NCT02149199

Brief 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'.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
3,850

participants targeted

Target at P75+ for phase_3 asthma

Timeline
Completed

Started Jul 2014

Longer than P75 for phase_3 asthma

Geographic Reach
18 countries

255 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 16, 2014

Completed
13 days until next milestone

First Posted

Study publicly available on registry

May 29, 2014

Completed
1 month until next milestone

Study Start

First participant enrolled

July 7, 2014

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 2, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 2, 2017

Completed
2.1 years until next milestone

Results Posted

Study results publicly available

September 13, 2019

Completed
Last Updated

November 15, 2019

Status Verified

November 1, 2019

Enrollment Period

3.1 years

First QC Date

May 16, 2014

Results QC Date

August 2, 2018

Last Update Submit

November 4, 2019

Conditions

Outcome Measures

Primary Outcomes (1)

  • '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 Outcomes (19)

  • Number of Participants Experiencing at Least One Severe Asthma Exacerbation

    Day 1 up to 52 weeks

  • Number of Participants Experiencing at Least One Moderate or Severe Asthma Exacerbation

    Day 1 up to 52 weeks

  • Average Change From Baseline in Pre-dose Forced Expiratory Volume in 1 Second (FEV1)

    Study weeks 0,4,16,28,40,52

  • Average Change From Baseline in Morning Peak Expiratory Flow (PEF)

    up to 52 weeks

  • Average Change From Baseline in Evening PEF

    up to 52 weeks

  • +14 more secondary outcomes

Study Arms (3)

Symbicort "as needed"+placebo Pulmicort bid

EXPERIMENTAL

Symbicort (budesonide/formoterol) Turbuhaler 160/4.5 μg 'as needed' + Placebo Pulmicort Turbuhaler 200 μg bid

Drug: budesonide/formoterol 'as needed' + budesonide placebo bid

terbutaline "as needed"+placebo Pulmicort bid

ACTIVE COMPARATOR

terbutaline Turbuhaler 0.4 mg 'as needed' + placebo Pulmicort 200 μg Turbuhaler bid

Drug: terbutaline 'as needed' + placebo budesonide bid

Pulmicort bid + terbutaline "as needed"

ACTIVE COMPARATOR

Pulmicort 200 μg Turbuhaler bid + terbutaline 0.4 mg Turbuhaler 'as needed'

Drug: budesonide bid + terbutaline 'as needed'

Interventions

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

Symbicort "as needed"+placebo Pulmicort 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

terbutaline "as needed"+placebo Pulmicort bid

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

Pulmicort bid + terbutaline "as needed"

Eligibility Criteria

Age12 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (255)

Research Site

Bedford Park, 5042, Australia

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Concord, 2139, Australia

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Maroubra, 2035, Australia

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Murdoch, 6150, Australia

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Wollongong, 2522, Australia

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Alphaville, 06454-010, Brazil

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Botucatu, 18618-970, Brazil

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Porto Alegre, 90020-060, Brazil

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Porto Alegre, 90470-340, Brazil

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Porto Alegre, 90610-000, Brazil

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Salvador, 41940-455, Brazil

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Santo André, 09080-110, Brazil

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São Paulo, 04020-060, Brazil

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São Paulo, 04101-000, Brazil

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Sorocaba, 18040-425, Brazil

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Dupnitsa, 2600, Bulgaria

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Gotse Delchev, 2900, Bulgaria

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Kozloduy, 3320, Bulgaria

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Pazardzhik, 4400, Bulgaria

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Plovdiv, 4002, Bulgaria

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Razgrad, 7200, Bulgaria

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Roman, 3130, Bulgaria

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Rousse, 7002, Bulgaria

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Sandanski, 2800, Bulgaria

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Sofia, 1000, Bulgaria

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Sofia, 1152, Bulgaria

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Sofia, 1431, Bulgaria

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Sofia, 1606, Bulgaria

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Sofia, 1618, Bulgaria

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Varna, 9000, Bulgaria

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Velingrad, 4600, Bulgaria

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Vratsa, 3000, Bulgaria

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Edmonton, Alberta, T5A 4L8, Canada

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Sherwood Park, Alberta, T8L 0N2, Canada

