A Clinical Study to Evaluate Symbicort Turbuhaler Used 'as Needed' in Adults and Adolescents With Asthma. (SYGMA1)

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.

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'.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: budesonide/formoterol 'as needed' + budesonide placebo bid; Drug: terbutaline 'as needed' + placebo budesonide bid; Drug: budesonide bid + terbutaline 'as needed'

Detailed 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'

• Study Type: Interventional
• Enrollment (Actual): 3850
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia, 5042
    • Research Site
  • Concord, Australia, 2139
    • Research Site
  • Maroubra, Australia, 2035
    • Research Site
  • Murdoch, Australia, 6150
    • Research Site
  • Wollongong, Australia, 2522
    • Research Site
• Brazil
  • Alphaville, Brazil, 06454-010
    • Research Site
  • Botucatu, Brazil, 18618-970
    • Research Site
  • Porto Alegre, Brazil, 90610-000
    • Research Site
  • Porto Alegre, Brazil, 90470-340
    • Research Site
  • Porto Alegre, Brazil, 90020-060
    • Research Site
  • Salvador, Brazil, 41940-455
    • Research Site
  • Santo Andre, Brazil, 09080-110
    • Research Site
  • Sao Paulo, Brazil, 04020-060
    • Research Site
  • Sao Paulo, Brazil, 04101-000
    • Research Site
  • Sorocaba, Brazil, 18040-425
    • Research Site
• Bulgaria
  • Dupnitsa, Bulgaria, 2600
    • Research Site
  • Gotse Delchev, Bulgaria, 2900
    • Research Site
  • Kozloduy, Bulgaria, 3320
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  • Pazardzhik, Bulgaria, 4400
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  • Plovdiv, Bulgaria, 4002
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  • Razgrad, Bulgaria, 7200
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  • Roman, Bulgaria, 3130
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  • Ruse, Bulgaria, 7002
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  • Sandanski, Bulgaria, 2800
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  • Sofia, Bulgaria, 1000
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  • Sofia, Bulgaria, 1431
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  • Sofia, Bulgaria, 1606
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  • Sofia, Bulgaria, 1618
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  • Sofia, Bulgaria, 1152
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  • Varna, Bulgaria, 9000
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  • Velingrad, Bulgaria, 4600
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  • Vratsa, Bulgaria, 3000
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• Canada
  • Quebec, Canada, G1G 3Y8
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  • Quebec, Canada, G1W 4R4
    • Research Site
  • Quebec, Canada, G2J 0C4
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  • Alberta
    • Edmonton, Alberta, Canada, T5A 4L8
      • Research Site
    • Sherwood Park, Alberta, Canada, T8L 0N2
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  • British Columbia
    • Maple Ridge, British Columbia, Canada, V2X 2L5
      • Research Site
    • North Vancouver, British Columbia, Canada, V7M 2H9
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    • Vancouver, British Columbia, Canada, V5Z 1M9
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  • Newfoundland and Labrador
    • Mount Pearl, Newfoundland and Labrador, Canada, A1N 1W7
      • Research Site
    • St. John's, Newfoundland and Labrador, Canada, A1A 3R5
      • Research Site
  • Ontario
    • Ajax, Ontario, Canada, L1S 2J5
      • Research Site
    • Burlington, Ontario, Canada, L7N 3V2
      • Research Site
    • Cornwall, Ontario, Canada, K6H 4M4
      • Research Site
    • Etobicoke, Ontario, Canada, M9W 4L6
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    • Hamilton, Ontario, Canada, L8N 4A6
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    • Kanata, Ontario, Canada, K2L 3C8
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    • London, Ontario, Canada, N6H 0G6
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    • Mississauga, Ontario, Canada, L5A 3V4
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    • Newmarket, Ontario, Canada, L3Y 5G8
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    • North York, Ontario, Canada, M3M 3E5
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    • Ottawa, Ontario, Canada, K2H 8T5
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    • Sarnia, Ontario, Canada, N7T 4X3
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    • Toronto, Ontario, Canada, M9V 4B4
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    • Toronto, Ontario, Canada, M9C 4Z5
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    • Windsor, Ontario, Canada, N8X 2G1
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  • Quebec
    • Levis, Quebec, Canada, G6W 0M5
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    • Montreal, Quebec, Canada, H3G 1L5
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    • Montreal, Quebec, Canada, H4J 1C5
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    • Montreal, Quebec, Canada, H1M 1B1
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    • Pointe Claire, Quebec, Canada, H9R 4S3
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    • Quebec City, Quebec, Canada, G1V 4W2
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    • St Charles Borromee, Quebec, Canada, J6E 2B4
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    • Trois Rivieres, Quebec, Canada, G8T 7A1
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    • Victoriaville, Quebec, Canada, G6P 6P6
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• Chile
  • Quillota, Chile, 2260000
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  • Santiago, Chile, 8380453
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  • Santiago, Chile, 404366
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  • Santiago, Chile, 7750495
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  • Santiago, Chile, 7980378
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  • Talcahuano, Chile, 4270918
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• China
  • Beijing, China, 100050
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  • Beijing, China, 100043
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  • Changsha, China, 430033
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  • Chengdu, China, 610041
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  • Chengdu, China, 610083
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  • Guangzhou, China, 510120
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  • Guangzhou, China, 510515
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  • Haikou, China, 570311
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  • Hohhot, China, 010017
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  • Nanchang, China, 330006
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  • Shanghai, China, 200032
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  • Shanghai, China, 200433
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  • Shanghai, China, 200040
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  • Shanghai, China, 200120
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  • Shanghai, China, 200240
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  • Shanghai, China, 200000
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  • Shenyang, China, 110015
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  • Wenzhou, China, 325027
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  • Wuhan, China, CN-430030
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  • Xi'an, China, 710038
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  • Xi'an, China, 710004
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  • Xiamen, China, 361004
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  • Xuzhou, China, 221006
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• Hungary
  • Balassagyarmat, Hungary, 2660
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  • Berettyóújfalu, Hungary, 4100
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  • Budapest, Hungary, 1204
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  • Budapest, Hungary, 1195
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  • Edelény, Hungary, 3780
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  • Hajdúnánás, Hungary, 4080
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  • Miskolc, Hungary, 3529
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  • Monor, Hungary, 2200
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  • Mátészalka, Hungary, 4700
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  • Nyírbátor, Hungary, 4300
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  • Nyíregyháza, Hungary, 4420
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  • Pécs, Hungary, 7626
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  • Pécs, Hungary, 7635
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  • Szeged, Hungary, H-6722
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• Korea, Republic of
  • Bucheon-si, Korea, Republic of, 14584
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  • Cheongju-si, Korea, Republic of, 28644
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  • Cheongju-si, Korea, Republic of, 362-804
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  • Incheon, Korea, Republic of, 21431
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  • Seoul, Korea, Republic of, 03722
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  • Seoul, Korea, Republic of, 05505
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  • Seoul, Korea, Republic of, 03181
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  • Seoul, Korea, Republic of, 06591
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  • Seoul, Korea, Republic of, 03312
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  • Seoul, Korea, Republic of, 07985
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  • Seoul, Korea, Republic of, 110-744
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• Mexico
  • D.f., Mexico, 03020
    • Research Site
  • Durango, Mexico, 43080
    • Research Site
  • Mexico, Mexico, 06700
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  • Monterrey, Mexico, 64461
    • Research Site
  • Morelia, Mexico, 58070
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  • México, Mexico, 06720
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  • México, Mexico, 04530
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  • Villahermosa, Mexico, 86035
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• Peru
  • Cusco, Peru, CUSCO 01
    • Research Site
  • Lima, Peru, L27
    • Research Site
  • Lima, Peru, LIMA 41
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  • Lima, Peru, LIMA 1
    • Research Site
  • Lima, Peru, LIMA 31
    • Research Site
  • Lima, Peru, 41
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  • Lima, Peru, L18
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  • Piura, Peru
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  • Surco, Peru, LIMA 33
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• Philippines
  • Lipa City, Philippines, 4217
    • Research Site
  • Manila, Philippines, 1000
    • Research Site
  • Manila, Philippines, 1003
    • Research Site
  • Pasig City, Philippines, 1000
    • Research Site
  • Quezon City, Philippines, 1101
    • Research Site
• Poland
  • Białystok, Poland, 15-003
    • Research Site
  • Białystok, Poland, 15-430
    • Research Site
  • Elbląg, Poland, 82-300
    • Research Site
  • Grodzisk Mazowiecki, Poland, 05-825
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  • Grudziądz, Poland, 86-300
    • Research Site
  • Kielce, Poland, 25-734
    • Research Site
  • Kraków, Poland, 30-901
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  • Kraków, Poland, 31-011
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  • Kraków, Poland, 31-209
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  • Kraków, Poland, 31-455
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  • Poznań, Poland, 60-685
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  • Poznań, Poland, 60-823
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  • Rzeszów, Poland, 35-051
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  • Rzeszów, Poland, 35-612
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  • Skierniewice, Poland, 96-100
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  • Strzelce Opolskie, Poland, 47-100
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  • Szczecin, Poland, 70-111
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  • Szczecin, Poland, 71-124
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  • Słupca, Poland, 62-400
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  • Tarnów, Poland, 33-100
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  • Trzebnica, Poland, 55-100
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  • Turek, Poland, 62-700
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  • Zabrze, Poland, 41-800
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  • Łódź, Poland, 90-141
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  • Łódź, Poland, 91-103
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  • Łódź, Poland, 90-203
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• Romania
  • Bragadiru, Romania, 077025
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  • Brasov, Romania, 500283
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  • Brasov, Romania, 500051
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  • Cluj-Napoca, Romania, 400371
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  • Constanta, Romania, 900002
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  • Pitesti, Romania, 110084
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  • Timisoara, Romania, 300310
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• Russian Federation
  • Chelyabinsk, Russian Federation, 454021
    • Research Site
  • Ekaterinburg, Russian Federation, 620039
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  • Ekaterinburg, Russian Federation, 620109
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  • Ekaterinburg, Russian Federation, 620219
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  • Gatchina, Russian Federation, 188300
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  • Ivanovo, Russian Federation, 153005
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  • Kazan, Russian Federation, 420012
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  • Kemerovo, Russian Federation, 650002
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  • Kemerovo, Russian Federation, 650099
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  • Krasnoyarsk, Russian Federation, 660022
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  • Moscow, Russian Federation, 123995
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  • Moscow, Russian Federation, 119992
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  • Moscow, Russian Federation, 127018
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  • Moscow, Russian Federation, 109240
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  • Moscow, Russian Federation, 105077
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  • Moscow, Russian Federation, 117630
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  • Moscow, Russian Federation, 142160
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  • Nizhny Novgorod, Russian Federation, 603126
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  • Novosibirsk, Russian Federation, 630008
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  • Novosibirsk, Russian Federation, 630084
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  • Penza, Russian Federation, 440067
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  • Perm, Russian Federation, 6144090
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  • Perm, Russian Federation, 614056
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  • Petrozavodsk, Russian Federation, 185019
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  • Pyatigorsk, Russian Federation, 357538
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  • Ryazan, Russian Federation, 390026
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  • Saint - Petersburg, Russian Federation, 196211
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  • Saint - Petersburg, Russian Federation, 196657
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  • Saint Petersburg, Russian Federation, 193312
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  • Saint Petersburg, Russian Federation, 194100
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  • Saint Petersburg, Russian Federation, 196084
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  • Saint-Petersburg, Russian Federation, 196084
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  • Saint-Petersburg, Russian Federation, 197022
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  • Saratov, Russian Federation, 410012
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  • St. Petersburg, Russian Federation, 197022
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  • St.Petersburg, Russian Federation, 194354
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  • Ulyanovsk, Russian Federation, 432009
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  • Vladikavkaz, Russian Federation, 362007
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  • Volgograd, Russian Federation, 400001
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  • Volgograd, Russian Federation, 400131
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  • Voronezh, Russian Federation, 394066
