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

Asthma Clinical Trial

— SYGMA2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02224157
• Other study ID #: D589SC00003
• Secondary ID: 2013-004473-28
• Status: Completed
• Phase: Phase 3
• Start date: November 28, 2014
• Est. completion date: August 16, 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 Pulmicort (budesonide) Turbuhaler twice daily plus terbutaline Turbuhaler 'as needed'

Description:

A 52-week, double-blind, randomised, multi-centre, phase III, parallel-group 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 Pulmicort (budesonide) Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg 'as needed'

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4215
• Est. completion date: August 16, 2017
• Est. primary completion date: August 16, 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 GINA step 2 treatment

5. Patients treated with a short acting inhaled bronchodilator(s) only should have pre-bronchodilator FEV1 = 60 % of predicted normal (PN) and post-bronchodilator FEV1 = 80 % PN

6. Patients treated with low stable dose of ICS or leukotriene antagonists in addition to short acting inhaled 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 short acting inhaled bronchodilator(s) within 30 days prior to Visit 1 and from Visit 1 until randomization

3. Patient has required treatment with oral, rectal or parenteral GCS within 30 days and/or depot parenteral GCS within 12 weeks prior to Visit 1

4. Current or previous smoker 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
• budesonode 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	Sydney
Brazil	Research Site	Botucatu
Brazil	Research Site	Florianopolis
Brazil	Research Site	Goiania
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
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	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Sorocaba
Bulgaria	Research Site	Blagoevgrad
Bulgaria	Research Site	Pernik
Bulgaria	Research Site	Petrich
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Razlog
Bulgaria	Research Site	Sliven
Bulgaria	Research Site	Smolyan
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
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	Varna
Bulgaria	Research Site	Veliko Tarnovo
Bulgaria	Research Site	Vidin
Bulgaria	Research Site	Yambol
Chile	Research Site	Curico
Chile	Research Site	Quillota
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Talca
Chile	Research Site	Viña del Mar
Colombia	Research Site	Barranquilla
Colombia	Research Site	Bogota
Colombia	Research Site	Bogotá
Colombia	Research Site	Bogotá
Colombia	Research Site	Medellin
Czechia	Research Site	Ceska Lipa
Czechia	Research Site	Kladno
Czechia	Research Site	Kralupy nad Vltavou
Czechia	Research Site	Kutna Hora
Czechia	Research Site	Liberec 1
Czechia	Research Site	Neratovice
Czechia	Research Site	Ostrava
Czechia	Research Site	Ostrava
Czechia	Research Site	Pardubice
Czechia	Research Site	Plzen
Czechia	Research Site	Plzen
Czechia	Research Site	Praha
Czechia	Research Site	Praha 4
Czechia	Research Site	Praha 5
Czechia	Research Site	Rokycany
Czechia	Research Site	Rudna U Prahy
Czechia	Research Site	Tabor
Czechia	Research Site	Teplice
Czechia	Research Site	Zatec
France	Research Site	Brii-sous-forges
France	Research Site	Colmar
France	Research Site	Joue-les-Tours
France	Research Site	Nantes Cedex 2
France	Research Site	Nimes
France	Research Site	Reze
Germany	Research Site	Bad Lippspringe
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Cottbus
Germany	Research Site	Frankfurt/Main
Germany	Research Site	Geesthacht
Germany	Research Site	Großhansdorf
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Leipzig
Germany	Research Site	Leipzig
Germany	Research Site	Leipzig
Germany	Research Site	Lübeck
Germany	Research Site	Neu-Isenburg
Germany	Research Site	Oldenburg
Germany	Research Site	Reinfeld
Germany	Research Site	Rüdersdorf
Germany	Research Site	Schleswig
Germany	Research Site	Warendorf
Hungary	Research Site	Aszód
Hungary	Research Site	Balassagyarmat
Hungary	Research Site	Berettyóújfalu
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Cegléd
Hungary	Research Site	Érd
Hungary	Research Site	Gödöllo
Hungary	Research Site	Gyula
Hungary	Research Site	Gyula
Hungary	Research Site	Hajdúnánás
Hungary	Research Site	Létavértes
Hungary	Research Site	Makó
Hungary	Research Site	Miskolc
Hungary	Research Site	Mórahalom
Hungary	Research Site	Pécs
Hungary	Research Site	Siófok
Hungary	Research Site	Szeged
Hungary	Research Site	Szombathely
Hungary	Research Site	Vásárosnamény
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seongnam-si
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
Korea, Republic of	Research Site	Suwon-si
Korea, Republic of	Research Site	Uijeongbu-si
Korea, Republic of	Research Site	Wonju-si
Mexico	Research Site	Chihuahua
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mérida
Mexico	Research Site	México
Mexico	Research Site	Mexico City
Mexico	Research Site	San Juan del Rio
