Clinical trial NCT01634152: Efficacy and Safety of 2 Doses of Tiotropium Respimat® Compared to Placebo in Children With Severe Persistent Asthma
Official title: A Randomised, Double-blind, Placebo-controlled, Parallel-group Trial 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 as add-on Controller Therapy on Top of Usual Care in Children (6 to 11 Years Old) With Severe Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2012-07-06
Enrollment: 401
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion criteria:

Inclusion criteria are:

1. 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.
2. Male or female patients between 6 and 11 years of age.
3. All patients must have at least a 6-month history of asthma.
4. 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.
5. 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.
6. All patients must have a pre-bronchodilator forced expiratory volume in one second (FEV1) \>= 60% and \<= 90% of predicted normal at Visit 1.
7. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator, considered as 100%) as compared to Visit 2 (pre-dose) must be within ± 30%.
8. 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.
9. Patients must be able to use the Respimat inhaler correctly.
10. 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).

Exclusion criteria:

Exclusion criteria are:

1. Patients with a significant disease other than asthma.
2. Patients with a clinically relevant abnormal haematology or blood chemistry at screening.
3. 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.
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 a malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.
6. Patients with known active tuberculosis.
7. Patients who have undergone thoracotomy with pulmonary resection.
8. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the six weeks prior to Visit 1.
9. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the inhalation solution used with the Respimat inhaler.
10. Pregnant or nursing female patients, including postmenarchal girls with a positive urine pregnancy test at Visit 1.
11. Postmenarchal girls of child-bearing potential not using a highly effective method of birth control.
12. Patients who have been treated with systemic corticosteroids within four weeks prior to Visit 1.
13. Patients who have been treated with systemic beta-adrenergics within four weeks prior to Visit 1.
14. Patients who have been treated with oral beta-blocker medication within four weeks prior to Visit 1 and/or during the screening period.
15. 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.
16. Patients who have been treated with short-acting theophylline preparations within two weeks prior to Visit 1.
17. Patients who have been treated with non-approved and according to international guidelines not recommended experimental drugs for routine asthma therapy within four weeks prior to Visit 1 and/or during the screening period.
18. Patients who have taken an investigational drug within six half lives according to the investigator's information, or four weeks (whichever is greater) prior to Visit 1 and/or during the screening period.
19. Patients who have previously been randomised in this trial or are currently participating in another trial.
20. Patients with any acute asthma exacerbation or respiratory tract infection in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2. In case of an asthma deterioration occurring in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2, the visit must be postponed.
21. Patients requiring six or more puffs of rescue medication per day on more than two consecutive days in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2. In case of an asthma deterioration occurring in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2, the visit must be postponed.
22. Patients who are unable to comply with medication restrictions prior to Visit 1 and/or prior to Visit 2.
23. Patients with a known narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated.
24. Patients with moderate to severe renal impairment, as defined by a creatinine clearance \<50 mL/min/1.73 m2 BSA, as tiotropium is a predominantly renally excreted drug.

