Clinical trial NCT01122680: Efficacy and Safety of 3 Doses of Tiotropium Compared to Placebo in Adolescents (12 to 17 Yrs) 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 Adolescents (12 to 17 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: 2010-05-13
Enrollment: 105
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is to evaluate the efficacy and safety of tiotropium 1.25 mcg (2 actuations of 0.625 mcg), tiotropium 2.5 mcg (2 actuations of 1.25 mcg) and tiotropium 5 mcg (2 actuations of 2.5 mcg) once daily in the evening delivered by the Respimat inhaler in adolescents (12 to 17 yrs) with moderate persistent asthma, compared to placebo and on top of maintenance therapy with an inhaled corticosteroid controller medication. It is a randomised, double-blind, placebo-controlled Phase II trial with incomplete cross-over design. Patients need to be still symptomatic, i. e. not fully controlled with their maintenance treatment.


Eligibility criteria: Inclusion criteria:

1. All patients and legally accepted caregiver(s) must sign and date an Informed Consent form consistent with Good Clinical Practice (GCP) guidelines of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and local legislation prior to participation in the trial.
2. Male or female patients between 12 and 17 years of age.
3. All patients must have at least a 3 months history of asthma and fulfill the diagnostic criteria of moderate persistent asthma, according to the current Global Initiative for Asthma (GINA) guidelines 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 for at least 4 weeks before Visit 1.
5. All patients must be symptomatic (partly controlled) at Visit 1 (screening) and prior to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ) mean score of equal or above 1.5.
6. All patients must have a pre-bronchodilator FEV1 above 60% and less than or equal 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%.
7. All patients must have an increase in FEV1 of equal or above 12% and 200 mL 15 min. after 400 mcg 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.
8. All patients should be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment.
9. Patients should be able to use the Respimat® inhaler correctly.
10. Patients must be able to perform all trial related procedures including technically acceptable spirometric manoeuvres, according to American Thoracic Society (ATS) standards and the use of the electronic diary/peak flow meter.

Exclusion criteria:

1. Patients with a significant disease other than asthma.
2. Patients with a history of congenital or acquired heart disease, and/or have been hospitalised for cardiac syncope or failure during the past year.
3. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention (e. g. pacemaker implantation) or a change in drug therapy within the past year.
4. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.
5. Patients with lung diseases other than asthma, e.g. cystic fibrosis (CF). In case of ex-premature infants, a history of significant bronchopulmonary dysplasia (BPD) will be regarded as exclusion criterion
6. Patients with significant alcohol or drug abuse within the past two years.
7. Patients with known hypersensitivity to anticholinergic drugs, benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA) or any other components of the tiotropium inhalation solution.
8. Pregnant or nursing adolescent female patients, including female patients with a positive Beta HCG (serum pregnancy) testing at screening (visit 1).
9. Sexually active female patients of child-bearing potential not using a highly effective method of birth control.
10. Patients with a known narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated.
11. Patients with renal impairment, as defined by a creatinine clearance less than 50 mL/min/1.73 m2 body surface area (BSA) as calculated by Schwartz Formula.

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: FEV1 Area Under the Curve From 0 to 3 h (AUC0-3h) Response
timeFrame: Baseline and 4 weeks
measure: FEV1 Individual Measurements Response at Each Time-point
timeFrame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
measure: Forced Vital Capacity (FVC) Peak (0-3h) Response
timeFrame: Baseline and 4 weeks
measure: FVC Trough 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: FVC Individual Measurements at Each Time-point
timeFrame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
measure: Forced Expiratory Flow (FEF) 25-75% Individual Measurements Response at Each Time Point
timeFrame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
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 Day
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: Denver
country: United States
facility: 205.424.01002 Boehringer Ingelheim Investigational Site
state: Colorado
city: Columbia
country: United States
facility: 205.424.01006 Boehringer Ingelheim Investigational Site
state: Missouri
city: Warrensburg
country: United States
facility: 205.424.01007 Boehringer Ingelheim Investigational Site
state: Missouri
city: Boys Town
country: United States
facility: 205.424.01004 Boehringer Ingelheim Investigational Site
state: Nebraska
city: Canton
country: United States
facility: 205.424.01001 Boehringer Ingelheim Investigational Site
state: Ohio
city: Koblenz
country: Germany
facility: 205.424.49007 Boehringer Ingelheim Investigational Site
city: Rosenheim
country: Germany
facility: 205.424.49004 Boehringer Ingelheim Investigational Site
city: Wesel
country: Germany
facility: 205.424.49002 Boehringer Ingelheim Investigational Site
city: Balvi
country: Latvia
facility: 205.424.37104 Boehringer Ingelheim Investigational Site
city: Daugavpils
country: Latvia
facility: 205.424.37103 Boehringer Ingelheim Investigational Site
city: Rezekne
country: Latvia
facility: 205.424.37105 Boehringer Ingelheim Investigational Site
city: Riga
country: Latvia
facility: 205.424.37101 Boehringer Ingelheim Investigational Site
city: Riga
country: Latvia
facility: 205.424.37102 Boehringer Ingelheim Investigational Site
city: Vilnius
country: Lithuania
facility: 205.424.37001 Boehringer Ingelheim Investigational Site
city: Vilnius
country: Lithuania
facility: 205.424.37003 Boehringer Ingelheim Investigational Site
city: Vilnius
country: Lithuania
facility: 205.424.37004 Boehringer Ingelheim Investigational Site
city: Kamnik
country: Slovenia
facility: 205.424.38604 Boehringer Ingelheim Investigational Site
city: Ljubljana
country: Slovenia
facility: 205.424.38605 Boehringer Ingelheim Investigational Site
city: Maribor
country: Slovenia
facility: 205.424.38602 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Vogelberg C, Engel M, Moroni-Zentgraf P, Leonaviciute-Klimantaviciene M, Sigmund R, Downie J, Nething K, Vevere V, Vandewalker M. Tiotropium in asthmatic adolescents symptomatic despite inhaled corticosteroids: a randomised dose-ranging study. Respir Med. 2014 Sep;108(9):1268-76. doi: 10.1016/j.rmed.2014.06.011. Epub 2014 Jul 17.