- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01122680
Efficacy and Safety of 3 Doses of Tiotropium Compared to Placebo in Adolescents (12 to 17 Yrs) With Moderate Asthma
May 7, 2014 updated by: Boehringer Ingelheim
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
105
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Koblenz, Germany
- 205.424.49007 Boehringer Ingelheim Investigational Site
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Rosenheim, Germany
- 205.424.49004 Boehringer Ingelheim Investigational Site
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Wesel, Germany
- 205.424.49002 Boehringer Ingelheim Investigational Site
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Balvi, Latvia
- 205.424.37104 Boehringer Ingelheim Investigational Site
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Daugavpils, Latvia
- 205.424.37103 Boehringer Ingelheim Investigational Site
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Rezekne, Latvia
- 205.424.37105 Boehringer Ingelheim Investigational Site
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Riga, Latvia
- 205.424.37101 Boehringer Ingelheim Investigational Site
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Riga, Latvia
- 205.424.37102 Boehringer Ingelheim Investigational Site
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Vilnius, Lithuania
- 205.424.37001 Boehringer Ingelheim Investigational Site
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Vilnius, Lithuania
- 205.424.37003 Boehringer Ingelheim Investigational Site
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Vilnius, Lithuania
- 205.424.37004 Boehringer Ingelheim Investigational Site
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Kamnik, Slovenia
- 205.424.38604 Boehringer Ingelheim Investigational Site
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Ljubljana, Slovenia
- 205.424.38605 Boehringer Ingelheim Investigational Site
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Maribor, Slovenia
- 205.424.38602 Boehringer Ingelheim Investigational Site
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Colorado
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Denver, Colorado, United States
- 205.424.01002 Boehringer Ingelheim Investigational Site
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Missouri
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Columbia, Missouri, United States
- 205.424.01006 Boehringer Ingelheim Investigational Site
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Warrensburg, Missouri, United States
- 205.424.01007 Boehringer Ingelheim Investigational Site
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Nebraska
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Boys Town, Nebraska, United States
- 205.424.01004 Boehringer Ingelheim Investigational Site
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Ohio
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Canton, Ohio, United States
- 205.424.01001 Boehringer Ingelheim Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
12 years to 17 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion criteria:
- 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.
- Male or female patients between 12 and 17 years of age.
- 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.
- 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 prior to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ) mean score of equal or above 1.5.
- 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%.
- 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.
- 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, according to American Thoracic Society (ATS) standards and the use of the electronic diary/peak flow meter.
Exclusion criteria:
- Patients with a significant disease other than asthma.
- 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 (e. g. pacemaker implantation) 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 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
- Patients with significant alcohol or drug abuse within the past two years.
- Patients with known hypersensitivity to anticholinergic drugs, benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA) or any other components of the tiotropium inhalation solution.
- Pregnant or nursing adolescent female patients, including female patients with a positive Beta HCG (serum pregnancy) testing at screening (visit 1).
- Sexually active female patients of child-bearing potential not using a highly effective method of birth control.
- Patients with a known narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Treatment A
patients inhale 2 puffs (dose of 1.25 mcg) once daily in the evening via Respimat inhaler
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inhalation solution, dose of 1.25 mcg (2 puffs of 0.625 mcg)
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Experimental: Treatment C
patients inhale 2 puffs (dose of 5 mcg) once daily in the evening via Respimat inhaler
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inhalation solution, dose of 2.5 mcg (2 puffs of 1.25 mcg)
inhalation solution, dose of 5 mcg (2 puffs of 2.5 mcg)
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Placebo Comparator: Placebo
patients inhale 2 puffs of placebo matching tiotropium once daily in the evening via Respimat inhaler
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placebo inhalation solution
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Experimental: Treatment B
patients inhale 2 puffs (dose of 2.5 mcg) once daily in the evening via Respimat inhaler
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inhalation solution, dose of 2.5 mcg (2 puffs of 1.25 mcg)
inhalation solution, dose of 5 mcg (2 puffs of 2.5 mcg)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Forced Expiratory Volume (FEV1) Peak (0-3h) Response
Time Frame: Baseline and 4 weeks
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The FEV1 peak (0-3h) response is determined at the end of the 4 week treatment period.
