Comparison of Combination Therapy: Montelukast and Inhaled Steroid on Exercise Induced Bronchoconstriction

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
McMaster University
ClinicalTrials.gov Identifier:
NCT00462592
First received: April 18, 2007
Last updated: October 20, 2009
Last verified: October 2009
  Purpose

The purpose of this study is to compare the effects of 2 weeks therapy of montelukast, budesonide, their combination on exercise induced bronchoconstriction (EIB) and airway inflammation in children and young adults, not on regular controller therapy.

Inhaled corticosteroids (ICS) are potent anti-inflammatory agents, which are effective in controlling and improving all aspects of asthma including the attenuation of EIB. However, the effect of ICS monotherapy on EIB is comparable if not inferior to the effect of CysLTs modifiers alone. This may be due to the lack of effect of ICS on the CysLT pathway. As a consequence, the investigators hypothesize that the combination of ICS and CysLT modifiers will offer a greater protection against EIB than either therapy alone. The different classes of drugs may act on complementary pathways believed to be important in the pathophysiology of EIB.


Condition Intervention Phase
Asthma
Drug: budesonide
Drug: montelukast
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised Double Blind, Placebo Controlled 4-way Cross Over Study Comparing Montelukast, Inhaled Budesonide and Their Combination on Exercise-induced Bronchoconstriction

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • The magnitude of protection and the number of subjects with ≥50% protection (considered to be clinically relevant) following treatment [ Time Frame: Before and after 2 weeks of treatment in each 4 arm ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in sputum cell counts and fluid phase inflammatory mediators [ Time Frame: Before and after 2 weeks of treatment in each 4 arm ] [ Designated as safety issue: No ]
  • Change in baseline exhaled nitric oxide (eNO) and response to exercise challenge [ Time Frame: Before and after 2 weeks of treatment in each 4 arm ] [ Designated as safety issue: No ]
  • Change in EBC (exhaled breath condensate) inflammatory mediators from baseline [ Time Frame: Before and after 2 weeks of treatment in each 4 arm ] [ Designated as safety issue: No ]
  • The change in exercise induced maximal percent fall in FEV1 (maxFEV1%) and area under the curve (AUC0-30) relative to pre-exercise FEV1 up to 30 minutes following exercise challenge [ Time Frame: Before and after 2 weeks of treatment in each 4 arm ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: March 2007
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
montelukast - montelukast 5 mg ( < 15 years) or 10 mg (and matching placebo)will be taken 1 tab in the evening
Drug: montelukast
montelukast 5 mg ( < 15 years) or 10 mg (and matching placebo)will be taken 1 tab in the evening
Other Name: montelukast (Singulair)
Other: placebo
placebo
Other Name: placebo
Active Comparator: 2
budesonide - inhaled budesonide turbuhaler 200ug (& matching placebo) taken 1 puff morning & 1 puff evening.
Drug: budesonide
inhaled budesonide turbuhaler 200ug taken 1 puff morning & 1 puff evening.
Other Name: budesonide (Pulmicort)
Other: placebo
placebo
Other Name: placebo
Placebo Comparator: 3
placebo
Other: placebo
placebo
Other Name: placebo
Active Comparator: 4
montelukast budesonide combination - montelukast 5mg ( < 15 years) or 10 mg (& matching placebo)will be taken 1 tab in the evening together with inhaled budesonide turbuhaler 200 ug (& matching placebo) taken 1 puff morning & 1 puff evening.
Drug: budesonide
inhaled budesonide turbuhaler 200ug taken 1 puff morning & 1 puff evening.
Other Name: budesonide (Pulmicort)
Drug: montelukast
montelukast 5 mg ( < 15 years) or 10 mg (and matching placebo)will be taken 1 tab in the evening
Other Name: montelukast (Singulair)
Other: placebo
placebo
Other Name: placebo

Detailed Description:

The study will be a 2 centre randomised, double blind, placebo controlled 4-way cross over study comparing montelukast, budesonide and their combination on exercise-induced bronchoconstriction (EIB). Subjects with stable mild to moderate asthma, between the ages of 8-35 years, not on controller asthma therapy will be screened. A maxFEV1% ≥15% following a standardized dry air exercise challenge at screening (SC) and following a 1 week run-in (V-1) is required to qualify. Once qualified, subjects will return the following day (V0) for a skin prick test and a methacholine inhalation test before being randomised to 1 of 4 treatment sequences. Each treatment will be given for a total of 14 days with a 4 weeks washout. During each period, subjects will attend the laboratory on 2 occasions, at the beginning and end of each period. Baseline spirometry; eNO; EBC will be performed, followed by an exercise challenge with serial FEV1 and eNO measurements up to 30 minutes post exercise and post-exercise EBC and sputum induction at each evaluation visit. There will be a total of 10 visits and the duration of study will be approximately 148 days (21 weeks). All visits will be scheduled within 2 hours of the post-run visit (V1) and at least 8 hours after the last dose of trial medications.

Investigational Product, Dose and Administration:

Montelukast 5mg (<15 years) or 10mg (and matching placebo) will be taken 1 tablet in the evening together with inhaled budesonide turbuhalers 200ug (and matching placebo) taken 1 puff in the morning and 1 puff in the evening.

Efficacy on EIB:

The changes between pre and post treatment exercise-induced maxFEV1% and area under the curve (AUC0-30) will be compared between the 4 periods. MaxFEV1% will be calculated as pre-exercise FEV1 minus post exercise lowest FEV1 divided by pre-exercise FEV1 multiplied by 100; AUC will be calculated using the trapezoidal rule. The protection provided by the active treatments will be defined as the pre-treatment maxFEV1% minus post-treatment maxFEV1% divided by pre-treatment maxFEV1% x 100. The proportions of subjects attaining ≥50% protection will be compared between the 4 arms.

Efficacy on eNO and inflammatory parameters measured in sputum and EBC Changes in % and absolute counts of sputum differential cells, eNO and inflammatory mediators (in EBC/ sputum) at baseline and in response to exercise will be compared between the 4 arms.

  Eligibility

Ages Eligible for Study:   8 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or females ages 8-35 years with stable mild-to-moderate asthma (ATS criteria) not on regular controller therapy
  • Prebronchodilator FEV1 predicted ≥ 70%
  • No other medical co-morbidity
  • Demonstrate maxFEV1% ≥15% on exercise challenge at screening and 1 week post run-in.

Exclusion Criteria:

  • Asthma exacerbations or respiratory infection within 4 weeks of screening
  • Recent use of inhaled or systemic steroids
  • Immunosuppressives
  • Antihistamines, NSAIDs and investigational drugs within 30 days
  • Unable to reliably perform spirometry and exercise challenge
  • Current or ex-smokers ≥ 10 pack-years and less than 1 month abstinence
  • Contra-indications to inhaled steroids or montelukast use.
  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: NCT00462592

Locations
Canada, Ontario
Hamilton Health Sciences-McMaster University
Hamilton, Ontario, Canada, L8N 3Z5
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
Hamilton Health Sciences Corporation
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Paul O'Byrne, MD McMaster University
  More Information

No publications provided

Responsible Party: Paul O'Byrne, McMaster University
ClinicalTrials.gov Identifier: NCT00462592     History of Changes
Other Study ID Numbers: monbud8035
Study First Received: April 18, 2007
Last Updated: October 20, 2009
Health Authority: Canada: Health Canada

Keywords provided by McMaster University:
exercise-induced bronchoconstriction (EIB)
airway inflammation

Additional relevant MeSH terms:
Budesonide
Montelukast
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Autonomic Agents
Bronchodilator Agents
Glucocorticoids
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Leukotriene Antagonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014