AsthmaPhase 3NCT00462592
Comparison of Combination Therapy: Montelukast and Inhaled Steroid on Exercise Induced Bronchoconstriction
A Phase 3 study testing budesonide and montelukast in people with Asthma, run by Hamilton Health Sciences Corporation at 2 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 to 35 years
- Conditions the study is for
- Asthma
- What is being tested?
- budesonide and montelukast
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 2 sitesCanada
- Study dates
- Mar 2007to Jun 2009
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Hamilton Health Sciences-McMaster University
Hamilton, Ontario, L8N 3Z5
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
About this study
Official title: A Randomised Double Blind, Placebo Controlled 4-way Cross Over Study Comparing Montelukast, Inhaled Budesonide and Their Combination on Exercise-induced Bronchoconstriction
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.
Read the 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.
- Conditions
- Asthma
- Being tested
- budesonide, montelukast, placebo
- Keywords
- exercise-induced bronchoconstriction (EIB), airway inflammation
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
budesonideDrug
Also called budesonide (Pulmicort)
inhaled budesonide turbuhaler 200ug taken 1 puff morning \& 1 puff evening.
montelukastDrug
Also called montelukast (Singulair)
montelukast 5 mg ( < 15 years) or 10 mg (and matching placebo)will be taken 1 tab in the evening
placeboOther
placebo
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | montelukast - montelukast 5 mg ( < 15 years) or 10 mg (and matching placebo)will be taken 1 tab in the evening Receives: Drug: montelukast; Other: placebo |
| 2 | Active comparator | budesonide - inhaled budesonide turbuhaler 200ug (\& matching placebo) taken 1 puff morning \& 1 puff evening. Receives: Drug: budesonide; Other: placebo |
| 3 | Placebo comparator | placebo Receives: Other: placebo |
| 4 | Active comparator | 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. Receives: Drug: budesonide; Drug: montelukast; Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The magnitude of protection and the number of subjects with ≥50% protection (considered to be clinically relevant) following treatment
Measured: Before and after 2 weeks of treatment in each 4 arm
Secondary outcomes (4)
Change in sputum cell counts and fluid phase inflammatory mediators
Measured: Before and after 2 weeks of treatment in each 4 arm
Change in baseline exhaled nitric oxide (eNO) and response to exercise challenge
Measured: Before and after 2 weeks of treatment in each 4 arm
Change in EBC (exhaled breath condensate) inflammatory mediators from baseline
Measured: Before and after 2 weeks of treatment in each 4 arm
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
Measured: Before and after 2 weeks of treatment in each 4 arm
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2007 (estimated)
- Study startMar 2007
- Primary completionJun 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hamilton Health Sciences Corporation
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Investigators
- Paul O'Byrne, MD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00462592
- Sponsor's protocol ID
- monbud8035
- Status last verified
- Oct 2009
- First submitted
- 18 Apr 2007
- Last updated
- 21 Oct 2009
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Double Blind, Placebo Controlled 4-way Cross Over Study Comparing Montelukast, Inhaled Budesonide and Their Combination on Exercise-induced Bronchoconstriction
- ClinicalTrials.gov ID
- NCT00462592
- Acronym / sponsor ID
- monbud8035
- Conditions
- Asthma
- Keywords
- exercise-induced bronchoconstriction (EIB), airway inflammation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Hamilton Health Sciences CorporationUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Mar 2007
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 19 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: montelukast, Other: placebomontelukast - montelukast 5 mg ( < 15 years) or 10 mg (and matching placebo)will be taken 1 tab in the evening |
| 2 | Active comparator | Drug: budesonide, Other: placebobudesonide - inhaled budesonide turbuhaler 200ug (\& matching placebo) taken 1 puff morning \& 1 puff evening. |
| 3 | Placebo comparator | Other: placeboplacebo |
| 4 | Active comparator | Drug: budesonide, Drug: montelukast, Other: placebomontelukast 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. |
Who may qualify
- Ages
- 8 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| budesonideAlso: budesonide (Pulmicort)inhaled budesonide turbuhaler 200ug taken 1 puff morning \& 1 puff evening. | Drug | 2, 4 |
| montelukastAlso: montelukast (Singulair)montelukast 5 mg ( < 15 years) or 10 mg (and matching placebo)will be taken 1 tab in the evening | Drug | 1, 4 |
| placeboplacebo | Other | 1, 2, 3, 4 |
Primary outcome
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
4 secondary outcomes
Change in sputum cell counts and fluid phase inflammatory mediators
Time frame: Before and after 2 weeks of treatment in each 4 arm
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
Change in EBC (exhaled breath condensate) inflammatory mediators from baseline
Time frame: Before and after 2 weeks of treatment in each 4 arm
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul O'Byrne, MD principal investigator
McMaster University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing budesonide and montelukast in people with Asthma, run by Hamilton Health Sciences Corporation at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2009.