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

NCT01803555 | Completed Phase 3 Results

• 1 other identifier: BFS-AS-306
• Study Type: interventional
• Target: 605
• Locations: 16 countries
• Sites: 114

Brief Summary

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.

Conditions

Asthma

Keywords

Budesonide/Formoterol SPIROMAX®; SYMBICORT® TURBOHALER®; Asthma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change From Baseline in Weekly Average of Daily Evening (PM) PEF Over the 12-Week Treatment Period

  Baseline, Weeks 1 to 12 (averaged over 12 weeks)

• Number of Participants With Adverse Events (AEs)

  Baseline up to Week 12

• Number of Participants With Signs of Oral Candidiasis (Thrush)

  Baseline, Week 4, Week 8, Week 12

• Number of Participants With Positive Swab of Oral Candidiasis (Thrush)

  Baseline, Week 4, Week 8, Week 12

Study Arms (2)

BF Spiromax

EXPERIMENTAL

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®; Drug: SYMBICORT placebo

Symbicort Turbohaler

ACTIVE COMPARATOR

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®; Drug: SPIROMAX Placebo

Interventions

Budesonide/Formoterol SPIROMAX® DRUG

BF Spiromax will be administered per dose and schedule specified in the arm.

BF Spiromax

SYMBICORT® TURBOHALER® DRUG

Symbicort Turbohaler will be administered per dose and schedule specified in the arm.

Symbicort Turbohaler

SYMBICORT placebo DRUG

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.

BF Spiromax

SPIROMAX Placebo DRUG

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.

Symbicort Turbohaler

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (114)

Teva Investigational Site 33020

Grieskirchen, 4710, Austria

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Teva Investigational Site 33019

Linz, 4020, Austria

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Teva Investigational Site 33018

Wels, 4600, Austria

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Teva Investigational Site 37029

Gozée, 6534, Belgium

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Teva Investigational Site 37031

Halen, 3545, Belgium

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Teva Investigational Site 37030

Jambes, 5100, Belgium

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Teva Investigational Site 54056

Brno, 602 00, Czechia

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Teva Investigational Site 54061

Hradec Králové, 500 05, Czechia

Location

Teva Investigational Site 54068

Neratovice, 27711, Czechia

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Teva Investigational Site 54063

Ostrava - Marianske Hory, 709 00, Czechia

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Teva Investigational Site 54065

Pilsen, 301 00, Czechia

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Teva Investigational Site 54067

Prague, 142 00, Czechia

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Teva Investigational Site 54058

Prague, 186 00, Czechia

Location

Teva Investigational Site 54064

Rokycany, 337 22, Czechia

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Teva Investigational Site 54059

Strakonice, 386 01, Czechia

Location

Teva Investigational Site 39020

Copenhagen NV, 2400, Denmark

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Teva Investigational Site 39021

Odense, 5000, Denmark

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Teva Investigational Site 40004

Helsinki, 00290, Finland

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Teva Investigational Site 40005

Jyväskylä, 40100, Finland

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Teva Investigational Site 40002

Pori, 28500, Finland

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Teva Investigational Site 40001

Tampere, 33521, Finland

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Teva Investigational Site 40003

Turku, 20100, Finland

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Teva Investigational Site 35088

Brest, 29609, France

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Teva Investigational Site 35089

La Bouëxière, 35340, France

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Teva Investigational Site 35093

Lyon, 69317, France

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Teva Investigational Site 35092

Mûrs-Erigné, 49610, France

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Teva Investigational Site 35090

Nantes, 44200, France

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Teva Investigational Site 35091

Perpignan, 66000, France

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Teva Investigational Site 32243

Berlin, 10367, Germany

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Teva Investigational Site 32255

Berlin, 10717, Germany

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Teva Investigational Site 32256

Berlin, 10787, Germany

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Teva Investigational Site 32257

Berlin, 12687, Germany

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Teva Investigational Site 32252

Cottbus, 03050, Germany

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Teva Investigational Site 32251

Frankfurt am Main, 60318, Germany

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Teva Investigational Site 32253

Frankfurt am Main, 60389, Germany

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Teva Investigational Site 32254

Gelsenkirchen, 45879, Germany

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Teva Investigational Site 32259

Großhansdorf, 22927, Germany

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Teva Investigational Site 32249

Hamburg, 20354, Germany

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Teva Investigational Site 32246

Leipzig, 4357, Germany

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Teva Investigational Site 32240

Neu-Isenburg, 63263, Germany

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Teva Investigational Site 32244

Neukölln, 12043, Germany

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Teva Investigational Site 32258

Offenbach, 63071, Germany

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Teva Investigational Site 32250

Reinfeld, 23858, Germany

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Teva Investigational Site 32241

Rüdersdorf, 15562, Germany

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Teva Investigational Site 32247

Weinheim, 69469, Germany

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Teva Investigational Site 51075

Balassagyarmat, 2660, Hungary

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Teva Investigational Site 51072

Budapest, 1134, Hungary

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Teva Investigational Site 51067

Budapest, 2310, Hungary

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Teva Investigational Site 51077

Csorna, 9300, Hungary

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Teva Investigational Site 51065

Deszk, 6772, Hungary

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Teva Investigational Site 51071

Kaposvár, 7400, Hungary

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Teva Investigational Site 51073

