Efficacy and Safety of Tiotropium and Salmeterol in Moderate Persistent Asthma Patients Homozygous for B16-Arg/Arg

NCT00350207 | Completed Phase 2 Results

• 1 other identifier: 205.342
• Study Type: interventional
• Target: 388
• Locations: 14 countries
• Sites: 109

Brief Summary

This is a 16 week multicentre, multinational, randomised, double-blind, double-dummy, placebo-controlled, parallel group study to evaluate the long-term efficacy and safety of tiotropium compared to salmeterol in moderate persistent asthmatic (GINA step 3) patients homozygous for arginine at the 16th amino acid position of the beta-adrenergic receptor (ADRB2). Following an initial 4-week run-in period on salmeterol MDI patients will be randomised into the 16 week double-blind treatment period in which they receive either tiotropium once daily administered from the Respimat inhaler or salmeterol twice daily administered from the hydrofluoro-alkane Metered Dose Inhaler (MDI), or placebo twice daily. After the 16 week treatment period all patients will receive salmeterol MDI twice daily for four weeks. The patients perform daily morning and evening peak flow (PEF) and Forced Expiratory Volume in the First Second (FEV1) measurements with an electronic peak flow meter throughout the study. Daily data on asthma control and use of rescue medication are recorded using an electronic diary included in the electronic peak flow meter. On study visits the Mini-Asthma Quality of Life Questionnaire (Elizabeth Juniper) is administered, pulse and blood pressure and pre-dose pulmonary function testing (FEV1 and Forced Vital Capacity) are performed.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Change in Mean Weekly Morning Peak Expiratory Flow From Baseline to the End of the Trial

  Change from baseline in mean weekly morning peak expiratory flow at 16 weeks. Baseline is defined as the last week prior to the randomisation visit

  baseline and after 16 weeks of treatment

Secondary Outcomes (62)

• Mean Weekly Morning Peak Expiratory Flow at Week 4

  After 4 weeks of treatment

• Mean Weekly Morning Peak Expiratory Flow at Week 8

  After 8 weeks of treatment

• Mean Weekly Morning Peak Expiratory Flow at Week 12

  After 12 weeks of treatment

• Mean Weekly Morning Peak Expiratory Flow at Week 16

  After 16 weeks of treatment

• Mean Weekly Evening Peak Expiratory Flow at Week 4

  After 4 weeks of treatment

Interventions

Tiotropium bromide DRUG

Placebo DRUG

Salmeterol xinafoate DRUG

Eligibility Criteria

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

Inclusion\_Criteria: 1. Patients homozygous for arginine at the 16th amino acid position of the beta2 adrenergic receptor (B16 Arg/Arg) 2. All patients must sign and date an Informed Consent Form for the study prior to participation in the trial 3. Male or female outpatients with at least 18 years of age, but not older than 65 years 4. Patients must have a documented history of asthma 5. Patients must be current non-smokers or ex-smokers with a cigarette smoking history of \<10 pack-years 6. Patients must be on a maintenance treatment with inhaled corticosteroids with a total daily dose of 400 - 1000 mcg budesonide or equivalent Exclusion\_Criteria: 1. Patients with a significant disease other than asthma 2. Patients with a recent history (i.e., six months or less) of myocardial infarction 3. Patients who have been hospitalized for heart failure (New York Heart Association class III or IV) within the past year 4. Patients with any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year 5. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years. Patients with treated basal cell carcinoma are allowed. 6. Patients with a diagnosis of chronic obstructive pulmonary disease (COPD) 7. Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis 8. Patients with known active tuberculosis 9. Patients who have undergone thoracotomy with pulmonary resection. 10. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to visit 1 or patients who are currently in a pulmonary rehabilitation program that will not be maintained throughout the duration of the study.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (109)

