Comparison of Combination Therapy: Montelukast and Inhaled Steroid on Exercise Induced Bronchoconstriction
Condition: Asthma
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

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.
    

Intervention name(s): budesonide; montelukast; placebo
Intervention type(s): Drug; Drug; Other
Intervention description(s): inhaled budesonide turbuhaler 200ug taken 1 puff morning & 1 puff evening.; montelukast 5 mg ( < 15 years) or 10 mg (and matching placebo)will be taken 1 tab in the evening; placebo
Other intervention name(s): budesonide (Pulmicort); montelukast (Singulair)
Intervention MeSH terms: Budesonide; Montelukast
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: exercise-induced bronchoconstriction (EIB); airway inflammation