Efficacy and Safety of 2 Doses of Tiotropium Via Respimat in Adult Patients With Mild Persistent Asthma

NCT01316380 | Completed Phase 3 Results

• 2 other identifiers: 205.4422010-023112-14
• Study Type: interventional
• Target: 465
• Locations: 12 countries
• Sites: 62

Brief Summary

The aim of this trial is to evaluate the efficacy and safety of 2.5 and 5 mcg tiotropium compared to placebo over 12 week treatment period. Tiotropium inhalation solution will be delivered via Respimat inhaler and will be examined on top of maintenance inhaled corticosteroid treatment in patients with mild persistent asthma. Efficacy and safety will be assessed by measuring the effects on lung functions, effects on lung exacerbations, effects on asthma control and numbers of adverse events.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Peak Forced Expiratory Volume in 1 Second (FEV1) Response Within 3 Hours Post Dosing (0-3h) After a Treatment Period of 12 Weeks.

  Peak FEV1 0-3h response was defined as the difference between the maximum FEV1 measured within the first 3 hours post dosing after a treatment period of 12 weeks and the FEV1 baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, pooled centre, visit, baseline, treatment\*visit and baseline\*visit.

  Baseline and 12 weeks

Secondary Outcomes (10)

• Trough FEV1 Response Determined After a Treatment Period of 12 Weeks.

  Baseline and 12 weeks

• Peak (Within 3 Hours Post-dosing) Forced Vital Capacity (FVC) Response at the End of the 12-week Treatment Period.

  Baseline and 12 weeks

• FEV1 Area Under the Curve (AUC0-3h) Response at the End of the 12-week Treatment Period.

  Baseline and 12 weeks

• FVC (AUC0-3h) Response at the End of the 12-week Treatment Period.

  Baseline and 12 weeks

• Asthma Control Questionnaire (ACQ) Responder After 12 Weeks of Treatment

  12 weeks

Study Arms (3)

tiotropium 5 mcg

EXPERIMENTAL

once daily delivered via Respimat inhaler

Drug: tiotropium 5 mcg

tiotropium 2.5 mcg

EXPERIMENTAL

once daily delivered via Respimat inhaler

Drug: tiotropium 2.5 mcg

placebo

PLACEBO COMPARATOR

once daily delivered via Respimat inhaler

Drug: placebo

Interventions

placebo DRUG

To evaluate efficacy and safety of 2.5 and 5 mcg tiotropium versus placebo delivered via Respimat inhaler

placebo

tiotropium 2.5 mcg DRUG

To evaluate efficacy and safety of 2.5 and 5 mcg tiotropium versus placebo delivered via Respimat inhaler

tiotropium 2.5 mcg

tiotropium 5 mcg DRUG

To evaluate efficacy and safety of 2.5 and 5 mcg tiotropium versus placebo delivered via Respimat inhaler

tiotropium 5 mcg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must sign and date an Informed Consent Form consistent with International Conference on Harmonisation -Good Clinical Practice (ICH-GCP) guidelines and local legislation prior to participation in the trial (i.e. prior to any trial procedures, including any pre-trial washout of medications and medication restrictions for pulmonary function test at Visit 1).
• Male or female patients aged 18 years or more at Visit 0 and 75 years or less at Visit 0.
• All patients must have
• at least a 3 months history of asthma at the time of enrolment into the trial. The initial diagnosis of asthma must have been made before the patient's age of 40;
• a pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1)= 60% predicted and = 90% of predicted normal at Visit 1. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%.
• Patient's diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility (within 10 minutes pre and 15-30 minutes after 400 µg salbutamol/albuterol) resulting in a FEV1 increase of = 12% and = 200mL. If this is not achieved the reversibility test may be repeated once within two weeks.
• All patients must be symptomatic despite their current maintenance treatment with low doses of inhaled corticosteroids.
• All patients must be symptomatic at Visit 1 (screening) and Visit 2 as defined by an Asthma Control Questionnaire (ACQ) mean score of = 1.5.
• All patients must have been on maintenance treatment with a low, stable dose of inhaled corticosteroids for at least 4 weeks prior to Visit 1.
• Patients must be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment and who have a smoking history of less than 10 pack years ((see Appendix 10.3 for calculation).
• Patients must be able to use the Respimat® inhaler correctly.
• Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of the e-Diary/peak flow meter (e-Diary-compliance of at least 80% is required; refer to Section 6.2.1 for instructions).
• Patients taking a chronic pulmonary medication allowed by the study protocol must be willing to continue this therapy for the entire duration of the study (exception: times of acute disease deterioration).