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Maple Ridge, British Columbia, V2X 2L5, Canada

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North Vancouver, British Columbia, V7M 2H9, Canada

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Vancouver, British Columbia, V5Z 1M9, Canada

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Mount Pearl, Newfoundland and Labrador, A1N 1W7, Canada

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St. John's, Newfoundland and Labrador, A1A 3R5, Canada

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Ajax, Ontario, L1S 2J5, Canada

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Burlington, Ontario, L7N 3V2, Canada

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Cornwall, Ontario, K6H 4M4, Canada

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Etobicoke, Ontario, M9W 4L6, Canada

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Hamilton, Ontario, L8N 4A6, Canada

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Kanata, Ontario, K2L 3C8, Canada

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London, Ontario, N6H 0G6, Canada

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Mississauga, Ontario, L5A 3V4, Canada

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Newmarket, Ontario, L3Y 5G8, Canada

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North York, Ontario, M3M 3E5, Canada

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Ottawa, Ontario, K2H 8T5, Canada

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Sarnia, Ontario, N7T 4X3, Canada

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Toronto, Ontario, M9C 4Z5, Canada

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Toronto, Ontario, M9V 4B4, Canada

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Windsor, Ontario, N8X 2G1, Canada

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Lévis, Quebec, G6W 0M5, Canada

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Montreal, Quebec, H1M 1B1, Canada

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Montreal, Quebec, H3G 1L5, Canada

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Montreal, Quebec, H4J 1C5, Canada

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Pointe-Claire, Quebec, H9R 4S3, Canada

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Québec, Quebec, G1G 3Y8, Canada

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Québec, Quebec, G1V 4W2, Canada

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Québec, Quebec, G1W 4R4, Canada

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Québec, Quebec, G2J 0C4, Canada

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Saint-Charles-Borromée, Quebec, J6E 2B4, Canada

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Trois-Rivières, Quebec, G8T 7A1, Canada

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Victoriaville, Quebec, G6P 6P6, Canada

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Quillota, 2260000, Chile

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Santiago, 404366, Chile

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Santiago, 7750495, Chile

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Santiago, 7980378, Chile

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Santiago, 8380453, Chile

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Talcahuano, 4270918, Chile

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Beijing, 100043, China

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Beijing, 100050, China

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Changsha, 430033, China

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Chengdu, 610041, China

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Chengdu, 610083, China

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Guangzhou, 510120, China

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Guangzhou, 510515, China

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Haikou, 570311, China

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Hohhot, 010017, China

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Nanchang, 330006, China

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Shanghai, 200000, China

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Shanghai, 200032, China

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Shanghai, 200040, China

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Shanghai, 200120, China

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Shanghai, 200240, China

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Shanghai, 200433, China

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Shenyang, 110015, China

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Wenzhou, 325027, China

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Wuhan, CN-430030, China

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Xi'an, 710004, China

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Xi'an, 710038, China

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Xiamen, 361004, China

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Xuzhou, 221006, China

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Balassagyarmat, 2660, Hungary

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Berettyóújfalu, 4100, Hungary

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Budapest, 1195, Hungary

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Budapest, 1204, Hungary

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Edelény, 3780, Hungary

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Hajdúnánás, 4080, Hungary

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Mátészalka, 4700, Hungary

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Miskolc, 3529, Hungary

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Monor, 2200, Hungary

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Nyírbátor, 4300, Hungary

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Nyíregyháza, 4420, Hungary

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Pécs, 7626, Hungary

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Pécs, 7635, Hungary

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Szeged, H-6722, Hungary

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D.F., 03020, Mexico

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Durango, 43080, Mexico

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México, 04530, Mexico

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México, 06700, Mexico

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México, 06720, Mexico

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Monterrey, 64461, Mexico

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Morelia, 58070, Mexico

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Villahermosa, 86035, Mexico

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Cusco, CUSCO 01, Peru

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Lima, 41, Peru

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Lima, L18, Peru

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Lima, L27, Peru

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Lima, LIMA 1, Peru

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Lima, LIMA 31, Peru

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Lima, LIMA 41, Peru

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Piura, Peru

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Surco, LIMA 33, Peru

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Lipa City, 4217, Philippines

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Manila, 1000, Philippines

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Manila, 1003, Philippines

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Pasig, 1000, Philippines

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Quezon City, 1101, Philippines

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Bialystok, 15-003, Poland

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Bialystok, 15-430, Poland

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Elblag, 82-300, Poland

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Grodzisk Mazowiecki, 05-825, Poland

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Grudziądz, 86-300, Poland

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Kielce, 25-734, Poland

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Krakow, 30-901, Poland

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Krakow, 31-011, Poland

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Krakow, 31-209, Poland

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Krakow, 31-455, Poland

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Lodz, 90-141, Poland

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Lodz, 90-203, Poland

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Lodz, 91-103, Poland

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Poznan, 60-685, Poland

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Poznan, 60-823, Poland

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Rzeszów, 35-051, Poland

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Rzeszów, 35-612, Poland

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Skierniewice, 96-100, Poland

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Strzelce Opolskie, 47-100, Poland

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Szczecin, 70-111, Poland

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Szczecin, 71-124, Poland

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Słupca, 62-400, Poland

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Tarnów, 33-100, Poland

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Trzebnica, 55-100, Poland

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Turek, 62-700, Poland

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Zabrze, 41-800, Poland

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Bragadiru, 077025, Romania

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Brasov, 500051, Romania

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Brasov, 500283, Romania

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Cluj-Napoca, 400371, Romania

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Constanța, 900002, Romania

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Piteşti, 110084, Romania

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Timișoara, 300310, Romania

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Chelyabinsk, 454021, Russia

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Gatchina, 188300, Russia

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Ivanovo, 153005, Russia

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Kazan', 420012, Russia

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Kemerovo, 650002, Russia

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Kemerovo, 650099, Russia

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Krasnoyarsk, 660022, Russia

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Moscow, 105077, Russia

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Moscow, 109240, Russia

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Moscow, 117630, Russia

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Moscow, 119992, Russia

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Moscow, 123995, Russia

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Moscow, 127018, Russia

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Moscow, 142160, Russia

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Nizhny Novgorod, 603126, Russia

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Novosibirsk, 630008, Russia

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Novosibirsk, 630084, Russia

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Penza, 440067, Russia

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Perm, 614056, Russia

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Perm, 6144090, Russia

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Petrozavodsk, 185019, Russia

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Pyatigorsk, 357538, Russia

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Ryazan, 390026, Russia

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Saint Petersburg, 193312, Russia

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Saint Petersburg, 194100, Russia

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Saint Petersburg, 194354, Russia

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Saint Petersburg, 196084, Russia

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Saint Petersburg, 196211, Russia

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Saint Petersburg, 196657, Russia

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Saint Petersburg, 197022, Russia

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Saratov, 410012, Russia

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Ulyanovsk, 432009, Russia

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Vladikavkaz, 362007, Russia

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Volgograd, 400001, Russia

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Volgograd, 400131, Russia

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Voronezh, 394066, Russia

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Yaroslavl, 150002, Russia

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Yaroslavl, 150003, Russia

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Yekaterinburg, 620039, Russia

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Yekaterinburg, 620109, Russia

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Yekaterinburg, 620219, Russia

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Boksburg North, 1460, South Africa

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Durban, 4001, South Africa

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Durban, 4037, South Africa

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Durban, 4170, South Africa

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Johannesburg, 1818, South Africa

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Johannesburg, 2001, South Africa

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KwaDukuza, 4450, South Africa

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Middelburg, 1055, South Africa

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Queenswood, South Africa

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Verulam, 4345, South Africa

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Bucheon-si, 14584, South Korea

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Cheongju-si, 28644, South Korea

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Cheongju-si, 362-804, South Korea

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Incheon, 21431, South Korea

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Seoul, 03181, South Korea

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Seoul, 03312, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Seoul, 06591, South Korea

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Seoul, 07985, South Korea

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Seoul, 110-744, South Korea

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Cherkasy, 18009, Ukraine

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Dnipropetrovsk, 49074, Ukraine

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Ivano-Frankivsk, 76012, Ukraine

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Kharkiv, 61002, Ukraine

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Kharkiv, 61035, Ukraine

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Kharkiv, 61039, Ukraine

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Kharkiv, 61058, Ukraine

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Kharkiv, 61075, Ukraine

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Kharkiv, 61093, Ukraine

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Kyiv, 03049, Ukraine

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Kyiv, 03680, Ukraine

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Kyiv, Ukraine

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Lutsk, 43000, Ukraine

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Lutsk, 43024, Ukraine

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Lviv, 79066, Ukraine

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Odesa, 65025, Ukraine

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Vinnytsia, 21018, Ukraine

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Zaporizhzhya, 69068, Ukraine

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Bath, BA3 2UH, United Kingdom

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Coventry, CV6 4DD, United Kingdom

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Mortimer Reading, RG7 3SQ, United Kingdom

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Royal Leamington Spa, CV32 4RA, United Kingdom

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Trowbridge, BA14 8QA, United Kingdom

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Haiphong, 180000, Vietnam

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Hanoi, 100000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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Ho Chi Minh City, Vietnam

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Hochiminh, Vietnam

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Đông Nãi, 810000, Vietnam

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Related Publications (5)

  • FitzGerald JM, O'Byrne PM, Bateman ED, Barnes PJ, Zheng J, Ivanov S, Lamarca R, Larsdotter U, Emerath U, Jansen G, Puu M, Alagappan VKT, Surmont F, Reddel HK. Safety of As-Needed Budesonide-Formoterol in Mild Asthma: Data from the Two Phase III SYGMA Studies. Drug Saf. 2021 Apr;44(4):467-478. doi: 10.1007/s40264-020-01041-z. Epub 2021 Feb 6.

  • O'Byrne PM, FitzGerald JM, Bateman ED, Barnes PJ, Zheng J, Gustafson P, Lamarca R, Puu M, Keen C, Alagappan VKT, Reddel HK. Effect of a single day of increased as-needed budesonide-formoterol use on short-term risk of severe exacerbations in patients with mild asthma: a post-hoc analysis of the SYGMA 1 study. Lancet Respir Med. 2021 Feb;9(2):149-158. doi: 10.1016/S2213-2600(20)30416-1. Epub 2020 Oct 1.

  • O'Byrne PM, FitzGerald JM, Bateman ED, Barnes PJ, Zhong N, Keen C, Jorup C, Lamarca R, Ivanov S, Reddel HK. Inhaled Combined Budesonide-Formoterol as Needed in Mild Asthma. N Engl J Med. 2018 May 17;378(20):1865-1876. doi: 10.1056/NEJMoa1715274.

  • O'Byrne PM, FitzGerald JM, Zhong N, Bateman E, Barnes PJ, Keen C, Almqvist G, Pemberton K, Jorup C, Ivanov S, Reddel HK. The SYGMA programme of phase 3 trials to evaluate the efficacy and safety of budesonide/formoterol given 'as needed' in mild asthma: study protocols for two randomised controlled trials. Trials. 2017 Jan 10;18(1):12. doi: 10.1186/s13063-016-1731-4.

  • Reddel HK, Busse WW, Pedersen S, Tan WC, Chen YZ, Jorup C, Lythgoe D, O'Byrne PM. Should recommendations about starting inhaled corticosteroid treatment for mild asthma be based on symptom frequency: a post-hoc efficacy analysis of the START study. Lancet. 2017 Jan 14;389(10065):157-166. doi: 10.1016/S0140-6736(16)31399-X. Epub 2016 Nov 30.

Related Links

MeSH Terms

Conditions

Asthma

Interventions

Budesonide

Condition Hierarchy (Ancestors)

Bronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesRespiratory HypersensitivityHypersensitivity, ImmediateHypersensitivityImmune System Diseases

Intervention Hierarchy (Ancestors)

PregnenedionesPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Results Point of Contact

Title
Stefan Ivanov
Organization
AstraZeneca AB

Study Officials

  • Paul M O'Byrne, MB, FRCP(C), FRSC

    McMaster University, Hamilton, Canada

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 16, 2014

First Posted

May 29, 2014

Study Start

July 7, 2014

Primary Completion

August 2, 2017

Study Completion

August 2, 2017

Last Updated

November 15, 2019

Results First Posted

September 13, 2019

Record last verified: 2019-11

Locations