Primary outcomes:
measure: FEV1 Peak(0-3h) Change From Baseline
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Trough FEV1 Change From Baseline
timeFrame: Baseline and 12 weeks
measure: FVC Peak(0-3h) Change From Baseline
timeFrame: Baseline and 12 weeks
measure: Trough FVC Change From Baseline
timeFrame: Baseline and 12 weeks
measure: FEV1 AUC (0-3h) Change From Baseline
timeFrame: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks
measure: FVC AUC (0-3h) Change From Baseline
timeFrame: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks
measure: FEV1 Change From Baseline at Each Individual Timepoint
timeFrame: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks
measure: FVC Change From Baseline at Each Individual Timepoint
timeFrame: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks
measure: Control of Asthma as Assessed by ACQ-IA Total Score
timeFrame: Baseline and 12 weeks
measure: ACQ-IA Total Score Responders
timeFrame: 12 weeks
measure: Use of PRN Rescue Medication Per Day
timeFrame: Baseline and 12 weeks
measure: Use of PRN Rescue Medication During the Daytime
timeFrame: Baseline and 12 weeks
measure: Use of PRN Rescue Medication During the Night-time
timeFrame: Baseline and 12 weeks
measure: Peak Expiratory Flow (PEF) a.m. Change From Baseline
timeFrame: Baseline and 12 weeks
measure: Peak Expiratory Flow (PEF) p.m. Change From Baseline
timeFrame: Baseline and 12 weeks
measure: Peak Expiratory Flow (PEF) Variability Change From Baseline
timeFrame: Baseline and 12 weeks
measure: FEV1 a.m. Change From Baseline
timeFrame: Baseline and 12 weeks
measure: FEV1 p.m. Change From Baseline
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Nighttime Awakenings
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Morning Asthma Symptoms
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Daytime Asthma Symptoms
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Daytime Activity Limitations
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Daytime Experiences of Shortness of Breath
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Daytime Experiences of Wheeze or Cough
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Asthma Symptom-free Days
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Rolling Hills Estates
country: United States
facility: 205.446.01014 Boehringer Ingelheim Investigational Site
state: California
city: Denver
country: United States
facility: 205.446.01011 Boehringer Ingelheim Investigational Site
state: Colorado
city: North Dartmouth
country: United States
facility: 205.446.01003 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Columbia
country: United States
facility: 205.446.01009 Boehringer Ingelheim Investigational Site
state: Missouri
city: Cincinnati
country: United States
facility: 205.446.01005 Boehringer Ingelheim Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: 205.446.01010 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Charleston
country: United States
facility: 205.446.01004 Boehringer Ingelheim Investigational Site
state: South Carolina
city: North Charleston
country: United States
facility: 205.446.01002 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Arlington
country: United States
facility: 205.446.01012 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 205.446.01013 Boehringer Ingelheim Investigational Site
state: Texas
city: Buenos Aires
country: Argentina
facility: 205.446.54006 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 205.446.54002 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 205.446.54003 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 205.446.54008 Boehringer Ingelheim Investigational Site
city: Mar del Plata
country: Argentina
facility: 205.446.54005 Boehringer Ingelheim Investigational Site
city: Mendoza
country: Argentina
facility: 205.446.54004 Boehringer Ingelheim Investigational Site
city: San Miguel de Tucuman
country: Argentina
facility: 205.446.54007 Boehringer Ingelheim Investigational Site
city: Herston
country: Australia
facility: 205.446.61003 Boehringer Ingelheim Investigational Site
state: Queensland
city: Perth
country: Australia
facility: 205.446.61001 Boehringer Ingelheim Investigational Site
state: Western Australia
city: Antwerpen
country: Belgium
facility: 205.446.32004 Boehringer Ingelheim Investigational Site
city: Brugge
country: Belgium
facility: 205.446.32005 Boehringer Ingelheim Investigational Site
city: Namur
country: Belgium
facility: 205.446.32006 Boehringer Ingelheim Investigational Site
city: Curitiba
country: Brazil
facility: 205.446.55001 Boehringer Ingelheim Investigational Site
city: Goiânia
country: Brazil
facility: 205.446.55007 Boehringer Ingelheim Investigational Site
city: Porto Alegre
country: Brazil
facility: 205.446.55006 Boehringer Ingelheim Investigational Site
city: Sao Paulo
country: Brazil
facility: 205.446.55002 Boehringer Ingelheim Investigational Site
city: Sao Paulo
country: Brazil
facility: 205.446.55003 Boehringer Ingelheim Investigational Site
city: Sao Paulo
country: Brazil
facility: 205.446.55004 Boehringer Ingelheim Investigational Site
city: Sao Paulo
country: Brazil
facility: 205.446.55005 Boehringer Ingelheim Investigational Site
city: London
country: Canada
facility: 205.446.02003 Boehringer Ingelheim Investigational Site
state: Ontario
city: Sherbrooke
country: Canada
facility: 205.446.02001 Boehringer Ingelheim Investigational Site
state: Quebec
city: Jablonec nad Nisou
country: Czech Republic
facility: 205.446.42005 Boehringer Ingelheim Investigational Site
city: Jihlava
country: Czech Republic
