Clinical trial NCT01383499: A Study to Evaluate Efficacy and Safety of Tiotropium in Children 6 to 11 Years Old With Moderate Asthma
Official title: A Phase II Randomised, Double-blind, Placebo-controlled Incomplete Crossover Trial With 4-week Treatment Periods to Evaluate Efficacy and Safety of Tiotropium Inhalation Solution (Doses of 1.25 µg, 2.5 µg and 5 µg) Delivered Via Respimat® Inhaler Once Daily in the Evening in Children 6 to 11 Yrs Old With Moderate Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2011-06-28
Enrollment: 101
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The aim of this trial is to select an optimum dose may be selected based on bronchodilator efficacy, safety evaluations and pharmacokinetics of tiotropium bromide.


Eligibility criteria: Inclusion criteria:

Patients must meet all of the following inclusion criteria to be eligible for enrollment into this study:

1. All patients' parents (or legally accepted caregivers) must sign and date an informed consent prior to any study procedures including medication washout and restrictions. In addition, an informed assent suitable for this age group has to be obtained from patients.
2. Male or female patients between 6 and 11 years of age (up to 1 day prior to their 12th birthday at Visit 1).
3. All patients must have at least a 6-month history of asthma at the time of enrolment into the trial.
4. All patients must have been on maintenance treatment with inhaled corticosteroids at a stable medium dose - a patient is eligible on =200 µg to =400 µg Budesonide DPI or equivalent.
5. All patients must be symptomatic (partly controlled) at Visit 1 (screening) and prior to randomisation at Visit 2 as defined by an ACQ mean score of =1.5.
6. All patients must have a pre-bronchodilator FEV1 =60% and =90% of predicted normal at Visit 1. Variation of absolute FEV1 values of Visit 2 (pre-dose) as compared to values at Visit 2 (pre-bronchodilator) must be within ± 30%.
7. All patients must demonstrate an increase in FEV1 of =12% 15 to 30 min. after 200 µg salbutamol (albuterol) at Visit 1.
8. Patients must be able to inhale from the Respimat® inhaler correctly.
9. Patients must be able to perform all trial related procedures including technically acceptable spirometric manoeuvres according to current ATS/ERS standards and the use of the electronic diary/peak flow meter.

Exclusion criteria:

Patients with any of the following characteristics will not be eligible for entry into this study:

1. Patients with a significant disease other than asthma.
2. Patients with clinically relevant abnormal screening haematology or blood chemistry will be excluded if the abnormality defines a significant disease as defined in exclusion criterion 1. For participation in PK sampling, a haemoglobin of less than 11.3 g/dL will be regarded as exclusion criterion.
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, including cardiac arrhythmia requiring intervention (e.g. pacemaker implantation, catheter ablation etc.) 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 clinically significant lung diseases other than asthma, such as CF, or bronchopulmonary dysplasia.
7. Patients with known active tuberculosis.
8. Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1.
9. 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).
10. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the tiotropium inhalation solution.
11. Patients with known narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated.
12. 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: Forced Expiratory Volume (FEV1) Peak (0-3h) Response
timeFrame: Baseline and 4 weeks
Secondary outcomes:
measure: Trough FEV1 Response
timeFrame: Baseline and 4 weeks
measure: Forced Vital Capacity (FVC) Peak (0-3h) Response
timeFrame: Baseline and 4 weeks
measure: FVC Trough Response
timeFrame: Baseline and 4 weeks
measure: FEV1 Area Under the Curve From 0 to 3 h (AUC0-3h) Response
timeFrame: Baseline and 4 weeks
measure: FVC Area Under the Curve From 0 to 3 h (AUC0-3h) Response
timeFrame: Baseline and 4 weeks
measure: Mean Morning Peak Expiratory Flow (PEF) Response
timeFrame: Baseline and 4 weeks
measure: Mean Evening PEF Response
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the Number of Puffs of Rescue Medication Per Period (24 h, Daytime and Night-time Use)
timeFrame: Baseline and 4 weeks
measure: Control of Asthma as Assessed by Asthma Control Questionnaire (ACQ)
timeFrame: 4 weeks
measure: Change From Baseline in Mean Number of Nighttime Awakenings
timeFrame: Baseline and last week of treatment (week 4)
Other outcomes:
Locations:
city: Bochum
country: Germany
facility: 205.425.49005 Boehringer Ingelheim Investigational Site
city: Dresden
country: Germany
facility: 205.425.49004 Boehringer Ingelheim Investigational Site
city: Koblenz
country: Germany
facility: 205.425.49002 Boehringer Ingelheim Investigational Site
city: Budapest
country: Hungary
facility: 205.425.36001 Boehringer Ingelheim Investigational Site
city: Budapest
country: Hungary
facility: 205.425.36003 Boehringer Ingelheim Investigational Site
city: Mosdos
country: Hungary
facility: 205.425.36002 Boehringer Ingelheim Investigational Site
city: Szeged
country: Hungary
facility: 205.425.36004 Boehringer Ingelheim Investigational Site
city: Baldone
country: Latvia
facility: 205.425.37101 Boehringer Ingelheim Investigational Site
city: Balvi
country: Latvia
facility: 205.425.37105 Boehringer Ingelheim Investigational Site
city: Daugavpils
country: Latvia
facility: 205.425.37104 Boehringer Ingelheim Investigational Site
city: Dubulti
country: Latvia
facility: 205.425.37106 Boehringer Ingelheim Investigational Site
city: Riga
country: Latvia
facility: 205.425.37102 Boehringer Ingelheim Investigational Site
city: Riga
country: Latvia
facility: 205.425.37103 Boehringer Ingelheim Investigational Site
city: Kaunas
country: Lithuania
facility: 205.425.37004 Boehringer Ingelheim Investigational Site
city: Taurage
country: Lithuania
facility: 205.425.37003 Boehringer Ingelheim Investigational Site
city: Vilnius
country: Lithuania
facility: 205.425.37001 Boehringer Ingelheim Investigational Site
city: Vilnius
country: Lithuania
facility: 205.425.37002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 205.425.07003 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 205.425.07004 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 205.425.07001 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 205.425.07002 Boehringer Ingelheim Investigational Site
city: Donetsk
country: Ukraine
facility: 205.425.38002 Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 205.425.38004 Boehringer Ingelheim Investigational Site
city: Zaporizhya
country: Ukraine
facility: 205.425.38003 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Vogelberg C, Moroni-Zentgraf P, Leonaviciute-Klimantaviciene M, Sigmund R, Hamelmann E, Engel M, Szefler S. A randomised dose-ranging study of tiotropium Respimat(R) in children with symptomatic asthma despite inhaled corticosteroids. Respir Res. 2015 Feb 7;16(1):20. doi: 10.1186/s12931-015-0175-9.