205.342.43002 Boehringer Ingelheim Investigational Site

Graz, Austria

Location

205.342.43004 Boehringer Ingelheim Investigational Site

Trofaiach, Austria

Location

205.342.43001 Boehringer Ingelheim Investigational Site

Vienna, Austria

Location

205.342.43005 Boehringer Ingelheim Investigational Site

Vienna, Austria

Location

205.342.43006 Boehringer Ingelheim Investigational Site

Vienna, Austria

Location

205.342.43007 Boehringer Ingelheim Investigational Site

Vienna, Austria

Location

205.342.43003 Boehringer Ingelheim Investigational Site

Wels, Austria

Location

205.342.32010 Boehringer Ingelheim Investigational Site

Anderlecht, Belgium

Location

205.342.32005 Boehringer Ingelheim Investigational Site

Angleur, Belgium

Location

205.342.32002 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

205.342.32007 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

205.342.32014 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

205.342.32001 Boehringer Ingelheim Investigational Site

Ghent, Belgium

Location

205.342.32003 Boehringer Ingelheim Investigational Site

Herentals, Belgium

Location

205.342.32004 Boehringer Ingelheim Investigational Site

Malmedy, Belgium

Location

205.342.32012 Boehringer Ingelheim Investigational Site

Menen, Belgium

Location

205.342.32006 Boehringer Ingelheim Investigational Site

Montigny-le-Tilleul, Belgium

Location

205.342.32009 Boehringer Ingelheim Investigational Site

Namur, Belgium

Location

205.342.32011 Boehringer Ingelheim Investigational Site

Turnhout, Belgium

Location

205.342.32013 Boehringer Ingelheim Investigational Site

Yvoir, Belgium

Location

205.342.45003 Boehringer Ingelheim Investigational Site

Aalborg, Denmark

Location

205.342.45001 Boehringer Ingelheim Investigational Site

Hvidovre, Denmark

Location

205.342.45002 Boehringer Ingelheim Investigational Site

København NV, Denmark

Location

205.342.45004 Boehringer Ingelheim Investigational Site

Odense C, Denmark

Location

205.342.35803 Boehringer Ingelheim Investigational Site

Helsinki, Finland

Location

205.342.35801 Boehringer Ingelheim Investigational Site

Jyväskylä, Finland

Location

205.342.35802 Boehringer Ingelheim Investigational Site

Lahti, Finland

Location

205.342.35804 Boehringer Ingelheim Investigational Site

Tampere, Finland

Location

205.342.3305A Centre Hosp de la Cavale Blanche

Brest, France

Location

205.342.3304A Cabinet Médical

Chamalières, France

Location

205.342.3307A Boehringer Ingelheim Investigational Site

Chauny, France

Location

205.342.3301A UCP-X - Clinique Médicale

Grenoble, France

Location

205.342.3302A Hôpital Arnaud de Villeneuve

Montpellier, France

Location

205.342.3306A Mediscis

Poitiers, France

Location

205.342.3308A Boehringer Ingelheim Investigational Site

Saint Pierre La Réunion, France

Location

205.342.3308B Boehringer Ingelheim Investigational Site

Saint Pierre La Réunion, France

Location

205.342.49016 Boehringer Ingelheim Investigational Site

Beelitz-Heilstätten, Germany

Location

205.342.49004 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

205.342.49006 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

205.342.49013 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

205.342.49003 Boehringer Ingelheim Investigational Site

Bruchsal, Germany

Location

205.342.49009 Boehringer Ingelheim Investigational Site

Cologne, Germany

Location

205.342.49011 Boehringer Ingelheim Investigational Site

Frankfurt am Main, Germany

Location

205.342.49007 Boehringer Ingelheim Investigational Site

Kassel, Germany

Location

205.342.49010 Boehringer Ingelheim Investigational Site

Mainz, Germany

Location

205.342.49008 Boehringer Ingelheim Investigational Site

Minden, Germany

Location

205.342.49015 Boehringer Ingelheim Investigational Site

Neuruppin, Germany

Location

205.342.49012 Boehringer Ingelheim Investigational Site

Rathenow, Germany

Location

205.342.49005 Boehringer Ingelheim Investigational Site

Rüdersdorf, Germany

Location

205.342.49002 Boehringer Ingelheim Investigational Site

Weinheim, Germany

Location

205.342.30001 Boehringer Ingelheim Investigational Site

Athens, Greece

Location

205.342.30002 Boehringer Ingelheim Investigational Site

Athens, Greece

Location

205.342.30005 Boehringer Ingelheim Investigational Site

Heraklion, Greece

Location

205.342.30006 Boehringer Ingelheim Investigational Site

Kavala, Greece

Location

205.342.30004 Boehringer Ingelheim Investigational Site

Larissa, Greece

Location

205.342.30003 Boehringer Ingelheim Investigational Site

Thessaloniki, Greece

Location

205.342.39003 Azienda Ospedaliera " S. Anna"

Ferrara, Italy

Location

205.342.39006 Azienda Ospedaliera Universitaria Careggi

Florence, Italy

Location

205.342.39005 Ospedale San Martino

Genova, Italy

Location

205.342.39002 Università di Modena e Reggio Emilia

Modena, Italy

Location

205.342.39010 Boehringer Ingelheim Investigational Site

Orbassano (to), Italy

Location

205.342.39007 Policlinico San Matteo

Pavia, Italy

Location

205.342.39001 Ospedale di Cisanello

Pisa, Italy

Location

205.342.39009 Boehringer Ingelheim Investigational Site

Sesto San Giovanni (mi), Italy

Location

205.342.07001 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.342.07002 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.342.07003 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.342.07004 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.342.07005 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.342.07006 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.342.07007 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.342.07008 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.342.42101 Boehringer Ingelheim Investigational Site