facility: 205.446.42001 Boehringer Ingelheim Investigational Site
city: Prague
country: Czech Republic
facility: 205.446.42002 Boehringer Ingelheim Investigational Site
city: Prague
country: Czech Republic
facility: 205.446.42004 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 205.446.49012 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 205.446.49015 Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: 205.446.49001 Boehringer Ingelheim Investigational Site
city: Dresden
country: Germany
facility: 205.446.49007 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 205.446.49003 Boehringer Ingelheim Investigational Site
city: Koblenz
country: Germany
facility: 205.446.49009 Boehringer Ingelheim Investigational Site
city: Marburg
country: Germany
facility: 205.446.49014 Boehringer Ingelheim Investigational Site
city: Mönchengladbach
country: Germany
facility: 205.446.49011 Boehringer Ingelheim Investigational Site
city: Guatemala
country: Guatemala
facility: 205.446.50201 Boehringer Ingelheim Investigational Site
city: Guatemala
country: Guatemala
facility: 205.446.50202 Boehringer Ingelheim Investigational Site
city: Guatemala
country: Guatemala
facility: 205.446.50203 Boehringer Ingelheim Investigational Site
city: Guatemala
country: Guatemala
facility: 205.446.50204 Boehringer Ingelheim Investigational Site
city: Ajka
country: Hungary
facility: 205.446.36002 Boehringer Ingelheim Investigational Site
city: Budapest
country: Hungary
facility: 205.446.36001 Boehringer Ingelheim Investigational Site
city: Nagyatad
country: Hungary
facility: 205.446.36003 Boehringer Ingelheim Investigational Site
city: Szeged
country: Hungary
facility: 205.446.36004 Boehringer Ingelheim Investigational Site
city: Baldone
country: Latvia
facility: 205.446.37105 Boehringer Ingelheim Investigational Site
city: Balvi
country: Latvia
facility: 205.446.37104 Boehringer Ingelheim Investigational Site
city: Daugavpils
country: Latvia
facility: 205.446.37108 Boehringer Ingelheim Investigational Site
city: Jekabpils
country: Latvia
facility: 205.446.37107 Boehringer Ingelheim Investigational Site
city: Ogre
country: Latvia
facility: 205.446.37101 Boehringer Ingelheim Investigational Site
city: Rezekne
country: Latvia
facility: 205.446.37106 Boehringer Ingelheim Investigational Site
city: Riga
country: Latvia
facility: 205.446.37102 Boehringer Ingelheim Investigational Site
city: Riga
country: Latvia
facility: 205.446.37103 Boehringer Ingelheim Investigational Site
city: Siauliai
country: Lithuania
facility: 205.446.37004 Boehringer Ingelheim Investigational Site
city: Taurage
country: Lithuania
facility: 205.446.37003 Boehringer Ingelheim Investigational Site
city: Utena
country: Lithuania
facility: 205.446.37002 Boehringer Ingelheim Investigational Site
city: Vilnius
country: Lithuania
facility: 205.446.37001 Boehringer Ingelheim Investigational Site
city: Bialystok
country: Poland
facility: 205.446.48004 Boehringer Ingelheim Investigational Site
city: Lodz
country: Poland
facility: 205.446.48002 Boehringer Ingelheim Investigational Site
city: Lublin
country: Poland
facility: 205.446.48001 Boehringer Ingelheim Investigational Site
city: Tarnow
country: Poland
facility: 205.446.48003 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 205.446.40002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 205.446.70002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 205.446.70005 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 205.446.70007 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 205.446.70011 Boehringer Ingelheim Investigational Site
city: Novosibirsk
country: Russian Federation
facility: 205.446.70012 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 205.446.70001 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 205.446.70003 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 205.446.70004 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 205.446.70010 Boehringer Ingelheim Investigational Site
city: Yaroslavl
country: Russian Federation
facility: 205.446.70009 Boehringer Ingelheim Investigational Site
city: Kosice
country: Slovakia
facility: 205.446.42101 Boehringer Ingelheim Investigational Site
city: Presov
country: Slovakia
facility: 205.446.42103 Boehringer Ingelheim Investigational Site
city: Spisska Nova Ves
country: Slovakia
facility: 205.446.42102 Boehringer Ingelheim Investigational Site
city: Chernivtsi
country: Ukraine
facility: 205.446.38013 Boehringer Ingelheim Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: 205.446.38002 Boehringer Ingelheim Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: 205.446.38003 Boehringer Ingelheim Investigational Site
city: Donetsk
country: Ukraine
facility: 205.446.38005 Boehringer Ingelheim Investigational Site
city: Donetsk
country: Ukraine
facility: 205.446.38012 Boehringer Ingelheim Investigational Site
city: Kharkiv
country: Ukraine
facility: 205.446.38009 Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 205.446.38004 Boehringer Ingelheim Investigational Site
city: Kriviy Rig
country: Ukraine
facility: 205.446.38006 Boehringer Ingelheim Investigational Site
city: Lviv
country: Ukraine
facility: 205.446.38001 Boehringer Ingelheim Investigational Site
city: Odesa
country: Ukraine
facility: 205.446.38014 Boehringer Ingelheim Investigational Site
city: Vinnytsya
country: Ukraine
facility: 205.446.38010 Boehringer Ingelheim Investigational Site
city: Zaporizhya
country: Ukraine
facility: 205.446.38011 Boehringer Ingelheim Investigational Site
city: Zaporizhzhya
country: Ukraine
facility: 205.446.38008 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: