Efficacy and Safety Evaluation of Budesonide/Formoterol SPIROMAX® Inhalation Powder Versus SYMBICORT® TURBOHALER®

A 12-Week Efficacy and Safety Evaluation of Budesonide/Formoterol SPIROMAX(R) 160/4.5 mcg Inhalation Powder Versus SYMBICORT(R) TURBOHALER(R) 200/6 mcg in Adult and Adolescent Patients With Persistent Asthma

The primary objective of the study is to establish whether budesonide/formoterol fumarate dihydrate (BF) Spiromax 160/4.5 micrograms (mcg) is as effective as Symbicort Turbohaler 200/6 mcg administered twice daily in participants with persistent asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Budesonide/Formoterol SPIROMAX®; Drug: SYMBICORT placebo; Drug: SYMBICORT® TURBOHALER®; Drug: SPIROMAX Placebo

• Study Type: Interventional
• Enrollment (Actual): 605
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Grieskirchen, Austria, 4710
    • Teva Investigational Site 33020
  • Linz, Austria, 4020
    • Teva Investigational Site 33019
  • Wels, Austria, 4600
    • Teva Investigational Site 33018
• Belgium
  • Gozee, Belgium, 6534
    • Teva Investigational Site 37029
  • Halen, Belgium, 3545
    • Teva Investigational Site 37031
  • Jambes, Belgium, 5100
    • Teva Investigational Site 37030
• Czechia
  • Brno, Czechia, 602 00
    • Teva Investigational Site 54056
  • Hradec Kralove, Czechia, 500 05
    • Teva Investigational Site 54061
  • Neratovice, Czechia, 27711
    • Teva Investigational Site 54068
  • Ostrava - Marianske Hory, Czechia, 709 00
    • Teva Investigational Site 54063
  • Plzen, Czechia, 301 00
    • Teva Investigational Site 54065
  • Praha, Czechia, 142 00
    • Teva Investigational Site 54067
  • Praha, Czechia, 186 00
    • Teva Investigational Site 54058
  • Rokycany, Czechia, 337 22
    • Teva Investigational Site 54064
  • Strakonice, Czechia, 386 01
    • Teva Investigational Site 54059
• Denmark
  • Copenhagen NV, Denmark, 2400
    • Teva Investigational Site 39020
  • Odense, Denmark, 5000
    • Teva Investigational Site 39021
• Finland
  • Helsinki, Finland, 00290
    • Teva Investigational Site 40004
  • Jyvaskyla, Finland, 40100
    • Teva Investigational Site 40005
  • Pori, Finland, 28500
    • Teva Investigational Site 40002
  • Tampere, Finland, 33521
    • Teva Investigational Site 40001
  • Turku, Finland, 20100
    • Teva Investigational Site 40003
• France
  • Brest Cedex 2, France, 29609
    • Teva Investigational Site 35088
  • La Bouexiere, France, 35340
    • Teva Investigational Site 35089
  • Lyon Cedex 04, France, 69317
    • Teva Investigational Site 35093
  • Murs Erigne, France, 49610
    • Teva Investigational Site 35092
  • Nantes, France, 44200
    • Teva Investigational Site 35090
  • Perpignan, France, 66000
    • Teva Investigational Site 35091
• Germany
  • Berlin, Germany, 10367
    • Teva Investigational Site 32243
  • Berlin, Germany, 10717
    • Teva Investigational Site 32255
  • Berlin, Germany, 10787
    • Teva Investigational Site 32256
  • Berlin, Germany, 12687
    • Teva Investigational Site 32257
  • Berlin-Neukolln, Germany, 12043
    • Teva Investigational Site 32244
  • Cottbus, Germany, 03050
    • Teva Investigational Site 32252
  • Frankfurt am Main, Germany, 60318
    • Teva Investigational Site 32251
  • Frankfurt/Main, Germany, 60389
    • Teva Investigational Site 32253
  • Gelsenkirchen, Germany, 45879
    • Teva Investigational Site 32254
  • Grosshansdorf, Germany, 22927
    • Teva Investigational Site 32259
  • Hamburg, Germany, 20354
    • Teva Investigational Site 32249
  • Leipzig, Germany, 4357
    • Teva Investigational Site 32246
  • Neu-Isenburg, Germany, 63263
    • Teva Investigational Site 32240
  • Offenbach, Germany, 63071
    • Teva Investigational Site 32258
  • Reinfeld, Germany, 23858
    • Teva Investigational Site 32250
  • Rudersdorf, Germany, 15562
    • Teva Investigational Site 32241
  • Weinheim, Germany, 69469
    • Teva Investigational Site 32247
• Hungary
  • Balassagyarmat, Hungary, 2660
    • Teva Investigational Site 51075
  • Budapest, Hungary, 1134
    • Teva Investigational Site 51072
  • Budapest, Hungary, 2310
    • Teva Investigational Site 51067
  • Csorna, Hungary, 9300
    • Teva Investigational Site 51077
  • Deszk, Hungary, 6772
    • Teva Investigational Site 51065
  • Kaposvar, Hungary, 7400
    • Teva Investigational Site 51071
  • Kaposvar, Hungary, 7400
    • Teva Investigational Site 51073