Mexico	Research Site	Tlanepantla
Mexico	Research Site	Villahermosa
Mexico	Research Site	Zapopan
New Zealand	Research Site	Auckland
New Zealand	Research Site	Christchurch
New Zealand	Research Site	Christchurch
New Zealand	Research Site	Christchurch Central
New Zealand	Research Site	Grafton
New Zealand	Research Site	Hamilton West
New Zealand	Research Site	Maroubra
New Zealand	Research Site	New Lambton
New Zealand	Research Site	Newtown
New Zealand	Research Site	Rotorua
New Zealand	Research Site	South Brisbane
New Zealand	Research Site	Tauranga
New Zealand	Research Site	Wellington
Peru	Research Site	Cercado De Lima
Peru	Research Site	Chancay
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Miraflores
Peru	Research Site	Santa Beatriz
Philippines	Research Site	Lipa City
Philippines	Research Site	Manila
Philippines	Research Site	Pasig City
Philippines	Research Site	Quezon City
Philippines	Research Site	Quezon City
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Gizycko
Poland	Research Site	Koscian
Poland	Research Site	Kraków
Poland	Research Site	Lublin
Poland	Research Site	Mragowo
Poland	Research Site	Ostrów Wielkopolski
Poland	Research Site	Ostrowiec Swietokrzyski
Poland	Research Site	Pabianice
Poland	Research Site	Pila
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Proszowice
Poland	Research Site	Rzeszów
Poland	Research Site	Warszawa
Poland	Research Site	Zabrze
Romania	Research Site	Bragadiru
Romania	Research Site	Brasov
Romania	Research Site	Brasov
Romania	Research Site	Bucharest
Romania	Research Site	Constanta
Romania	Research Site	Constanta
Romania	Research Site	Deva
Romania	Research Site	Iasi
Romania	Research Site	Pitesti
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Gatchina
Russian Federation	Research Site	Ivanovo
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Kemerovo
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	Novosibirsk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Pskov
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	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	Saratov
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St.Petersburg
Russian Federation	Research Site	Tomsk
Russian Federation	Research Site	Tver
Russian Federation	Research Site	Ufa
Russian Federation	Research Site	Ulyanovsk
Russian Federation	Research Site	Vladikavkaz
Russian Federation	Research Site	Volgograd
Russian Federation	Research Site	Vsevolozhsk
Russian Federation	Research Site	Yaroslavl
Saudi Arabia	Research Site	Dhahran
Saudi Arabia	Research Site	Jeddah
Saudi Arabia	Research Site	Jeddah
Saudi Arabia	Research Site	Riyadh
Saudi Arabia	Research Site	Riyadh
Slovakia	Research Site	Kezmarok
Slovakia	Research Site	Komarno
Slovakia	Research Site	Kosice
Slovakia	Research Site	Kosice
Slovakia	Research Site	Levice
Slovakia	Research Site	Liptovsky Mikulas
Slovakia	Research Site	Lucenec
Slovakia	Research Site	Nitra
Slovakia	Research Site	Nove Zamky
Slovakia	Research Site	Poprad
Slovakia	Research Site	Poprad
Slovakia	Research Site	Rimavska Sobota
Slovakia	Research Site	Ruzomberok
Slovakia	Research Site	Skalica
Slovakia	Research Site	Surany
Slovakia	Research Site	Topolcany
Slovakia	Research Site	Trebisov
Slovakia	Research Site	Zilina
Slovakia	Research Site	Zvolen
South Africa	Research Site	Bellville
South Africa	Research Site	Boksburg North
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	Durban
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Lenasia
South Africa	Research Site	Mowbray
South Africa	Research Site	Panorama
South Africa	Research Site	Phoenix
South Africa	Research Site	Verulam
Spain	Research Site	Alicante
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Bilbao (Vizcaya)
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Marbella (Málaga)
Spain	Research Site	Oviedo
Spain	Research Site	Sevilla
Spain	Research Site	Sevilla
Spain	Research Site	Terrassa (Barcelona)
Spain	Research Site	Valencia
Sweden	Research Site	Borås
Sweden	Research Site	Lund
Sweden	Research Site	Malmo
Sweden	Research Site	Stockholm
Sweden	Research Site	Värnamo
Sweden	Research Site	Västra Frölunda
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Chonburi
Thailand	Research Site	Hat Yai
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Muang,
Thailand	Research Site	Nonthaburi
Thailand	Research Site	Pathumthani
Ukraine	Research Site	Cherkasy
Ukraine	Research Site	Chernihiv
Ukraine	Research Site	Chernivtsi
Ukraine	Research Site	Dnipro
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kherson
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lutsk
Ukraine	Research Site	Lviv
Ukraine	Research Site	Odesa
Ukraine	Research Site	Odessa
Ukraine	Research Site	Ternopil
Ukraine	Research Site	Uzhgorod
Ukraine	Research Site	Uzhgorod
Ukraine	Research Site	Uzhgorod
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zaporizhzhya
Ukraine	Research Site	Zaporizhzhya
Vietnam	Research Site	Can Tho
Vietnam	Research Site	Ha Noi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Hochiminh
Vietnam	Research Site	Hue

