Efficacy and Safety of 2 Doses of Tiotropium Respimat® Compared to Placebo in Children With Severe Persistent Asthma

NCT01634152 | Completed Phase 3 Results

• 2 other identifiers: 205.4462011-001777-43
• Study Type: interventional
• Target: 401
• Locations: 17 countries
• Sites: 94

Brief Summary

The overall purpose of the trial is to evaluate efficacy and safety of tiotropium inhalation solution (2.5 mcg and 5 mcg) delivered via Respimat® inhaler once daily in the evening over 12 weeks, compared to placebo, as add-on controller therapy on top of usual care in children (6 to 11 years old) with severe persistent asthma.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

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

  Change from baseline in peak forced expiratory volume in 1 second within the first 3 hours post dosing (FEV1 peak(0-3h)) measured at week 12. Measured values presented are actually adjusted means.

  Baseline and 12 weeks

Secondary Outcomes (24)

• Trough FEV1 Change From Baseline

  Baseline and 12 weeks

• FVC Peak(0-3h) Change From Baseline

  Baseline and 12 weeks

• Trough FVC Change From Baseline

  Baseline and 12 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 12 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 12 weeks

Study Arms (3)

Placebo QD

PLACEBO COMPARATOR

Drug: Placebo

Tiotropium low dose QD

EXPERIMENTAL

Drug: Tiotropium low dose mcg

Tiotropium medium dose QD

EXPERIMENTAL

Drug: Tiotropium high dose

Interventions

Placebo DRUG

2 actuations once daily in the evening

Placebo QD

Tiotropium low dose mcg DRUG

2 actuations once daily in the evening

Tiotropium low dose QD

Tiotropium high dose DRUG

2 actuations once daily in the evening

Tiotropium medium dose QD

Eligibility Criteria

• Age: 6 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• All patients' parent(s) (or legal guardian) must sign and date an informed consent prior to participation in the trial. In addition, an informed assent suitable for this age group has to be obtained from patients. A separate informed consent/assent is required for pharmacogenomic sampling.
• Male or female patients between 6 and 11 years of age.
• All patients must have at least a 6-month history of asthma.
• All patients must have been on maintenance treatment with an inhaled corticosteroid either at stable high dose in combination with another controller medication, OR at stable medium dose in combination with two other controller medications, for at least 4 weeks before Visit 1.
• All patients must be symptomatic (partly controlled) at Visit 1 and prior to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ-IA) mean score \>= 1.5.
• All patients must have a pre-bronchodilator forced expiratory volume in one second (FEV1) \>= 60% and \<= 90% of predicted normal at Visit 1.
• Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator, considered as 100%) as compared to Visit 2 (pre-dose) must be within ± 30%.
• All patients must confirm the diagnosis of asthma by bronchodilator reversibility at Visit 1, resulting in an increase in FEV1 of \>= 12% 15 to 30 minutes after 200 mcg salbutamol/albuterol.
• 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 electronic diary/peak flow meter (diary compliance of at least 80% is required).

You may not qualify if:

• Patients with a significant disease other than asthma.
• Patients with a clinically relevant abnormal haematology or blood chemistry at screening.
• Patients with a history of congenital or acquired heart disease, or patients who 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 a malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.
• Patients with known active tuberculosis.
• 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 six weeks prior to Visit 1.
• Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the inhalation solution used with the Respimat inhaler.
• Pregnant or nursing female patients, including postmenarchal girls with a positive urine pregnancy test at Visit 1.
• Postmenarchal girls of child-bearing potential not using a highly effective method of birth control.
• Patients who have been treated with systemic corticosteroids within four weeks prior to Visit 1.
• Patients who have been treated with systemic beta-adrenergics within four weeks prior to Visit 1.
• Patients who have been treated with oral beta-blocker medication within four weeks prior to Visit 1 and/or during the screening period.
• Patients who have been treated with inhaled long-acting anticholinergics or systemic anticholinergic treatment within four weeks prior to Visit 1 and/or during the screening period, or who have been treated with inhaled short-acting anticholinergics within two weeks prior to Visit 1.

