Efficacy and Safety of 2 Doses of Tiotropium Via Respimat Compared to Placebo in Adolescents With Moderate Persistent Asthma

NCT01257230 | Completed Phase 3 Results

• 2 other identifiers: 205.4442010-021093-11
• Study Type: interventional
• Target: 398
• Locations: 12 countries
• Sites: 66

Brief Summary

The aim of the study is to evaluate efficacy and safety of a 48-week treatment with two doses of tiotropium bromide compared to placebo in adolescent patients with moderate persistent asthma. Efficacy and safety will be assessed by measuring lung function parameters and evaluating the effects on asthma exacerbations, on Quality of life, on health care resource utilisation an on the number of adverse events.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• FEV1 peak0-3 Change From Baseline

  Change from baseline in peak Forced expiratory volume in 1 second within the first 3 hours post dosing (FEV1 peak0-3) measured at week 24. Note, the measured values presented are actually adjusted means.

  Baseline and 24 weeks

Secondary Outcomes (15)

• Trough FEV1 Change From Baseline

  Baseline and 24 weeks

• FVC peak0-3 Change From Baseline

  Baseline and 24 weeks

• Trough FVC Change From Baseline

  Baseline and 24 weeks

• FEV1 AUC (0-3h) Change From Baseline

  Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks

• FVC AUC (0-3h) Change From Baseline

  Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks

Study Arms (3)

placebo

PLACEBO COMPARATOR

once daily, delivered with Respimat inhaler

Drug: placebo Respimat

tiotropium low dose

EXPERIMENTAL

once daily, delivered with Respimat inhaler

Drug: tiotropium Respimat low dose

tiotropium high dose

EXPERIMENTAL

once daily, delivered with Respimat inhaler

Drug: tiotropium Respimat high dose

Interventions

tiotropium Respimat low dose DRUG

IMP

tiotropium low dose

placebo Respimat DRUG

placebo representing comparator

placebo

tiotropium Respimat high dose DRUG

IMP

tiotropium high dose

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• All patients and their parents (or legally accepted caregiver) must sign and date an informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial.
• Male or female patients between 12 and 17 years of age.
• All patients must have at least a 3 months history of asthma at the time of enrolment into the trial. The diagnosis of asthma has to be confirmed at visit 1 with a bronchodilator reversibility test.
• All patients must have been on maintenance treatment with inhaled corticosteroids at a stable medium dose for at least 4 weeks before Visit 1.
• All patients must be symptomatic (partly controlled) at Visit 1 (screening) and at randomisation defined by an Asthma Control Questionnaire (ACQ) mean score of more than or equal to 1.5.
• All patients must have a pre-bronchodilator FEV1 more than or equal to 60% and less than or equal to 90% of predicted normal at Visit 1. Variation of absolute FEV1 values of Visit 1 as compared to Visit 2 must be within ± 30%.
• All patients must have an increase in FEV1 of equal or above 12% and 200 mL after 400 µg salbutamol (albuterol) at Visit 1. If patients in the lower age range (e.g., 12 to 14 year olds) exhibit a very small total lung volume, positive reversibility testing might be based solely on the relative (12%) post-bronchodilator response.
• All patients should be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment.
• Patients should be able to use the Respimat® inhaler correctly.
• Patients must be able to perform all trial related procedures including technically acceptable spirometric manoeuvres.

You may not qualify if:

• Patients with a significant disease other than asthma.
• Patients with clinically relevant abnormal screening haematology or blood chemistry
• Patients with a history of congenital or acquired heart disease, and/or have been hospitalised for cardiac syncope or 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 malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.
• Patients with known active tuberculosis.
• Patients with significant alcohol or drug abuse within the past two years.
• Patients who have undergone thoracotomy with pulmonary resection.
• Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit 1).
• Patients with known hypersensitivity to anticholinergic drugs, Benzalkonium chloride (BAC), Ethylenediaminetetraacetic acis (EDTA) or any other components of the tiotropium inhalation solution.
• Pregnant or nursing adolescent female patients
• Sexually active female patients of child-bearing potential not using a highly effective method of birth control.
• Patients who have taken an investigational drug within 4 weeks prior to Visit 1.
• Patients who have been treated with long-acting anticholinergics (e.g. tiotropium -Spiriva) within four weeks prior to screening (Visit 1).
• Patients who are unable to comply with pulmonary medication restrictions prior to randomisation.

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Pfizer: collaborator

Study Sites (66)

