblag
Poland	Research Site	Grodzisk Mazowiecki
Poland	Research Site	Grudziadz
Poland	Research Site	Kielce
Poland	Research Site	Kraków
Poland	Research Site	Kraków
Poland	Research Site	Kraków
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Lódz
Poland	Research Site	Lódz
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Rzeszów
Poland	Research Site	Rzeszów
Poland	Research Site	Skierniewice
Poland	Research Site	Slupca
Poland	Research Site	Strzelce Opolskie
Poland	Research Site	Szczecin
Poland	Research Site	Szczecin
Poland	Research Site	Tarnów
Poland	Research Site	Trzebnica
Poland	Research Site	Turek
Poland	Research Site	Zabrze
Romania	Research Site	Bragadiru
Romania	Research Site	Brasov
Romania	Research Site	Brasov
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Constanta
Romania	Research Site	Pitesti
Romania	Research Site	Timisoara
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Gatchina
Russian Federation	Research Site	Ivanovo
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Krasnoyarsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Nizhny Novgorod
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Petrozavodsk
Russian Federation	Research Site	Pyatigorsk
Russian Federation	Research Site	Ryazan
Russian Federation	Research Site	Saint - Petersburg
Russian Federation	Research Site	Saint - Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St.Petersburg
Russian Federation	Research Site	Ulyanovsk
Russian Federation	Research Site	Vladikavkaz
Russian Federation	Research Site	Volgograd
Russian Federation	Research Site	Volgograd
Russian Federation	Research Site	Voronezh
Russian Federation	Research Site	Yaroslavl
Russian Federation	Research Site	Yaroslavl
South Africa	Research Site	Boksburg North
South Africa	Research Site	Durban
South Africa	Research Site	Durban
South Africa	Research Site	Durban
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Middelburg
South Africa	Research Site	Queenswood
South Africa	Research Site	Stanger
South Africa	Research Site	Verulam
Ukraine	Research Site	Cherkasy
Ukraine	Research Site	Dnipropetrovsk
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lutsk
Ukraine	Research Site	Lutsk
Ukraine	Research Site	Lviv
Ukraine	Research Site	Odesa
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zaporizhzhya
United Kingdom	Research Site	Bath
United Kingdom	Research Site	Coventry
United Kingdom	Research Site	Leamington Spa
United Kingdom	Research Site	Mortimer Reading
United Kingdom	Research Site	Trowbridge
Vietnam	Research Site	Dong Nai
Vietnam	Research Site	Hai Phong
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Hochiminh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Australia,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Hungary,  Korea, Republic of,  Mexico,  Peru,  Philippines,  Poland,  Romania,  Russian Federation,  South Africa,  Ukraine,  United Kingdom,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	'Well-controlled Asthma Week' - a Derived Binary Variable (Yes/No)	A well-controlled asthma week is defined as the fulfilment of both conditions A) and B) below: A) Two or more of the following criteria are fulfilled: - No more than 2 days with a daily asthma symptom score >1 - No more than 2 days of 'as needed' medication use, up to a maximum of 4 occasions per week (multiple occasions per day should be regarded as separate occasions) - Morning PEF =80% of Predicted Normal every day B) Both of the following criteria are fulfilled: - No nighttime awakenings due to asthma - No additional inhaled and/or systemic glucocorticosteroid treatment due to asthma. The binary variable well-controlled asthma week was derived for each patient and study week. In addition, for each week, the percent of patients with well-controlled asthma week was derived. It is required that the eDiary had to be completed on at least 5 days in a week to be a well-controlled asthma week.	Weekly, up to 52 weeks
Secondary	Number of Participants Experiencing at Least One Severe Asthma Exacerbation	A severe exacerbation is defined as a deterioration of asthma requiring any of the following: use of systemic glucocorticosteroids (GCS) for at least 3 days, inpatient hospitalization, or emergency room visit due to asthma that required systemic steroids	Day 1 up to 52 weeks
Secondary	Number of Participants Experiencing at Least One Moderate or Severe Asthma Exacerbation	A moderate exacerbation is defined as a deterioration of asthma requiring a change in treatment, i.e. initiation of prescribed additional ICS treatment to avoid progression of the worsening of asthma to a severe exacerbation.; A severe exacerbation is defined as a deterioration of asthma requiring any of the following: use of systemic glucocorticosteroids (GCS) for at least 3 days, inpatient hospitalization, or emergency room visit due to asthma that required systemic steroids	Day 1 up to 52 weeks
Secondary	Average Change From Baseline in Pre-dose Forced Expiratory Volume in 1 Second (FEV1)	Overall estimate of FEV1 (mL) pre-bronchodilator change from baseline. Baseline is the measurement at Visit 3 (prior to first dose of Investigational Product) from MMRM (mixed model repeated measures analysis).	Study weeks 0,4,16,28,40,52
Secondary	Average Change From Baseline in Morning Peak Expiratory Flow (PEF)	Morning peak expiratory flow (eDiary) change from baseline over the randomised treatment period. Baseline is defined as the mean of all non-missing morning measurements during the last 10 days of the run-in period.	up to 52 weeks
