Efficacy and Safety of 2 Doses of Tiotropium Via Respimat Compared to Placebo in Adolescents With Moderate Persistent Asthma

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01257230
First received: December 6, 2010
Last updated: January 8, 2014
Last verified: January 2014
  Purpose

The aim of the study is to evaluate efficacy and safety of a 48-week treatment with two doses of tiotropium bromide compared to placebo in adolescent patients with moderate persistent asthma. Efficacy and safety will be assessed by measuring lung function parameters and evaluating the effects on asthma exacerbations, on Quality of life, on health care resource utilisation an on the number of adverse events.


Condition Intervention Phase
Asthma
Drug: tiotropium Respimat low dose
Drug: placebo Respimat
Drug: tiotropium Respimat high dose
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase III, Randomised, Double Blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety Over 48 Weeks of Orally Inhaled Tiotropium Bromide (2.5 and 5 µg Once Daily ) Delivered by the Respimat® Inhaler in Adolescents (12 to 17 Years Old) With Moderate Persistent Asthma.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Peak Forced expiratory Flow in 1 second response within 3 hours post dosing (FEV1 peak0-3 response) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Trough FEV1at 12 weeks [ Time Frame: 12weeks ] [ Designated as safety issue: No ]
  • Peak forced vital capacity within 3 hours post dosing (FVC peak0-3), and trough FVC at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • FEV1 (AUC0-3) and FVC (AUC0-3) (AUC = Area Under the Curve) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • mean forced expiratory flow between 25% and 75% of the FVC (FEF25-75) at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Use of PRN rescue medication (salbutamol/albuterol) [ Time Frame: weekly means for 48 weeks ] [ Designated as safety issue: No ]
  • Control of asthma as assessed by the Asthma Control Questionnaire (ACQ) at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Time to first severe asthma exacerbation; time to first asthma exacerbation [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Trough FEV1 at 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Trough FEV1 at 48 weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Peak forced vital capacity within 3 hours post dosing (FVC peal0-3), and trough FVC at 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Peak forced vital capacity within 3 hours post dosing (FVC peak0-3), and trough FVC at 48 weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • FEV1 (AUC0-3) and FVC (AUC0-3) at week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • FEV1 (AUC0-3) and FVC (AUC0-3) at week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Control of asthma as assessed by the Asthma Control Questionnaire (ACQ) at week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Control of asthma as assessed by the Asthma Control Questionnaire (ACQ) at week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • mean forced expiratory flow between 25% and 75% of the FVC (FEF25-75) at week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • mean forced expiratory flow between 25% and 75% of the FVC (FEF25-75) at week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Enrollment: 398
Study Start Date: December 2010
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo
once daily, delivered with Respimat inhaler
Drug: placebo Respimat
placebo representing comparator
Experimental: tiotropium low dose
once daily, delivered with Respimat inhaler
Drug: tiotropium Respimat low dose
IMP
Experimental: tiotropium high dose
once daily, delivered with Respimat inhaler
Drug: tiotropium Respimat high dose
IMP

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. All patients and their parents (or legally accepted caregiver) must sign and date an informed consent consistent with ICH-GCP guidelines 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 at the time of enrolment into the trial. The diagnosis of asthma has to be confirmed at visit 1 with a bronchodilator reversibility test.
  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 at randomisation defined by an Asthma Control Questionnaire (ACQ) mean score of more than or equal to 1.5.
  6. All patients must have a pre-bronchodilator FEV1 more than or equal to 60% and less than or equal to 90% of predicted normal at Visit 1. Variation of absolute FEV1 values of Visit 1 as compared to Visit 2 must be within ± 30%.
  7. All patients must have an increase in FEV1 of equal or above 12% and 200 mL after 400 µg 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.

Exclusion criteria:

  1. Patients with a significant disease other than asthma.
  2. Patients with clinically relevant abnormal screening haematology or blood chemistry
  3. Patients with a history of congenital or acquired heart disease, and/or 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 malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.
  6. Patients with lung diseases other than asthma (e.g. Cystic Fibrosis). In case of ex-premature infants, a history of significant bronchopulmonary dysplasia will be regarded as exclusion criterion.
  7. Patients with known active tuberculosis.
  8. Patients with significant alcohol or drug abuse within the past two years.
  9. Patients who have undergone thoracotomy with pulmonary resection.
  10. 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).
  11. Patients with known hypersensitivity to anticholinergic drugs, Benzalkonium chloride (BAC), Ethylenediaminetetraacetic acis (EDTA) or any other components of the tiotropium inhalation solution.
  12. Pregnant or nursing adolescent female patients
  13. Sexually active female patients of child-bearing potential not using a highly effective method of birth control.
  14. Patients who have taken an investigational drug within 4 weeks prior to Visit 1.
  15. Patients who have been treated with long-acting anticholinergics (e.g. tiotropium -Spiriva) within four weeks prior to screening (Visit 1).
  16. Patients who are unable to comply with pulmonary medication restrictions prior to randomisation.
  17. Patients who have been treated with Anti-IgE treatment (Omalizumab Xolair) within the last 6 months prior to screening.
  18. Patients who have been treated with systemic (oral or intravenous) corticosteroids within 4 weeks prior to screening (Visit 1).
  19. Patients who have been treated with long-acting theophylline preparations within 2 weeks prior to screening (Visit 1) or during the run-in period
  20. Patients who have been treated with other non-approved and according to international guidelines not recommended ¿experimental¿ drugs for routine asthma therapy.
  21. Patients with any acute asthma exacerbation or respiratory tract infection in the 4 weeks prior to Visit 1.
  22. Patients requiring 10 or more puffs of rescue medication (salbutamol/albuterol) per day on more than 2 consecutive days during the run-in period.
  23. Patients who have previously been randomised in this trial or are currently participating in another study.
  24. Patients who are being treated with oral beta-blocker medication.
  25. Patients with a known narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated.
  26. Patients with renal impairment, as defined by a creatinine clearance less than 50 mL/min/1.73 m2 Body Surface Area as calculated by Schwartz formula.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01257230

  Show 66 Study Locations
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: NCT01257230     History of Changes
Other Study ID Numbers: 205.444, 2010-021093-11
Study First Received: December 6, 2010
Last Updated: January 8, 2014
Health Authority: Chile: Instituto de Salud Publica de Chile
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: Ethics Committee
Latvia: State Agency of Medicines
Mexico: Federal Commission for Protection Against Health Risks
Russia: Pharmacological Committee, Ministry of Health
Slovakia: State Institute for Drug Control
South Korea: Ministry of Food and Drug Safety (MFDS)
Spain: Spanish Agency of Medicines
Ukraine: State Pharmacological Center - Ministry of Health
United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 23, 2014