This is the difference between the maximum FEV1 measured within the first 3 hours post dosing and the FEV1 baseline measurement.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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Baseline and 4 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Trough FEV1 Response
Time Frame: Baseline and 4 weeks
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The trough FEV1 is defined as the pre-dose FEV1 measured just prior to the last administration of randomised treatment.
Response was defined as the change from baseline.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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Baseline and 4 weeks
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FEV1 Area Under the Curve From 0 to 3 h (AUC0-3h) Response
Time Frame: Baseline and 4 weeks
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FEV1 (AUC0-3h) will be calculated as the area under the curve from 0 to 3hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres.
Response was defined as the change from baseline.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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Baseline and 4 weeks
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FEV1 Individual Measurements Response at Each Time-point
Time Frame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
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Individual FEV1 measurements at each time-point ("personal best").
Response was defined as the change from baseline.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
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Forced Vital Capacity (FVC) Peak (0-3h) Response
Time Frame: Baseline and 4 weeks
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The FVC peak (0-3h) response is determined at the end of the 4 week treatment period.
This is the difference between the maximum FVC measured within the first 3 hours post dosing and the FVC baseline measurement.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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Baseline and 4 weeks
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FVC Trough Response
Time Frame: Baseline and 4 weeks
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The trough FVC response is defined as the pre-dose FVC measured just prior to the last administration of randomised treatment.
Response was defined as the change from baseline.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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Baseline and 4 weeks
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FVC Area Under the Curve From 0 to 3 h (AUC0-3h) Response
Time Frame: Baseline and 4 weeks
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FVC (AUC0-3h) will be calculated as the area under the curve from 0 to 3hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres.
Response was defined as the change from baseline.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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Baseline and 4 weeks
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FVC Individual Measurements at Each Time-point
Time Frame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
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Individual FVC measurements at each time-point ("personal best").
Response was defined as the change from baseline.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
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Forced Expiratory Flow (FEF) 25-75% Individual Measurements Response at Each Time Point
Time Frame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
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FEF 25-75% is the mean forced expiratory flow between 25% and 75% of the FVC determined at the end of the 4-week treatment period.
This is often referred to as the maximum midexpiratory flow.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
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Mean Morning Peak Expiratory Flow (PEF) Response
Time Frame: Baseline and 4 weeks
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Mean morning PEF assessed by patients at home.
Response was defined as the change from baseline.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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Baseline and 4 weeks
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Mean Evening PEF Response
Time Frame: Baseline and 4 weeks
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Mean evening PEF assessed by patients at home.
Response was defined as the change from baseline.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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Baseline and 4 weeks
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Change From Baseline in the Number of Puffs of Rescue Medication Per Day
Time Frame: Baseline and 4 weeks
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Mean number of inhalations (puffs) of unscheduled rescue salbutamol therapy during whole day.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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Baseline and 4 weeks
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Control of Asthma as Assessed by Asthma Control Questionnaire (ACQ)
Time Frame: 4 weeks
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ACQ is a questionnaire consisting of a seven point Likert scale ranging from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma.
The scale describes the frequency and severity of asthma symptoms.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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4 weeks
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Change From Baseline in Mean Number of Nighttime Awakenings
Time Frame: Baseline and last week of treatment (week 4)
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Mean number of nighttime awakenings due to asthma symptoms as assessed by patients eDiary incorporated in the AM3® device.
Analysis adjusted for treatment, period, patient and baseline using a mixed model.
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Baseline and last week of treatment (week 4)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2010
Primary Completion (Actual)
April 1, 2011
Study Registration Dates
First Submitted
May 11, 2010
First Submitted That Met QC Criteria
May 11, 2010
First Posted (Estimate)
May 13, 2010
Study Record Updates
Last Update Posted (Estimate)
May 16, 2014
Last Update Submitted That Met QC Criteria
May 7, 2014
Last Verified
July 1, 2012
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Immune System Diseases
- Lung Diseases
- Hypersensitivity, Immediate
- Bronchial Diseases
- Lung Diseases, Obstructive
- Respiratory Hypersensitivity
- Hypersensitivity
- Asthma
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Parasympatholytics
- Autonomic Agents
- Peripheral Nervous System Agents
- Cholinergic Antagonists
- Cholinergic Agents
- Anticonvulsants
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Tiotropium Bromide
- Bromides
Other Study ID Numbers
- 205.424
- 2009-017745-55 (EudraCT Number: EudraCT)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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