  • Komarom, Hungary, 2900
    • Teva Investigational Site 51068
  • Mosdos, Hungary, 7257
    • Teva Investigational Site 51070
  • Tatabanya, Hungary, 2800
    • Teva Investigational Site 51076
  • Torokbalint, Hungary, 2045
    • Teva Investigational Site 51074
• Israel
  • Afula, Israel, 18101
    • Teva Investigational Site 80036
  • Haifa, Israel, 31096
    • Teva Investigational Site 80035
  • Kfar Saba, Israel, 44281
    • Teva Investigational Site 80040
  • Petach Tikva, Israel, 49100
    • Teva Investigational Site 80039
  • Ramat Gan, Israel, 5262160
    • Teva Investigational Site 80037
  • Rehovot, Israel, 76100
    • Teva Investigational Site 80038
  • Zerifin, Israel, 70300
    • Teva Investigational Site 80041
• Italy
  • Cisanello Pisa, Italy, 56124
    • Teva Investigational Site 30055
  • Milano, Italy, 20142
    • Teva Investigational Site 30056
  • Padova, Italy, 35122
    • Teva Investigational Site 30054
• Netherlands
  • Alkmaar, Netherlands, 1815 JD
    • Teva Investigational Site 38048
  • Leeuwarden, Netherlands, 8901 BR
    • Teva Investigational Site 38049
• Poland
  • Bialystok, Poland, 15-276
    • Teva Investigational Site 53114
  • Bialystok, Poland, 15-430
    • Teva Investigational Site 53110
  • Gdansk, Poland, 80-433
    • Teva Investigational Site 53117
  • Gdansk, Poland, 80-847
    • Teva Investigational Site 53106
  • Krakow, Poland, 31-011
    • Teva Investigational Site 53109
  • Krakow, Poland, 31-023
    • Teva Investigational Site 53111
  • Krakow, Poland, 31-159
    • Teva Investigational Site 53100
  • Lodz, Poland, 90-153
    • Teva Investigational Site 53107
  • Lublin, Poland, 20-093
    • Teva Investigational Site 53102
  • Poznan, Poland, 60-214
    • Teva Investigational Site 53116
  • Sopot, Poland, 81-741
    • Teva Investigational Site 53119
  • Strzelce Opolskie, Poland, 47-100
    • Teva Investigational Site 53103
  • Szczecin, Poland, 71-124
    • Teva Investigational Site 53104
  • Tarnow, Poland, 33-100
    • Teva Investigational Site 53105
  • Wroclaw, Poland, 51-343
    • Teva Investigational Site 53120
  • Wroclaw, Poland, 53-201
    • Teva Investigational Site 53099
  • Wroclaw, Poland, 53-301
    • Teva Investigational Site 53115
  • Zabrze, Poland, 41-800
    • Teva Investigational Site 53113
  • Zgierz, Poland, 95-100
    • Teva Investigational Site 53101
• Russian Federation
  • Kazan, Russian Federation, 420015
    • Teva Investigational Site 50179
  • Moscow, Russian Federation, 125367
    • Teva Investigational Site 50177
  • Saint Petersburg, Russian Federation, 197022
    • Teva Investigational Site 50171
  • Saint-Petersburg, Russian Federation, 194354
    • Teva Investigational Site 50175
  • Saratov, Russian Federation, 410028
    • Teva Investigational Site 50172
  • St. Petersburg, Russian Federation, 193231
    • Teva Investigational Site 50178
  • Tomsk, Russian Federation, 634050
    • Teva Investigational Site 50173
  • Vsevolozhsk, Russian Federation, 188640
    • Teva Investigational Site 50170
  • Yaroslavl, Russian Federation, 150003
    • Teva Investigational Site 50174
• Spain
  • Alcorcon, Spain, 28922
    • Teva Investigational Site 31051
  • Badalona, Spain, 08916
    • Teva Investigational Site 31054
  • Barcelona, Spain, 08036
    • Teva Investigational Site 31052
  • Barcelona, Spain, 08041
    • Teva Investigational Site 31057
  • Bilbao, Spain, 48013
    • Teva Investigational Site 31053
  • Madrid, Spain, 28006
    • Teva Investigational Site 31058
  • Pamplona, Spain, 31008
    • Teva Investigational Site 31056
  • Sevilla, Spain, 41013
    • Teva Investigational Site 31055
  • Vitoria, Spain, 01004
    • Teva Investigational Site 31061
• Sweden
  • Goteborg, Sweden, 413 45
    • Teva Investigational Site 42014
  • Lund, Sweden, 222 41
    • Teva Investigational Site 42011
  • Stockholm, Sweden, 141 86
    • Teva Investigational Site 42012
• United Kingdom
  • Chesterfield, United Kingdom, S40 4AA
    • Teva Investigational Site 34024
  • Coventry, United Kingdom, CV6 4DD
    • Teva Investigational Site 34026
  • Dundee, United Kingdom, DD1 4HJ
    • Teva Investigational Site 34022
  • East Sussex, United Kingdom, TN40 1JJ
    • Teva Investigational Site 34027
  • Lancashire, United Kingdom, FY4 3AD
    • Teva Investigational Site 34029
  • London, United Kingdom, EC1M 6BQ
    • Teva Investigational Site 34028