You may not qualify if:

• Patients with a significant disease other than asthma. A significant disease is defined as a disease which, in the opinion of the Investigator, may (i) put the patient at risk because of participation in the trial, or (ii) cause concern regarding the patient's ability to participate in the trial.
• Patients requiring more than 10 puffs of rescue medication (salbutamol/albuterol MDI) per 24 hours on 2 consecutive days during the screening period.
• Patients with a recent history (i.e. six months or less) of Acute Coronary Syndrome (STEMI, Non-STEMI and Unstable Angina Pectoris).
• Patients who have been hospitalised for cardiac failure during the past year.
• Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year.
• Patients with lung diseases other than asthma (e.g. COPD).
• Patients with known active tuberculosis.
• 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.
• Patients with significant alcohol or drug abuse on Investigator's assessment within the past two years.
• Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to Visit 1 (screening).
• Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the tiotropium inhalation solution.
• Pregnant or nursing woman, including female patients with positive beta-HCG test at Visit 1.
• Female patients of child-bearing potential not using highly effective method of birth control As defined in ICH (M3).
• Patients who have been treated with beta-blocker medication within four weeks prior to Visit 1 and/or during the screening period.Topical cardio-selective beta-blocker eye medications for non-narrow angle glaucoma are allowed.
• Patients who have been treated with oral or patch beta-adrenergics, systemic, i.e. oral or intravenous corticosteroids, long-acting anticholinergic tiotropium (Spiriva®) within four weeks prior to Visit 1 and/or during the screening period.

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Pfizer: collaborator

Study Sites (62)