Banská Bystrica, Slovakia

Location

205.342.42102 Boehringer Ingelheim Investigational Site

Bratislava, Slovakia

Location

205.342.42104 Boehringer Ingelheim Investigational Site

Bratislava, Slovakia

Location

205.342.42105 Boehringer Ingelheim Investigational Site

Bratislava, Slovakia

Location

205.342.42107 Boehringer Ingelheim Investigational Site

Bratislava, Slovakia

Location

205.342.42103 Boehringer Ingelheim Investigational Site

Košice, Slovakia

Location

205.342.42106 Boehringer Ingelheim Investigational Site

Trenčín, Slovakia

Location

205.342.42108 Boehringer Ingelheim Investigational Site

Žilina, Slovakia

Location

205.342.27002 Boehringer Ingelheim Investigational Site

Bellville, South Africa

Location

205.342.27008 Boehringer Ingelheim Investigational Site

Bloemfontein, South Africa

Location

205.342.27001 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

205.342.27004 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

205.342.27006 Boehringer Ingelheim Investigational Site

Centurion, South Africa

Location

205.342.27003 Boehringer Ingelheim Investigational Site

Durban, South Africa

Location

205.342.27007 Boehringer Ingelheim Investigational Site

George, South Africa

Location

205.342.27005 Boehringer Ingelheim Investigational Site

Pretoria, South Africa

Location

205.342.34006 Hospital Clinic i Provincial de Barcelona

Barcelona, Spain

Location

205.342.34011 Boehringer Ingelheim Investigational Site

Centelles, Spain

Location

205.342.34004 Hospital General Universitario de Guadalajara

Guadalajara, Spain

Location

205.342.34002 Hospital de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, Spain

Location

205.342.34007 Hospital Universitari Arnau de Vilanova

Lleida, Spain

Location

205.342.34003 Hospital Universitario La Paz

Madrid, Spain

Location

205.342.34009 Hospital Universio Puerta del Hierro

Madrid, Spain

Location

205.342.34008 Hospital Universitario Marqués de Valdecilla

Santander, Spain

Location

205.342.34005 Hospital Vírgen de la Macarena

Seville, Spain

Location

205.342.34010 Hospital General Universitario de Valencia

Valencia, Spain

Location

205.342.90001 Boehringer Ingelheim Investigational Site

Ankara, Turkey (Türkiye)

Location

205.342.90006 Boehringer Ingelheim Investigational Site

Ankara, Turkey (Türkiye)

Location

205.342.90003 Boehringer Ingelheim Investigational Site

Bursa, Turkey (Türkiye)

Location

205.342.90007 Istanbul Universitesi Cerrahpasa Tip Fakultesi

Istanbul, Turkey (Türkiye)

Location

205.342.90005 Kocaeli Universitesi Tip Fakultesi

İzmit, Turkey (Türkiye)

Location

205.342.90004 Celal Bayar Universitesi Tip Fakultesi

Manisa, Turkey (Türkiye)

Location

205.342.44002 Boehringer Ingelheim Investigational Site

Aylesbury, United Kingdom

Location

205.342.44001 Boehringer Ingelheim Investigational Site

Chertsey, United Kingdom

Location

205.342.44003 Boehringer Ingelheim Investigational Site

Greenisland, United Kingdom

Location

205.342.44006 Boehringer Ingelheim Investigational Site

Leicester, United Kingdom

Location

205.342.44005 Boehringer Ingelheim Investigational Site

Nottingham, United Kingdom

Location

Related Publications (2)

• Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.

  PMID: 36472162 DERIVED

• Bateman ED, Kornmann O, Schmidt P, Pivovarova A, Engel M, Fabbri LM. Tiotropium is noninferior to salmeterol in maintaining improved lung function in B16-Arg/Arg patients with asthma. J Allergy Clin Immunol. 2011 Aug;128(2):315-22. doi: 10.1016/j.jaci.2011.06.004.

  PMID: 21807250 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Tiotropium Bromide; Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Boehringer Ingelheim Pharmaceuticals
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 7, 2006
• First Posted: July 10, 2006
• Study Start: July 1, 2006
• Primary Completion: September 1, 2008
• Last Updated: December 24, 2013
• Results First Posted: November 17, 2009

Record last verified: 2013-09

Locations

DK (4); GR (6); BE (13); FI (4); FR (8); IT (8); RU (8); AU (7); DE (14); ES (10); GB (5); SL (8); ZA (8); TU (6)