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female participants 12 years and older as of the screening visit. Male or female participants 18 years and older, as of the screening visit, in countries where local regulations or the regulatory status of study medication permit enrollment of adult participants only.
• General good health, and free of any concomitant conditions or treatment that could interfere with study conduct, influence the interpretation of study observations/results, or put the participant at increased risk during the study.
• Asthma Diagnosis: The asthma diagnosis must be in accordance with the Global Initiative for Asthma (GINA)

Exclusion Criteria:

• History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures.
• Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that is not resolved within 2 weeks before the screening visit. In addition, the participant must be excluded if such infection occurs between the screening visit and the baseline visit.
• Any asthma exacerbation requiring oral corticosteroids within 1 month of the screening visit. A participant must not have been hospitalized for asthma within 6 months before the screening visit.
• Presence of glaucoma, cataracts, ocular herpes simplex, or malignancy other than basal cell carcinoma.
• Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular conditions (for example, congestive heart failure, known aortic aneurysm, clinically significant cardiac arrhythmia or coronary heart disease), hepatic, renal, hematological, neuropsychological, endocrine conditions (for example, uncontrolled diabetes mellitus, uncontrolled thyroid disorder, Addison's disease, Cushing's syndrome), gastrointestinal conditions (for example, poorly-controlled peptic ulcer, gastroesophageal reflux disease [GERD]), or pulmonary conditions (for example, chronic bronchitis, emphysema, bronchiectasis with the need for treatment, cystic fibrosis, bronchopulmonary dysplasia, chronic obstructive pulmonary disease). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the participant at risk through participation, or which could affect the efficacy or safety analysis if the disease/condition became exacerbated during the study.