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Australia,  Brazil,  Bulgaria,  Chile,  Colombia,  Czechia,  France,  Germany,  Hungary,  Korea, Republic of,  Mexico,  New Zealand,  Peru,  Philippines,  Poland,  Romania,  Russian Federation,  Saudi Arabia,  Slovakia,  South Africa,  Spain,  Sweden,  Thailand,  Ukraine,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annual Severe Asthma Exacerbation Rate - Non-inferiority Analysis	Severe asthma exacerbations over the randomised treatment period, negative binomial model for non-inferiority test evaluation	up to 52 weeks
Primary	Annual Severe Asthma Exacerbation Rate - Superiority Analysis	Severe asthma exacerbations over the randomised treatment period, negative binomial model for superiority test evaluation	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	Average Change From Baseline in Pre-bronchodilator FEV1	The average change from baseline (baseline defined by measurement at week 0, prior to first dose of IP) to the treatment period average assessed over the entire treatment period in pre-bronchodilator FEV1 was derived by computing a contrast for the mean across the post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.	Study weeks 0,17, 34, 52
Secondary	Number of Participants With Study Specific Asthma Related Discontinuation	The following two criteria lead to discontinuation from the IP due to asthma related events: A severe asthma exacerbation with duration for more than 3 weeks, and/or three severe asthma exacerbations during 6 months.	Day 1 up to 52 weeks
Secondary	Average Change From Baseline in 'as Needed' Use	'As-needed' use change from baseline over the randomised treatment period. Baseline was 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.	Week 0 up to 52 weeks
Secondary	Change From Baseline in Percent of 'as Needed' Free Days	'As needed' free days (%) change from baseline during randomised treatment period. An 'as-needed' free day was defined as a day and night with no use of 'as needed' medication. Variable analysed is the percentage (%) of 'as-needed' free days during the randomised treatment period. Baseline is defined by the last 10 days of the run-in period.	Week 0 up to 52 weeks
Secondary	Percentage of Controller Use Days	ICS controller use days (%) during the randomised treatment period is calculated as the cumulative 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 (all treatment groups), divided by the number of days in the randomised treatment period.	Week 0 up to 52 weeks
Secondary	Average Change From Baseline in Asthma Control Questionnaire (5-item Version) - ACQ-5 Score	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. The average change from baseline to treatment period average in ACQ-5 was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.	Study weeks 0, 17, 34, 52
Secondary	Average Change From Baseline in Asthma Quality of Life Questionnaire Standardised Version - AQLQ(S) Score	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. The average change from baseline to treatment period average in AQLQ(S) overall score was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.	Study weeks 0,17, 34, 52

External Links

•   D589SC00003-revised-csp-edition-4_12Oct2016_Redacted_pdfa
•   D589SC00003-statistical-analysis-plan-edition-2_06SEP2017_pdfa