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  • Yaroslavl, Russian Federation, 150003
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  • Yaroslavl, Russian Federation, 150002
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• South Africa
  • Boksburg North, South Africa, 1460
    • Research Site
  • Durban, South Africa, 4001
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  • Durban, South Africa, 4037
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  • Durban, South Africa, 4170
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  • Johannesburg, South Africa, 1818
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  • Johannesburg, South Africa, 2001
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  • Middelburg, South Africa, 1055
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  • Queenswood, South Africa
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  • Stanger, South Africa, 4450
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  • Verulam, South Africa, 4345
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• Ukraine
  • Cherkasy, Ukraine, 18009
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  • Dnipropetrovsk, Ukraine, 49074
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  • Ivano-Frankivsk, Ukraine, 76012
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  • Kharkiv, Ukraine, 61002
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  • Kharkiv, Ukraine, 61039
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  • Kharkiv, Ukraine, 61058
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  • Kharkiv, Ukraine, 61075
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  • Kharkiv, Ukraine, 61035
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  • Kharkiv, Ukraine, 61093
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  • Kyiv, Ukraine
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  • Kyiv, Ukraine, 03049
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  • Kyiv, Ukraine, 03680
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  • Lutsk, Ukraine, 43000
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  • Lutsk, Ukraine, 43024
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  • Lviv, Ukraine, 79066
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  • Odesa, Ukraine, 65025
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  • Vinnytsia, Ukraine, 21018
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  • Zaporizhzhya, Ukraine, 69068
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• United Kingdom
  • Bath, United Kingdom, BA3 2UH
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  • Coventry, United Kingdom, CV6 4DD
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  • Leamington Spa, United Kingdom, CV32 4RA
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  • Mortimer Reading, United Kingdom, RG7 3SQ
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  • Trowbridge, United Kingdom, BA14 8QA
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• Vietnam
  • Dong Nai, Vietnam, 810000
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  • Hai Phong, Vietnam, 180000
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  • Hanoi, Vietnam, 100000
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  • Ho Chi Minh, Vietnam
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  • Ho Chi Minh, Vietnam, 700000
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  • Hochiminh, Vietnam
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Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 130 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Symbicort "as needed"+placebo Pulmicort bid; Symbicort (budesonide/formoterol) Turbuhaler 160/4.5 μg 'as needed' + Placebo Pulmicort Turbuhaler 200 μg bid	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
Active Comparator: Pulmicort bid + terbutaline "as needed"; Pulmicort 200 μg Turbuhaler bid + terbutaline 0.4 mg Turbuhaler 'as needed'	Drug: 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
Active Comparator: terbutaline "as needed"+placebo Pulmicort bid; terbutaline Turbuhaler 0.4 mg 'as needed' + placebo Pulmicort 200 μg Turbuhaler bid	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
'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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
Number of Patients With Study Specific Asthma Related Discontinuation	Study specific asthma related discontinuation	up to 52 weeks
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
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
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
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
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
Annual Severe Asthma Exacerbation Rate	Severe asthma exacerbations over the randomised treatment period.	up to 52 weeks
Annual Moderate or Severe Asthma Exacerbation Rate	Moderate or severe asthma exacerbations during the randomised treatment period.	up to 52 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Paul M O'Byrne, MB, FRCP(C), FRSC, McMaster University, Hamilton, Canada

Publications and helpful links

General Publications

• 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, 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.
• 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.

Helpful Links

• D589SC00001-statistical-analysis-plan-edition-4_29Sep2017_pdfa

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2014
• Primary Completion (Actual): August 2, 2017
• Study Completion (Actual): August 2, 2017

Study Registration Dates

• First Submitted: May 16, 2014
• First Submitted That Met QC Criteria: May 26, 2014
• First Posted (Estimate): May 29, 2014

Study Record Updates

• Last Update Posted (Actual): November 15, 2019
• Last Update Submitted That Met QC Criteria: November 4, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Sympathomimetics; Budesonide; Formoterol Fumarate; Terbutaline
• Other Study ID Numbers: D589SC00001; 2013-004474-96 (EudraCT Number)