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

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01277523
First received: January 13, 2011
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

The overall purpose of the trial is to evaluate efficacy and safety of tiotropium inhalation solution delivered via Respimat® inhaler (2.5 mcg and 5 mcg once daily) over 12 weeks, compared to placebo, as add-on controller therapy on top of usual care in adolescents (12 to 17 years old) with severe persistent asthma.

The primary objective of the trial is to demonstrate superiority of tiotropium (5 mcg and possibly 2.5 mcg once daily in the evening) over placebo with regard to the primary pulmonary function endpoint after 12 weeks of treatment.

Secondary objectives are to evaluate efficacy of tiotropium with regard to other endpoints, and to evaluate the safety of tiotropium, compared to placebo, as add-on controller therapy on top of usual care in this patient population.


Condition Intervention Phase
Asthma
Drug: tiotropium high dose
Drug: placebo
Drug: tiotropium low 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 Randomised, Double-blind, Placebo-controlled, Parallel-group Trial to Evaluate Efficacy and Safety of Tiotropium Inhalation Solution Delivered Via Respimat® Inhaler (2.5 mcg and 5 mcg Once Daily) Over 12 Weeks as add-on Controller Therapy on Top of Usual Care in Adolescents (12 to 17 Years Old) With Severe Persistent Asthma

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change from baseline at the end of the 12-week treatment period in the highest forced expiratory volume in one second reading observed within 3 hours after administration of the evening dose of each randomised treatment (peak FEV1 response). [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline at the end of the 12-week treatment period in the trough forced expiratory volume in one second (trough FEV1 response). [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline at the end of the 12-week treatment period in the highest forced vital capacity reading observed within 3 hours after administration of the evening dose of each randomised treatment. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline at the end of the 12-week treatment period in the area under the curve from zero to 3 hours of the trough forced expiratory volume and the forced vital capacity. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • The number of responders (improvement of at least 0.5 for the ACQ) as assessed by the Asthma Control Questionnaire (ACQ) determined at the end of the 12-week treatment period. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Number of inhalations of salbutamol (albuterol) rescue medication used per day during the 12-week treatment period. [ Time Frame: 0-12 weeks ] [ Designated as safety issue: No ]
  • Time to first severe asthma exacerbation during the 12-week treatment period. [ Time Frame: 0-12 weeks ] [ Designated as safety issue: No ]
  • Time to first asthma exacerbation during the 12-week treatment period. [ Time Frame: 0-12 weeks ] [ Designated as safety issue: No ]

Enrollment: 392
Study Start Date: January 2011
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: tiotropium low dose
2 actuations once daily
Experimental: B Drug: tiotropium high dose
2 actuations once daily
Placebo Comparator: C Drug: placebo
2 actuations once daily

  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 parent(s) (or legally accepted representative) must sign and date respectively an informed assent and an informed consent consistent with International Conference on Harmonisation - Harmonised Tripartite Guideline for Good Clinical Practice (ICH-GCP) guidelines and local legislation prior to the patient's participation in the trial. A separate informed consent/assent is required for pharmacogenomic sampling.
  2. Male or female patients between 12 and 17 years of age (at date of informed consent/assent).
  3. All patients must have at least a 3-month history of asthma at the time of enrolment into the trial.
  4. All patients must have been on maintenance treatment with an inhaled corticosteroid either at stable high dose in combination with another controller medication, OR at stable medium dose in combination with two other controller medications, for at least 4 weeks before Visit 1.
  5. All patients must be symptomatic at Visit 1 (screening) and prior to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ) mean score of = 1.5.
  6. All patients must have a pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) = 60% and = 90% of predicted normal at Visit 1.
  7. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator, considered as 100%) as compared to Visit 2 (pre-dose) must be within ± 30%.
  8. All patients must confirm the diagnosis of asthma by bronchodilator reversibility at Visit 1, resulting in an increase in FEV1 of = 12% and = 200 mL 15 to 30 minutes after 400 µg salbutamol (albuterol). If patients in the lower age range (e.g. 12 to 14 year old patients) exhibit a very small total lung volume, positive reversibility testing might be based solely on the relative (=12%) post-bronchodilator response.
  9. All patients must be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment.
  10. Patients must be able to use the Respimat® inhaler correctly.
  11. Patients must be able to perform all trial related procedures including technically acceptable spirometric manoeuvres according to American Thoracic Society/ European Respiratory Society (ATS/ERS) standards and use of the electronic diary/peak flow meter (diary compliance of at least 80% is required).

Exclusion criteria:

  1. Significant disease other than asthma.
  2. Abnormal haematology or blood chemistry.
  3. History of heart disease, and/or hospitalised for cardiac syncope or failure.
  4. Any unstable or life-threatening or requiring intervention or cardiac arrhythmia.
  5. Malignancy for which the patient has undergone resection, radiation therapy or chemotherapy.
  6. Active tuberculosis.
  7. Alcohol or drug abuse.
  8. Thoracotomy with pulmonary resection.
  9. Pulmonary rehabilitation program.
  10. Hypersensitivity to anticholinergic drugs, or any components of the study medication delivery system.
  11. Pregnant or nursing adolescent female patients.
  12. Female patients of child-bearing potential not using a highly effective method of birth control.
  13. Investigational drug within four weeks or six half lives prior to Visit 1.
  14. Long-acting anticholinergics within four weeks prior to Visit 1.
  15. Systemic corticosteroids at a high dose or at a not stable low dose within four weeks prior to Visit 1.
  16. Leukotriene modifiers if not stabilised for at least four weeks prior to Visit 1.
  17. Long-acting theophylline preparations if not stabilised for at least two weeks prior to Visit 1.
  18. Anti Immunoglobulin E (Anti-IgE) treatment if not stabilised for at least six months prior to Visit 1.
  19. Cromones if not stabilised within four weeks prior to Visit 1.
  20. Oral beta-blocker medication within four weeks prior to Visit 1.
  21. Systemic oral or i.v. or s.c. beta-adrenergics within four weeks prior to Visit 1.
  22. Other non-approved and according to international guidelines not recommended experimental drugs for routine asthma therapy within four weeks prior to Visit 1.
  23. Any acute asthma exacerbation or respiratory tract infection in the four weeks prior to Visit 1and/or in the four weeks prior to Visit 2. In case of an asthma deterioration occurring in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2, the visit must be postponed.
  24. Randomised in this trial or currently participating in another trial.
  25. Narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated.
  26. Moderate to severe renal impairment.
  27. Patients requiring 10 or more puffs of rescue medication per day on more than 2 consecutive days in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2. In case of an asthma deterioration occurring in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2, the visit must be postponed.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01277523

  Show 69 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: NCT01277523     History of Changes
Other Study ID Numbers: 205.456, 2010-021778-13
Study First Received: January 13, 2011
Last Updated: April 2, 2014
Health Authority: Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica
Australia: Human Research Ethics Committee
Bulgaria: Bulgarian Drug Agency
Germany: Federal Institute for Drugs and Medical Devices
Guatemala: Ministry of Public Health and Social Assistance
Hungary: National Institute of Pharmacy
Israel: Israeli Health Ministry Pharmaceutical Administration
Latvia: State Agency of Medicines
Mexico: Federal Commission for Sanitary Risks Protection
Philippines: Bureau of Food and Drugs
Portugal: National Pharmacy and Medicines Institute
South Africa: Medicines Control Council
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 17, 2014