NOTE: Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BF Spiromax; 2 inhalations of BF Spiromax at a dosage of 160/4.5 mcg and 2 inhalations of SYMBICORT placebo administered twice daily (AM and PM) during the 12-week treatment period.	Drug: Budesonide/Formoterol SPIROMAX®; BF Spiromax will be administered per dose and schedule specified in the arm.; Drug: SYMBICORT placebo; SYMBICORT placebo multi-dose dry powder inhaler (DPI) identical in appearance to SYMBICORT TURBOHALER will be administered per dose and schedule specified in the arm.
Active Comparator: Symbicort Turbohaler; 2 inhalations of SYMBICORT TURBOHALER at a dosage of 200/6 mcg and 2 inhalations of placebo SPIROMAX administered twice daily (AM and PM) during the 12-week treatment period.	Drug: SYMBICORT® TURBOHALER®; Symbicort Turbohaler will be administered per dose and schedule specified in the arm.; Drug: SPIROMAX Placebo; SPIROMAX Placebo multi-dose dry powder inhaler (DPI) identical in appearance to BF SPIROMAX will be administered per dose and schedule specified in the arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weekly Average of Daily Trough (Predose and Pre-rescue Bronchodilator) Morning (AM) Peak Expiratory Flow (PEF) Over the 12-Week Treatment Period	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Baseline trough morning PEF was defined as the average value of recorded (nonmissing) morning assessments 5 out of the last 7 days prior to randomization. The first day before randomization consisted of the electronic patient diary entry at home on the morning of the randomization visit (Baseline [Day 1]) and the first day postrandomization consisted of the electronic patient diary entry at home on the morning of the day after the randomization visit (Baseline [Day 1]). For postdose weekly average of trough morning PEF measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of morning PEF values divided by the number of nonmissing assessments. The final value for change from baseline was calculated as the average of the weekly change from baseline averaged over 12 weeks.	Baseline, Weeks 1 to 12 (averaged over 12 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weekly Average of Daily Evening (PM) PEF Over the 12-Week Treatment Period	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Baseline was defined as the average value of the recorded (nonmissing) assessments over the 7 days prior to randomization. For postdose weekly average of evening PEF measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of evening PEF values divided by the number of nonmissing assessments. The final value for change from baseline was calculated as the average of the weekly change from baseline averaged over 12 weeks.	Baseline, Weeks 1 to 12 (averaged over 12 weeks)
Number of Participants With Adverse Events (AEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.	Baseline up to Week 12
Number of Participants With Signs of Oral Candidiasis (Thrush)	Examinations were performed by a qualified professional.	Baseline, Week 4, Week 8, Week 12
Number of Participants With Positive Swab of Oral Candidiasis (Thrush)	Swab samples were collected by a qualified professional.	Baseline, Week 4, Week 8, Week 12

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Investigators: Study Director: Teva Medical Expert, M.D., Teva Branded Pharmaceutical Products R&D, Inc.

Publications and helpful links

General Publications

• Virchow JC, Rodriguez-Roisin R, Papi A, Shah TP, Gopalan G. A randomized, double-blinded, double-dummy efficacy and safety study of budesonide-formoterol Spiromax(R) compared to budesonide-formoterol Turbuhaler(R) in adults and adolescents with persistent asthma. BMC Pulm Med. 2016 Mar 17;16:42. doi: 10.1186/s12890-016-0200-x.

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2013
• Primary Completion (Actual): March 20, 2014
• Study Completion (Actual): March 20, 2014

Study Registration Dates

• First Submitted: February 28, 2013
• First Submitted That Met QC Criteria: March 1, 2013
• First Posted (Estimated): March 4, 2013

Study Record Updates

• Last Update Posted (Estimated): December 8, 2023
• Last Update Submitted That Met QC Criteria: March 6, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Asthma; Budesonide/Formoterol SPIROMAX®; SYMBICORT® TURBOHALER®
• 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; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Budesonide; Formoterol Fumarate; Budesonide, Formoterol Fumarate Drug Combination
• Other Study ID Numbers: BFS-AS-306

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be reviewed for scientific merit, product approval status, and conflicts of interest. Patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please email USMedInfo@tevapharm.com to make your request.