Kaposvár, 7400, Hungary

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Teva Investigational Site 51068

Komárom, 2900, Hungary

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Teva Investigational Site 51070

Mosdós, 7257, Hungary

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Teva Investigational Site 51076

Tatabánya, 2800, Hungary

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Teva Investigational Site 51074

Törökbálint, 2045, Hungary

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Teva Investigational Site 80036

Afula, 18101, Israel

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Teva Investigational Site 80035

Haifa, 31096, Israel

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Teva Investigational Site 80040

Kfar Saba, 44281, Israel

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Teva Investigational Site 80039

Petah Tikva, 49100, Israel

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Teva Investigational Site 80037

Ramat Gan, 5262160, Israel

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Teva Investigational Site 80038

Rehovot, 76100, Israel

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Teva Investigational Site 80041

Ẕerifin, 70300, Israel

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Teva Investigational Site 30055

Cisanello Pisa, 56124, Italy

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Teva Investigational Site 30056

Milan, 20142, Italy

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Teva Investigational Site 30054

Padua, 35122, Italy

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Teva Investigational Site 38048

Alkmaar, 1815 JD, Netherlands

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Teva Investigational Site 38049

Leeuwarden, 8901 BR, Netherlands

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Teva Investigational Site 53114

Bialystok, 15-276, Poland

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Teva Investigational Site 53110

Bialystok, 15-430, Poland

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Teva Investigational Site 53117

Gdansk, 80-433, Poland

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Teva Investigational Site 53106

Gdansk, 80-847, Poland

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Teva Investigational Site 53109

Krakow, 31-011, Poland

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Teva Investigational Site 53111

Krakow, 31-023, Poland

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Teva Investigational Site 53100

Krakow, 31-159, Poland

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Teva Investigational Site 53107

Lodz, 90-153, Poland

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Teva Investigational Site 53102

Lublin, 20-093, Poland

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Teva Investigational Site 53116

Poznan, 60-214, Poland

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Teva Investigational Site 53119

Sopot, 81-741, Poland

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Teva Investigational Site 53103

Strzelce Opolskie, 47-100, Poland

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Teva Investigational Site 53104

Szczecin, 71-124, Poland

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Teva Investigational Site 53105

Tarnów, 33-100, Poland

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Teva Investigational Site 53120

Wroclaw, 51-343, Poland

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Teva Investigational Site 53099

Wroclaw, 53-201, Poland

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Teva Investigational Site 53115

Wroclaw, 53-301, Poland

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Teva Investigational Site 53113

Zabrze, 41-800, Poland

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Teva Investigational Site 53101

Zgierz, 95-100, Poland

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Teva Investigational Site 50179

Kazan', 420015, Russia

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Teva Investigational Site 50177

Moscow, 125367, Russia

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Teva Investigational Site 50178

Saint Petersburg, 193231, Russia

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Teva Investigational Site 50175

Saint Petersburg, 194354, Russia

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Teva Investigational Site 50171

Saint Petersburg, 197022, Russia

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Teva Investigational Site 50172

Saratov, 410028, Russia

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Teva Investigational Site 50173

Tomsk, 634050, Russia

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Teva Investigational Site 50170

Vsevolozhsk, 188640, Russia

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Teva Investigational Site 50174

Yaroslavl, 150003, Russia

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Teva Investigational Site 31051

Alcorcón, 28922, Spain

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Teva Investigational Site 31054

Badalona, 08916, Spain

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Teva Investigational Site 31052

Barcelona, 08036, Spain

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Teva Investigational Site 31057

Barcelona, 08041, Spain

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Teva Investigational Site 31053

Bilbao, 48013, Spain

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Teva Investigational Site 31058

Madrid, 28006, Spain

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Teva Investigational Site 31056

Pamplona, 31008, Spain

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Teva Investigational Site 31055

Seville, 41013, Spain

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Teva Investigational Site 31061

Vitoria-Gasteiz, 01004, Spain

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Teva Investigational Site 42014

Gothenburg, 413 45, Sweden

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Teva Investigational Site 42011

Lund, 222 41, Sweden

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Teva Investigational Site 42012

Stockholm, 141 86, Sweden

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Teva Investigational Site 34024

Chesterfield, S40 4AA, United Kingdom

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Teva Investigational Site 34026

Coventry, CV6 4DD, United Kingdom

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Teva Investigational Site 34022

Dundee, DD1 4HJ, United Kingdom

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Teva Investigational Site 34027

East Sussex, TN40 1JJ, United Kingdom

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Teva Investigational Site 34029

Lancashire, FY4 3AD, United Kingdom

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Teva Investigational Site 34028

London, EC1M 6BQ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 26987997 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Budesonide

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products R&D, Inc.

USMedInfo@tevapharm.com

1-888-483-8279

Study Officials

• Teva Medical Expert, M.D.

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: February 28, 2013
• First Posted: March 4, 2013
• Study Start: July 4, 2013
• Primary Completion: March 20, 2014
• Study Completion: March 20, 2014
• Last Updated: December 8, 2023
• Results First Posted: December 8, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share

Locations

GB (6); PL (19); CZ (9); HU (11); IL (7); IT (3); BE (3); FI (5); SE (3); RU (9); NL (2); DE (17); AU (3); FR (6); ES (9); DK (2)