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Pfizer: collaborator

Study Sites (94)

205.446.01014 Boehringer Ingelheim Investigational Site

Rolling Hills Estates, California, United States

Location

205.446.01011 Boehringer Ingelheim Investigational Site

Denver, Colorado, United States

Location

205.446.01003 Boehringer Ingelheim Investigational Site

North Dartmouth, Massachusetts, United States

Location

205.446.01009 Boehringer Ingelheim Investigational Site

Columbia, Missouri, United States

Location

205.446.01005 Boehringer Ingelheim Investigational Site

Cincinnati, Ohio, United States

Location

205.446.01010 Boehringer Ingelheim Investigational Site

Oklahoma City, Oklahoma, United States

Location

205.446.01004 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

Location

205.446.01002 Boehringer Ingelheim Investigational Site

North Charleston, South Carolina, United States

Location

205.446.01012 Boehringer Ingelheim Investigational Site

Arlington, Texas, United States

Location

205.446.01013 Boehringer Ingelheim Investigational Site

San Antonio, Texas, United States

Location

205.446.54006 Boehringer Ingelheim Investigational Site

Buenos Aires, Argentina

Location

205.446.54002 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

205.446.54003 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

205.446.54008 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

205.446.54005 Boehringer Ingelheim Investigational Site

Mar del Plata, Argentina

Location

205.446.54004 Boehringer Ingelheim Investigational Site

Mendoza, Argentina

Location

205.446.54007 Boehringer Ingelheim Investigational Site

San Miguel de Tucumán, Argentina

Location

205.446.61003 Boehringer Ingelheim Investigational Site

Herston, Queensland, Australia

Location

205.446.61001 Boehringer Ingelheim Investigational Site

Perth, Western Australia, Australia

Location

205.446.32004 Boehringer Ingelheim Investigational Site

Antwerp, Belgium

Location

205.446.32005 Boehringer Ingelheim Investigational Site

Bruges, Belgium

Location

205.446.32006 Boehringer Ingelheim Investigational Site

Namur, Belgium

Location

205.446.55001 Boehringer Ingelheim Investigational Site

Curitiba, Brazil

Location

205.446.55007 Boehringer Ingelheim Investigational Site

Goiânia, Brazil

Location

205.446.55006 Boehringer Ingelheim Investigational Site

Porto Alegre, Brazil

Location

205.446.55002 Boehringer Ingelheim Investigational Site

São Paulo, Brazil

Location

205.446.55003 Boehringer Ingelheim Investigational Site

São Paulo, Brazil

Location

205.446.55004 Boehringer Ingelheim Investigational Site

São Paulo, Brazil

Location

205.446.55005 Boehringer Ingelheim Investigational Site

São Paulo, Brazil

Location

205.446.02003 Boehringer Ingelheim Investigational Site

London, Ontario, Canada

Location

205.446.02001 Boehringer Ingelheim Investigational Site

Sherbrooke, Quebec, Canada

Location

205.446.42005 Boehringer Ingelheim Investigational Site

Jablonec nad Nisou, Czechia

Location

205.446.42001 Boehringer Ingelheim Investigational Site

Jihlava, Czechia

Location

205.446.42002 Boehringer Ingelheim Investigational Site

Prague, Czechia

Location

205.446.42004 Boehringer Ingelheim Investigational Site

Prague, Czechia

Location

205.446.49012 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

205.446.49015 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

205.446.49001 Boehringer Ingelheim Investigational Site

Bochum, Germany

Location

205.446.49007 Boehringer Ingelheim Investigational Site

Dresden, Germany

Location

205.446.49003 Boehringer Ingelheim Investigational Site

Frankfurt, Germany

Location

205.446.49009 Boehringer Ingelheim Investigational Site

Koblenz, Germany

Location

205.446.49014 Boehringer Ingelheim Investigational Site

Marburg, Germany

Location

205.446.49011 Boehringer Ingelheim Investigational Site

Mönchengladbach, Germany

Location

205.446.50201 Boehringer Ingelheim Investigational Site

Guatemala City, Guatemala

Location

205.446.50202 Boehringer Ingelheim Investigational Site

Guatemala City, Guatemala

Location

205.446.50203 Boehringer Ingelheim Investigational Site

Guatemala City, Guatemala

Location

205.446.50204 Boehringer Ingelheim Investigational Site

Guatemala City, Guatemala

