Asthma, Exercise-Induced
Conditions
Brief summary
The purpose of this study is to determine the effect of an approved medication being studied in support of a new approach in the prevention of exercise-induced asthma (a worsening of asthma caused by exercise, also known as exercise-induced bronchospasm), in patients who have a history of worsening asthma after exercise.
Interventions
Montelukast 10 mg tablet administered orally as a single witnessed dose before exercise challenge
DRUGComparator: Placebo
Placebo tablet administered orally as a single witnessed dose before exercise challenge
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
15 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Patients with mild-to-moderate asthma
Exclusion criteria
* Medical history of a lung disorder (other than asthma) or a recent upper respiratory tract infection * Patient is, other than asthma, not in good, stable health * The Primary Investigator will evaluate whether there are other reasons why the patient may not participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Percent Fall in FEV1 After Exercise Challenge at 2 Hours Post-dose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB) | Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 2 hours after a single oral dose | In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (2 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 12 Hours Postdose | 0-90 minutes after the exercise challenge performed at 12 hours postdose | — |
| Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose | 0-90 minutes after the exercise challenge performed at 24 hours postdose | — |
| Maximum Percent Fall in FEV1 After Exercise Challenge at 12 Hours Postdose Compared With Pre-exercise Baseline in Patients With EIB | Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 12 hours after a single oral dose | In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (12 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge. |
| Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Postdose Compared With Pre-exercise Baseline in Patients With EIB | Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 24 hours after a single oral dose | In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (24 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge. |
| Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 2 Hours Postdose | Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 2 hours postdose | The measure included only the area below the pre-exercise baseline. |
| Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose | 0-90 minutes after the exercise challenge performed at 2 hours postdose | — |
| Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) at 24 Hours Postdose | Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 24 hours postdose | The measure included only the area below the pre-exercise baseline. |
| Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 2 Hours Postdose | Exercise challenge at 2 hours postdose | The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time. |
| Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 12 Hours Postdose | Exercise challenge at 12 hours postdose | The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time. |
| Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 24 Hours Postdose | Exercise challenge at 24 hours postdose | The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time. |
| Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 12 Hours Postdose | Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 12 hours postdose | The measure included only the area below the pre-exercise baseline. |
Participant flow
Recruitment details
Patients were randomized at 8 sites (7 in the US and 1 in Peru). Primary therapy period: May to October 2004.
Pre-assignment details
Patients who required excluded medications, or did not meet FEV1 criteria during the prestudy period were excluded from randomization. Patients who required a β-agonist after the exercise challenge and did not meet FEV1 criteria within 30 minutes of treatment were also excluded.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Population All randomized patients | 62 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period I | Lost to Follow-up | 1 | 2 |
| Treatment Period I | Other | 0 | 1 |
| Treatment Period I | Protocol Violation | 2 | 0 |
| Treatment Period I | Withdrawal by Subject | 2 | 0 |
| Treatment Period II | Other | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Study Population |
|---|---|
| Age, Continuous | 24.4 years STANDARD_DEVIATION 6.9 |
| AUC for percent change from pre-exercise measurement FEV1 in L 0-60 mins after exercise challenge | 815.27 (percent change) *minutes STANDARD_DEVIATION 516.83 |
| Maximum percent fall in Forced Expiratory Volume in 1 second (FEV1) post-exercise challenge | 26.86 percent change from pre-exercise measure STANDARD_DEVIATION 7.04 |
| Need for β-agonist rescue medication following exercise challenge No | 47 Participants |
| Need for β-agonist rescue medication following exercise challenge Yes | 15 Participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 33 Participants |
| Time to recovery from maximal percent fall | 44.73 Minutes STANDARD_DEVIATION 32.23 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 58 | 3 / 57 |
| serious Total, serious adverse events | 0 / 58 | 0 / 57 |
Outcome results
Primary
Maximum Percent Fall in FEV1 After Exercise Challenge at 2 Hours Post-dose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB)
In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (2 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge.
Time frame: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 2 hours after a single oral dose
Population: The primary efficacy analysis used the modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Percent Fall in FEV1 After Exercise Challenge at 2 Hours Post-dose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB) | 17.50 Percent Change | Standard Deviation 13.82 |
| Montelukast 10 mg | Maximum Percent Fall in FEV1 After Exercise Challenge at 2 Hours Post-dose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB) | 11.70 Percent Change | Standard Deviation 10.8 |
Secondary
Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 12 Hours Postdose
The measure included only the area below the pre-exercise baseline.
Time frame: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 12 hours postdose
Population: The secondary efficacy analysis used a MITT approach. If a patient received β-agonist rescue medication during the 60 minutes following exercise challenge, then the last pre-rescue FEV1 measurement was carried forward to 60 minutes. Patients with data from only one period were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 12 Hours Postdose | 314.0 (percent change) *minutes | Standard Deviation 417.7 |
| Montelukast 10 mg | Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 12 Hours Postdose | 241.7 (percent change) *minutes | Standard Deviation 545.9 |
Secondary
Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) at 24 Hours Postdose
The measure included only the area below the pre-exercise baseline.