Secondary	Average Change From Baseline in Evening PEF	Evening peak expiratory flow (eDiary) change from baseline during the randomised treatment period. Baseline is defined as the mean of all non-missing evening measurements during the last 10 days of the run-in period.	up to 52 weeks
Secondary	Average Change From Baseline in Number of Inhalations of 'as Needed' Medication.	'As needed' inhalations change from baseline over the randomised treatment period. Baseline is defined as the last 10 days of the run-in period. 'As needed' use was calculated as the cumulative doses of 'as needed' medication over the randomised treatment period divided by the follow-up time (number of days - 1). ie, average number of inhalations per day.	up to 52 weeks
Secondary	Average Change From Baseline in Asthma Symptom Score	Asthma symptom score (eDiary) change from baseline during the randomised treatment period. Symptom score is entered morning and evening by the patient on a 4-point scale from 0 to 3 with higher values indicating more severe symptoms. Asthma symptom score is then the sum of the day and night scores, which implies a range of scores from 0 - 6, with higher values indicating more severe symptoms. Baseline is defined as the mean of all non-missing measurements during the last 10 days of the run-in period.	up to 52 weeks
Secondary	Change From Baseline in the Percentage of Nighttime Awakenings Due to Asthma	Night-time awakenings (%) due to asthma change from baseline. Variable analysed is the proportion (%) of nights during the relevant period with night-time awakenings. Baseline refers to the last 10 nights of the run-in period.	up to 52 weeks
Secondary	Change From Baseline in Percentage of Symptom-free Days	Symptom-free days (%) change from baseline during the randomised treatment period.Variable analysed is the proportion (%) of symptom-free days during the relevant period. Baseline refers to the last 10 days of the run-in period.	up to 52 weeks
Secondary	Change From Baseline in Percentage of 'As Needed' Free Days	'As needed' free days (%) change from baseline during the randomised treatment period. An 'as needed' free day is defined as a day and night with no use of 'as needed' medication. Variable analysed is the proportion (%) of 'as needed' free days during the relevant period. Baseline refers to the last 10 days of the run-in period.	up to 52 weeks
Secondary	Change From Baseline in Percentage of Asthma Control Days	Asthma control days (%) change from baseline. An asthma control day is defined as the fulfilment of all of the following criteria; a day and night with no asthma symptoms, a night with no awakenings due to asthma symptoms and a day and night with no use of 'as needed' medication. Variable analysed is the proportion (%) of asthma control days during the randomised treatment period. Baseline refers to the last 10 days of the run-in period.	up to 52 weeks
Secondary	Number of Patients With Study Specific Asthma Related Discontinuation	Study specific asthma related discontinuation	up to 52 weeks
Secondary	Poorly Controlled Asthma Weeks	A poorly-controlled asthma week is defined as a week meeting any one of the following conditions: Two or more consecutive days with awakenings due to asthma on both nights; A recorded use of 'as needed' medication for symptom relief of at least 3 occasions per day, for at least 2 consecutive days; Additional systemic GCS treatment required for severe exacerbation. If there were sufficient data within a week available to confirm the week was not poorly-controlled, the week is labelled as 'does not meet criteria for poorly-controlled'.	Weekly for up to 52 weeks
Secondary	Number of Participants Experiencing at Least One Occasion With Additional Steroids for Asthma	Additional steroids for asthma includes any additional inhaled and/or systemic glucocorticosteroids treatment due to asthma while in the randomised treatment period.	Day 1 up to 52 weeks
Secondary	Average Change From Baseline in Asthma Control Questionnaire (ACQ-5)	Asthma Control Questionnaire 5-item version score change from baseline. ACQ questionnaire contains five questions on patients' symptoms, which are assessed on a 7-point scale from 0 (representing good control) to 6 (representing poor control). The score is the mean score of all questions for which responses are provided.	Study weeks 0,4,16,28,40,52
Secondary	Average Change From Baseline in Asthma Quality of Life Questionnaire; Standard Version (AQLQ(S))	Asthma Quality of Life Questionnaire Standardised Version (AQLQ (S) overall score change from baseline. AQLQ(S) consists of 32 questions in 4 domains. Each question is assessed on a 7-point scale from 1 to 7, with higher values indicating better health-related quality of life. The overall score is calculated as the mean score of all 32 items.	Study weeks 0,16,28,40,52
Secondary	Percentage of Controller Use Days	ICS controller use days (%) during the randomised treatment period is calculated as the cumulative number of days when any controller medication (containing ICS) was taken including maintenance (Pulmicort bid group) and 'as needed' medication (Symbicort 'as needed' group) and additional prescribed ICS for asthma exacerbations and/or long term poor asthma control (all treatment groups), divided by the number of days in the randomised treatment period.	up to 52 weeks
Secondary	Annual Severe Asthma Exacerbation Rate	Severe asthma exacerbations over the randomised treatment period.	up to 52 weeks
Secondary	Annual Moderate or Severe Asthma Exacerbation Rate	Moderate or severe asthma exacerbations during the randomised treatment period.	up to 52 weeks

External Links

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