Location

205.446.36002 Boehringer Ingelheim Investigational Site

Ajka, Hungary

Location

205.446.36001 Boehringer Ingelheim Investigational Site

Budapest, Hungary

Location

205.446.36003 Boehringer Ingelheim Investigational Site

Nagyatád, Hungary

Location

205.446.36004 Boehringer Ingelheim Investigational Site

Szeged, Hungary

Location

205.446.37105 Boehringer Ingelheim Investigational Site

Baldone, Latvia

Location

205.446.37104 Boehringer Ingelheim Investigational Site

Balvi, Latvia

Location

205.446.37108 Boehringer Ingelheim Investigational Site

Daugavpils, Latvia

Location

205.446.37107 Boehringer Ingelheim Investigational Site

Jēkabpils, Latvia

Location

205.446.37101 Boehringer Ingelheim Investigational Site

Ogre, Latvia

Location

205.446.37106 Boehringer Ingelheim Investigational Site

Rēzekne, Latvia

Location

205.446.37102 Boehringer Ingelheim Investigational Site

Riga, Latvia

Location

205.446.37103 Boehringer Ingelheim Investigational Site

Riga, Latvia

Location

205.446.37004 Boehringer Ingelheim Investigational Site

Šiauliai, Lithuania

Location

205.446.37003 Boehringer Ingelheim Investigational Site

Tauragė, Lithuania

Location

205.446.37002 Boehringer Ingelheim Investigational Site

Utena, Lithuania

Location

205.446.37001 Boehringer Ingelheim Investigational Site

Vilnius, Lithuania

Location

205.446.48004 Boehringer Ingelheim Investigational Site

Bialystok, Poland

Location

205.446.48002 Boehringer Ingelheim Investigational Site

Lodz, Poland

Location

205.446.48001 Boehringer Ingelheim Investigational Site

Lublin, Poland

Location

205.446.48003 Boehringer Ingelheim Investigational Site

Tarnów, Poland

Location

205.446.40002 Boehringer Ingelheim Investigational Site

Bucharest, Romania

Location

205.446.70002 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.446.70005 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.446.70007 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.446.70011 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.446.70012 Boehringer Ingelheim Investigational Site

Novosibirsk, Russia

Location

205.446.70001 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.446.70003 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.446.70004 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.446.70010 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.446.70009 Boehringer Ingelheim Investigational Site

Yaroslavl, Russia

Location

205.446.42101 Boehringer Ingelheim Investigational Site

Košice, Slovakia

Location

205.446.42103 Boehringer Ingelheim Investigational Site

Prešov, Slovakia

Location

205.446.42102 Boehringer Ingelheim Investigational Site

Spišská Nová Ves, Slovakia

Location

205.446.38013 Boehringer Ingelheim Investigational Site

Chernivtsi, Ukraine

Location

205.446.38002 Boehringer Ingelheim Investigational Site

Dnipropetrovsk, Ukraine

Location

205.446.38003 Boehringer Ingelheim Investigational Site

Dnipropetrovsk, Ukraine

Location

205.446.38005 Boehringer Ingelheim Investigational Site

Donetsk, Ukraine

Location

205.446.38012 Boehringer Ingelheim Investigational Site

Donetsk, Ukraine

Location

205.446.38009 Boehringer Ingelheim Investigational Site

Kharkiv, Ukraine

Location

205.446.38004 Boehringer Ingelheim Investigational Site

Kiev, Ukraine

Location

205.446.38006 Boehringer Ingelheim Investigational Site

Kryvyi Rih, Ukraine

Location

205.446.38001 Boehringer Ingelheim Investigational Site

Lviv, Ukraine

Location

205.446.38014 Boehringer Ingelheim Investigational Site

Odesa, Ukraine

Location

205.446.38010 Boehringer Ingelheim Investigational Site

Vinnytsia, Ukraine

Location

205.446.38011 Boehringer Ingelheim Investigational Site

Zaporizhya, Ukraine

Location

205.446.38008 Boehringer Ingelheim Investigational Site

Zaporizhzhya, Ukraine

Location

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

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: July 3, 2012
• First Posted: July 6, 2012
• Study Start: July 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: January 29, 2016
• Results First Posted: December 21, 2015

Record last verified: 2015-12

Locations

BE (3); BR (7); US (10); DE (8); LA (8); RU (10); HU (4); LI (4); CZ (4); UA (13); PL (4); AU (2); SL (3); RO (1); GU (4); AR (7); CA (2)