Time frame: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 24 hours postdose
Population: The secondary efficacy analysis was an MITT approach. If a patient received β-agonist rescue medication during the 60 minutes following exercise challenge, then the last pre-rescue FEV1 measurement was carried forward to 60 minutes. Patients with data from only one period were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) at 24 Hours Postdose | 269.6 (percent change) *minutes | Standard Deviation 507.8 |
| Montelukast 10 mg | Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) at 24 Hours Postdose | 223.1 (percent change) *minutes | Standard Deviation 527.1 |
Secondary
Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 2 Hours Postdose
The measure included only the area below the pre-exercise baseline.
Time frame: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 2 hours postdose
Population: The secondary efficacy analysis used a MITT approach. If a patient received β-agonist rescue medication during the 60 minutes following exercise challenge, then the last pre-rescue FEV1 measurement was carried forward to 60 minutes. Patients with data from only one period were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 2 Hours Postdose | 582.6 (percent change) *minutes | Standard Deviation 759.1 |
| Montelukast 10 mg | Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 2 Hours Postdose | 284.7 (percent change) *minutes | Standard Deviation 426.9 |
Secondary
Maximum Percent Fall in FEV1 After Exercise Challenge at 12 Hours Postdose Compared With Pre-exercise Baseline in Patients With EIB
In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (12 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge.
Time frame: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 12 hours after a single oral dose
Population: The primary efficacy analysis used the modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Percent Fall in FEV1 After Exercise Challenge at 12 Hours Postdose Compared With Pre-exercise Baseline in Patients With EIB | 11.73 Percent Change | Standard Deviation 11.64 |
| Montelukast 10 mg | Maximum Percent Fall in FEV1 After Exercise Challenge at 12 Hours Postdose Compared With Pre-exercise Baseline in Patients With EIB | 9.87 Percent Change | Standard Deviation 11.43 |
Secondary
Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Postdose Compared With Pre-exercise Baseline in Patients With EIB
In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (24 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge.
Time frame: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 24 hours after a single oral dose
Population: The primary efficacy analysis used the modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Postdose Compared With Pre-exercise Baseline in Patients With EIB | 10.69 Percent Change | Standard Deviation 12.31 |
| Montelukast 10 mg | Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Postdose Compared With Pre-exercise Baseline in Patients With EIB | 7.95 Percent Change | Standard Deviation 10.8 |
Secondary
Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 12 Hours Postdose
Time frame: 0-90 minutes after the exercise challenge performed at 12 hours postdose
Population: The secondary efficacy analysis used a modified~intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 12 Hours Postdose | Patients requiring rescue medication | 4 Participants |
| Placebo | Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 12 Hours Postdose | Patients not requiring rescue medication | 48 Participants |
| Montelukast 10 mg | Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 12 Hours Postdose | Patients requiring rescue medication | 2 Participants |
| Montelukast 10 mg | Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 12 Hours Postdose | Patients not requiring rescue medication | 50 Participants |
Secondary
Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose
Time frame: 0-90 minutes after the exercise challenge performed at 24 hours postdose
Population: The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose | Patients requiring rescue medication | 2 Participants |
| Placebo | Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose | Patients not requiring rescue medication | 50 Participants |
| Montelukast 10 mg | Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose | Patients requiring rescue medication | 2 Participants |
| Montelukast 10 mg | Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose | Patients not requiring rescue medication | 50 Participants |
Secondary
Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose
Time frame: 0-90 minutes after the exercise challenge performed at 2 hours postdose
Population: The secondary efficacy analysis used a modified~intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose | Patients requiring rescue medication | 7 Participants |
| Placebo | Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose | Patients not requiring rescue medication | 47 Participants |
| Montelukast 10 mg | Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose | Patients requiring rescue medication | 2 Participants |
| Montelukast 10 mg | Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose | Patients not requiring rescue medication | 52 Participants |
Secondary
Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 12 Hours Postdose
The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.
Time frame: Exercise challenge at 12 hours postdose
Population: The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 12 Hours Postdose | 23.40 Minutes | Standard Deviation 32.2 |
| Montelukast 10 mg | Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 12 Hours Postdose | 9.42 Minutes | Standard Deviation 18.27 |
Secondary
Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 24 Hours Postdose
The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.
Time frame: Exercise challenge at 24 hours postdose
Population: The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 24 Hours Postdose | 13.81 Minutes | Standard Deviation 22.8 |
| Montelukast 10 mg | Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 24 Hours Postdose | 9.47 Minutes | Standard Deviation 19.52 |
Secondary
Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 2 Hours Postdose
The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.
Time frame: Exercise challenge at 2 hours postdose
Population: The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 2 Hours Postdose | 34.23 Minutes | Standard Deviation 36.01 |
| Montelukast 10 mg | Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 2 Hours Postdose | 15.87 Minutes | Standard Deviation 25.29 |