205.442.54002 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

205.442.54005 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

205.442.54003 Boehringer Ingelheim Investigational Site

San Juan Bautista, Argentina

Location

205.442.43002 Boehringer Ingelheim Investigational Site

Linz, Austria

Location

205.442.43003 Boehringer Ingelheim Investigational Site

Schlüsslberg, Austria

Location

205.442.43001 Boehringer Ingelheim Investigational Site

Wels, Austria

Location

205.442.38502 Boehringer Ingelheim Investigational Site

Rijeka, Croatia

Location

205.442.38501 Boehringer Ingelheim Investigational Site

Split, Croatia

Location

205.442.38503 Boehringer Ingelheim Investigational Site

Split, Croatia

Location

205.442.38504 Boehringer Ingelheim Investigational Site

Zagreb, Croatia

Location

205.442.37203 Boehringer Ingelheim Investigational Site

Kohtla-Järve, Estonia

Location

205.442.37201 Boehringer Ingelheim Investigational Site

Rakvere, Estonia

Location

205.442.37202 Boehringer Ingelheim Investigational Site

Tartu, Estonia

Location

205.442.50203 Boehringer Ingelheim Investigational Site

Guatemala City, Guatemala

Location

205.442.50204 Boehringer Ingelheim Investigational Site

Guatemala City, Guatemala

Location

205.442.50201 Boehringer Ingelheim Investigational Site

Nivel Guatemala, Guatemala

Location

205.442.50202 Boehringer Ingelheim Investigational Site

Nivel Guatemala, Guatemala

Location

205.442.50205 Boehringer Ingelheim Investigational Site

Vila Hermosa I, Guatemala

Location

205.442.36007 Boehringer Ingelheim Investigational Site

Budapest, Hungary

Location

205.442.36003 Boehringer Ingelheim Investigational Site

Cegléd, Hungary

Location

205.442.36002 Boehringer Ingelheim Investigational Site

Gödöllö, Hungary

Location

205.442.36004 Boehringer Ingelheim Investigational Site

Komárom, Hungary

Location

205.442.36006 Boehringer Ingelheim Investigational Site

Pécs, Hungary

Location

205.442.36001 Boehringer Ingelheim Investigational Site

Szarvas, Hungary

Location

205.442.36005 Boehringer Ingelheim Investigational Site

Százhalombatta, Hungary

Location

205.442.91011 Boehringer Ingelheim Investigational Site

Ahmedabad, India

Location

205.442.91005 Boehringer Ingelheim Investigational Site

Bangalore, India

Location

205.442.91009 Boehringer Ingelheim Investigational Site

Banglore, India

Location

205.442.91002 Boehringer Ingelheim Investigational Site

Coimbatore, India

Location

205.442.91003 Boehringer Ingelheim Investigational Site

Coimbatore, India

Location

205.442.91004 Boehringer Ingelheim Investigational Site

Coimbatore, India

Location

205.442.91008 Boehringer Ingelheim Investigational Site

Hyderabad, India

Location

205.442.91007 Boehringer Ingelheim Investigational Site

Jaipur, India

Location

205.442.91001 Boehringer Ingelheim Investigational Site

Nagpur, India

Location

205.442.91006 Boehringer Ingelheim Investigational Site

Pune, India

Location

205.442.39007 Boehringer Ingelheim Investigational Site

Acquaviva Delle Fonti (BA), Italy

Location

205.442.39006 Boehringer Ingelheim Investigational Site

Cagliari, Italy

Location

205.442.39003 Boehringer Ingelheim Investigational Site

Chieti, Italy

Location

205.442.39001 Boehringer Ingelheim Investigational Site

Pisa, Italy

Location

205.442.37101 Boehringer Ingelheim Investigational Site

Baldone, Latvia

Location

205.442.37103 Boehringer Ingelheim Investigational Site

Daugavpils, Latvia

Location

205.442.37104 Boehringer Ingelheim Investigational Site

Daugavpils, Latvia

Location

205.442.37102 Boehringer Ingelheim Investigational Site

Talsi, Latvia

Location

205.442.48003 Boehringer Ingelheim Investigational Site

Giżycko, Poland

Location

205.442.48002 Boehringer Ingelheim Investigational Site

Gorzów Wielkopolski, Poland

Location

205.442.48005 Boehringer Ingelheim Investigational Site

Krakow, Poland

Location

205.442.48004 Boehringer Ingelheim Investigational Site

Ostrow Wielkopolska, Poland

Location

205.442.48001 Boehringer Ingelheim Investigational Site

Poznan, Poland

Location

205.442.42105 Boehringer Ingelheim Investigational Site

Bardejov, Slovakia

Location

205.442.42107 Boehringer Ingelheim Investigational Site

Humenné, Slovakia

Location

205.442.42104 Boehringer Ingelheim Investigational Site

Košice, Slovakia

Location

205.442.42102 Boehringer Ingelheim Investigational Site

Nitra, Slovakia

Location

205.442.42101 Boehringer Ingelheim Investigational Site

Nové Zámky, Slovakia

Location

205.442.42108 Boehringer Ingelheim Investigational Site

Poprad, Slovakia

Location

205.442.42106 Boehringer Ingelheim Investigational Site

Spišská Nová Ves, Slovakia

Location

205.442.42103 Boehringer Ingelheim Investigational Site

Topoľčany, Slovakia

Location

205.442.82006 Boehringer Ingelheim Investigational Site

Cheongju-si, South Korea

Location

205.442.82002 Boehringer Ingelheim Investigational Site

Gangwon-do, South Korea

Location

205.442.82001 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

205.442.82003 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

205.442.82004 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

205.442.82005 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

Related Publications (4)

• 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

• Halpin DMG, Hamelmann EH, Frith PA, Moroni-Zentgraf PM, van Hecke B, Unseld A, Kerstjens HAM, Szefler SJ. Comparative Responses in Lung Function Measurements with Tiotropium in Adolescents and Adults, and Across Asthma Severities: A Post Hoc Analysis. Pulm Ther. 2020 Jun;6(1):131-140. doi: 10.1007/s41030-020-00113-w. Epub 2020 Mar 16.

  PMID: 32180164 DERIVED

• Halpin DMG, Meltzer EO, Pisternick-Ruf W, Moroni-Zentgraf P, Engel M, Zaremba-Pechmann L, Casale T, FitzGerald JM. Peak expiratory flow as an endpoint for clinical trials in asthma: a comparison with FEV1. Respir Res. 2019 Jul 18;20(1):159. doi: 10.1186/s12931-019-1119-6.

  PMID: 31319851 DERIVED

• Paggiaro P, Halpin DM, Buhl R, Engel M, Zubek VB, Blahova Z, Moroni-Zentgraf P, Pizzichini E. The Effect of Tiotropium in Symptomatic Asthma Despite Low- to Medium-Dose Inhaled Corticosteroids: A Randomized Controlled Trial. J Allergy Clin Immunol Pract. 2016 Jan-Feb;4(1):104-13.e2. doi: 10.1016/j.jaip.2015.08.017. Epub 2015 Nov 7.

  PMID: 26563670 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Tiotropium Bromide

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

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• 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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2011
• First Posted: March 16, 2011
• Study Start: March 1, 2011
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: April 15, 2015
• Results First Posted: July 31, 2013

Record last verified: 2015-03

Locations

CR (4); GU (5); ES (3); IN (10); PL (5); KR (6); HU (7); AU (3); AR (3); LA (4); SL (8); IT (4)