A Study to Evaluate Efficacy and Safety of Tiotropium in Children 6 to 11 Years Old With Moderate Asthma

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01383499
First received: June 20, 2011
Last updated: December 4, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Tiotropium bromide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Forced Expiratory Volume (FEV1) Peak (0-3h) Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Trough FEV1 Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Forced Vital Capacity (FVC) Peak (0-3h) Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    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.

  • FVC Trough Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    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.

  • FEV1 Area Under the Curve From 0 to 3 h (AUC0-3h) Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    FEV1 (AUC0-3h) will be calculated as the area under the curve from 0 to 3 hours 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.

  • FVC Area Under the Curve From 0 to 3 h (AUC0-3h) Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    FVC (AUC0-3h) will be calculated as the area under the curve from 0 to 3 hours 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.

  • Mean Morning Peak Expiratory Flow (PEF) Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Mean Evening PEF Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in the Number of Puffs of Rescue Medication Per Period (24 h, Daytime and Night-time Use) [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    Mean number of inhalations (puffs) of unscheduled rescue salbutamol therapy during whole day (24 h, daytime and night-time use). Analysis adjusted for treatment, period, patient and baseline using a mixed model.

  • Control of Asthma as Assessed by Asthma Control Questionnaire (ACQ) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    ACQ is a questionnaire consisting of 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.

  • Change From Baseline in Mean Number of Nighttime Awakenings [ Time Frame: Baseline and last week of treatment (week 4) ] [ Designated as safety issue: No ]
    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. The scores for this question used the following scale where: 1='Did not wake up', 2='Woke up once', 3='Woke up 2-5 times', 4='Woke up more than 5 times' and 5='Was awake all night'.


Enrollment: 101
Study Start Date: August 2011
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A
patients inhale 2 puffs (low dose) once daily in the evening via Respimat inhaler
Drug: Tiotropium bromide
inhalation solution administered via Respimat in 3 different doses
Experimental: Treatment B
patients inhale 2 puffs (medium dose) once daily in the evening via Respimat inhaler
Drug: Tiotropium bromide
inhalation solution administered via Respimat in 3 different doses
Experimental: Treatment C
patients inhale 2 puffs (high dose) once daily in the evening via Respimat inhaler
Drug: Tiotropium bromide
inhalation solution administered via Respimat in 3 different doses
Placebo Comparator: Treatment D
patients inhale 2 puffs of placebo inhalation solution matching tiotropium once daily in the evening via Respimat inhaler
Drug: Tiotropium bromide
inhalation solution administered via Respimat in 3 different doses

  Eligibility

Ages Eligible for Study:   6 Years to 11 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01383499

Locations
Germany
205.425.49005 Boehringer Ingelheim Investigational Site
Bochum, Germany
205.425.49004 Boehringer Ingelheim Investigational Site
Dresden, Germany
205.425.49002 Boehringer Ingelheim Investigational Site
Koblenz, Germany
Hungary
205.425.36001 Boehringer Ingelheim Investigational Site
Budapest, Hungary
205.425.36003 Boehringer Ingelheim Investigational Site
Budapest, Hungary
205.425.36002 Boehringer Ingelheim Investigational Site
Mosdos, Hungary
205.425.36004 Boehringer Ingelheim Investigational Site
Szeged, Hungary
Latvia
205.425.37101 Boehringer Ingelheim Investigational Site
Baldone, Latvia
205.425.37105 Boehringer Ingelheim Investigational Site
Balvi, Latvia
205.425.37104 Boehringer Ingelheim Investigational Site
Daugavpils, Latvia
205.425.37106 Boehringer Ingelheim Investigational Site
Dubulti, Latvia
205.425.37102 Boehringer Ingelheim Investigational Site
Riga, Latvia
205.425.37103 Boehringer Ingelheim Investigational Site
Riga, Latvia
Lithuania
205.425.37004 Boehringer Ingelheim Investigational Site
Kaunas, Lithuania
205.425.37003 Boehringer Ingelheim Investigational Site
Taurage, Lithuania
205.425.37002 Boehringer Ingelheim Investigational Site
Vilnius, Lithuania
205.425.37001 Boehringer Ingelheim Investigational Site
Vilnius, Lithuania
Russian Federation
205.425.07003 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
205.425.07004 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
205.425.07001 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
205.425.07002 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
Ukraine
205.425.38002 Boehringer Ingelheim Investigational Site
Donetsk, Ukraine
205.425.38004 Boehringer Ingelheim Investigational Site
Kiev, Ukraine
205.425.38003 Boehringer Ingelheim Investigational Site
Zaporizhya, Ukraine
Sponsors and Collaborators
Boehringer Ingelheim
Pfizer
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01383499     History of Changes
Other Study ID Numbers: 205.425, 2010-022458-18
Study First Received: June 20, 2011
Results First Received: September 23, 2013
Last Updated: December 4, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Russia: Pharmacological Committee, Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Bromides
Tiotropium
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014