205.444.01004 Boehringer Ingelheim Investigational Site

Plymouth, Minnesota, United States

Location

205.444.01005 Boehringer Ingelheim Investigational Site

Columbia, Missouri, United States

Location

205.444.01001 Boehringer Ingelheim Investigational Site

Cincinnati, Ohio, United States

Location

205.444.01014 Boehringer Ingelheim Investigational Site

Oklahoma City, Oklahoma, United States

Location

205.444.01002 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

Location

205.444.01012 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

Location

205.444.01013 Boehringer Ingelheim Investigational Site

El Paso, Texas, United States

Location

205.444.01003 Boehringer Ingelheim Investigational Site

South Burlington, Vermont, United States

Location

205.444.56002 Boehringer Ingelheim Investigational Site

Santiago, Chile

Location

205.444.56001 Boehringer Ingelheim Investigational Site

Viña del Mar, Chile

Location

205.444.56003 Boehringer Ingelheim Investigational Site

Viña del Mar, Chile

Location

205.444.49007 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

205.444.49008 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

205.444.49001 Boehringer Ingelheim Investigational Site

Bochum, Germany

Location

205.444.49003 Boehringer Ingelheim Investigational Site

Ettenheim, Germany

Location

205.444.49006 Boehringer Ingelheim Investigational Site

Koblenz, Germany

Location

205.444.49005 Boehringer Ingelheim Investigational Site

Rosenheim, Germany

Location

205.444.36007 Boehringer Ingelheim Investigational Site

Ajka, Hungary

Location

205.444.36005 Boehringer Ingelheim Investigational Site

Budapest, Hungary

Location

205.444.36008 Boehringer Ingelheim Investigational Site

Budapest, Hungary

Location

205.444.36006 Boehringer Ingelheim Investigational Site

Kaposvár, Hungary

Location

205.444.36001 Boehringer Ingelheim Investigational Site

Miskolc, Hungary

Location

205.444.36002 Boehringer Ingelheim Investigational Site

Mosdós, Hungary

Location

205.444.36003 Boehringer Ingelheim Investigational Site

Szeged, Hungary

Location

205.444.36004 Boehringer Ingelheim Investigational Site

Szigetbecse, Hungary

Location

205.444.39001 Boehringer Ingelheim Investigational Site

Ancona, Italy

Location

205.444.39003 Boehringer Ingelheim Investigational Site

Bolzano, Italy

Location

205.444.39002 Boehringer Ingelheim Investigational Site

Verona, Italy

Location

205.444.37101 Boehringer Ingelheim Investigational Site

Baldone, Latvia

Location

205.444.37107 Boehringer Ingelheim Investigational Site

Balvi, Latvia

Location

205.444.37102 Boehringer Ingelheim Investigational Site

Ogre, Latvia

Location

205.444.37105 Boehringer Ingelheim Investigational Site

Rēzekne, Latvia

Location

205.444.37106 Boehringer Ingelheim Investigational Site

Riga, Latvia

Location

205.444.37103 Boehringer Ingelheim Investigational Site

Talsi, Latvia

Location

205.444.37104 Boehringer Ingelheim Investigational Site

Tukums, Latvia

Location

205.444.52002 Boehringer Ingelheim Investigational Site

Guadalajara, Mexico

Location

205.444.52001 Boehringer Ingelheim Investigational Site

Hermosillo, Mexico

Location

205.444.52003 Boehringer Ingelheim Investigational Site

Monterrey, Mexico

Location

205.444.70003 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.444.70002 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.444.70004 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.444.70005 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.444.70006 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.444.70001 Boehringer Ingelheim Investigational Site

Yaroslavl, Russia

Location

205.444.42104 Boehringer Ingelheim Investigational Site

Košice, Slovakia

Location

205.444.42106 Boehringer Ingelheim Investigational Site

Martin, Slovakia

Location

205.444.42101 Boehringer Ingelheim Investigational Site

Nitra, Slovakia

Location

205.444.42105 Boehringer Ingelheim Investigational Site

Rožňava, Slovakia

Location

205.444.82003 Boehringer Ingelheim Investigational Site

Guri-si, South Korea

Location

205.444.82006 Boehringer Ingelheim Investigational Site

Incheon, South Korea

Location

205.444.82001 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

205.444.82004 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

205.444.34007 Boehringer Ingelheim Investigational Site

Esplugues Del Llobregat, Spain

Location

205.444.34001 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

205.444.34004 Boehringer Ingelheim Investigational Site

Majadahonda (Madrid), Spain

Location

205.444.34005 Boehringer Ingelheim Investigational Site

Marbella, Spain

Location

205.444.34006 Boehringer Ingelheim Investigational Site

Sabdadell, Spain

Location

205.444.34008 Boehringer Ingelheim Investigational Site

Valencia, Spain

Location

205.444.38008 Boehringer Ingelheim Investigational Site

Dnipropetrovsk, Ukraine

Location

205.444.38002 Boehringer Ingelheim Investigational Site

Donetsk, Ukraine

Location

205.444.38005 Boehringer Ingelheim Investigational Site

Kharkiv, Ukraine

Location

205.444.38003 Boehringer Ingelheim Investigational Site

Kiev, Ukraine

Location

205.444.38004 Boehringer Ingelheim Investigational Site

Kiev, Ukraine

Location

205.444.38001 Boehringer Ingelheim Investigational Site

Lviv, Ukraine

Location

205.444.38010 Boehringer Ingelheim Investigational Site

Zaporizhya, Ukraine

Location

205.444.38009 Boehringer Ingelheim Investigational Site

Zaporizhzhya, Ukraine

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

• Hamelmann E, Bateman ED, Vogelberg C, Szefler SJ, Vandewalker M, Moroni-Zentgraf P, Avis M, Unseld A, Engel M, Boner AL. Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial. J Allergy Clin Immunol. 2016 Aug;138(2):441-450.e8. doi: 10.1016/j.jaci.2016.01.011. Epub 2016 Mar 5.

  PMID: 26960245 DERIVED

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

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

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: December 6, 2010
• First Posted: December 9, 2010
• Study Start: December 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: September 5, 2014
• Results First Posted: August 8, 2014

Record last verified: 2014-08

Locations

IT (3); RU (6); DE (6); KR (4); ES (6); US (8); UA (8); CL (3); ME (3); SL (4); LA (7); HU (8)