Asthma
Conditions
Brief summary
This study assesses inhaled corticosteroid plus montelukast compared with inhaled corticosteroid therapy alone for treatment of patients with chronic asthma.
Detailed description
During this study, all patients will receive mometasone (powder, 220 mcg once-daily, for approximately 6 weeks). In a crossover manner, eligible patients will also receive montelukast (powder, 1 mg once-daily, for approximately 2 weeks) followed by placebo; or will receive placebo followed by montelukast. The order of when each of these 2 treatments are added to the mometasone will be randomized.
Interventions
mometasone (inhalation powder, 220 mcg once-daily, for approximately 6 weeks)
montelukast (inhalation powder, 1 mg once-daily, for approximately 2 weeks)
DRUGComparator: placebo (unspecified)
Placebo (Placebo once-daily, for approximately 2 weeks)
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
15 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Patient has decreased breathing capacity (when not taking asthma medicine) that improves after taking a fast-acting asthma inhaler * Within one month of the first study visit, patient has been treated with a fast-acting asthma inhaler, and may be treated with a corticosteroid inhaler or an inhaler that combines a corticosteroid plus a bronchodilator
Exclusion criteria
* Patient is hypersensitive to inhaled beta-agonists, corticosteroids, leukotriene antagonists, or any of their components * Has required an oral corticosteroid rescue for worsening asthma during the screening period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FEV1 (Forced Expiratory Volume; Volume of Air That is Exhaled During the First Second of a Forced Exhalation) | Baseline and 2 weeks | To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on bronchodilation assessed by average change from baseline in FEV1 over the 2 week treatment period; measurements taken at 1 and 2 weeks contributed to the average. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Daytime Asthma Symptom Score | Baseline and 2 weeks | To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on asthma symptoms assessed by average change from baseline in daytime asthma symptom score (which could range from 0 \[best\] to 6 \[worst\]) over the 2 week treatment period; measurements taken at 1 and 2 weeks contributed to the average. |
| Change From Baseline in Nighttime Asthma Symptom Score | Baseline and 2 weeks | To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on asthma symptoms assessed by average change from baseline in nighttime asthma symptom score (which could range from 0 \[best\] to 3 \[worst\]) over the 2 week treatment period; measurements taken at 1 and 2 weeks contributed to the average. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Daily β-agonist Use | Baseline and 2 weeks | To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on as-needed β-agonist use assessed by average change from baseline in total daily β-agonist use over the 2 week treatment period; measurements taken at 1 and 2 weeks contributed to the average. |
| Change From Baseline in Total Peripheral Blood Eosinophils | Baseline and 2 weeks | To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on change from baseline in total peripheral blood eosinophils during the 2 week treatment period. |
| Percentage of Days With Asthma Control | 2 weeks | To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on asthma control assessed by average percentage of days with asthma control over the 2 week treatment period; measurements taken at 1 and 2 weeks contributed to the average. |
| Percentage of Days With Asthma Exacerbations | 2 Weeks | To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on worsening of asthma assessed by percentage of days with asthma exacerbations during the 2 week treatment period. |
Participant flow
Recruitment details
Patients were recruited from 25 centers worldwide. Patient screening began 05-May-2008 and the first patient was randomized on 29-May-2008. The last patient's last visit was completed on 16-Feb-2009.
Pre-assignment details
278 participants were screened; 144 were excluded. Randomized patients met the following criteria: FEV1 (Forced expiratory volume in one second) 50-80% predicted while withholding short-acting beta agonist (SABA) and reversibility of airway obstruction \>12% following SABA documented on at least two of the following visits: Visits 1, 2, and 3.
Participants by arm
| Arm | Count |
|---|---|
| Montelukast + Mometasone Then Placebo + Mometasone Patients were randomized to receive montelukast 1 mg (milligram) and open-label mometasone 220 mcg (micrograms) once daily by inhalation in the first intervention; and placebo for montelukast and open-label mometasone 220 mcg once daily by inhalation in the second intervention (after washout). During washout, patients received open-label inhaled mometasone 220 mcg and single-blind placebo for montelukast once daily by inhalation. | 66 |
| Placebo + Mometasone Then Montelukast + Mometasone Patients were randomized to receive placebo for montelukast and open-label mometasone 220 mcg once daily by inhalation in the first intervention; and montelukast 1 mg and open-label mometasone 220 mcg once daily by inhalation in the second intervention (after washout). During washout, patients received open-label inhaled mometasone 220 mcg and single-blind placebo for montelukast once daily by inhalation. | 68 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Lost to Follow-up | 1 | 0 |
| First Intervention | Protocol Violation | 1 | 0 |
| First Intervention | Randomized did not start treatment | 1 | 1 |
| First Intervention | Withdrawal by Subject | 1 | 0 |
| Second Intervention | Adverse Event | 1 | 0 |
| Second Intervention | Death | 0 | 1 |
| Washout Period of 1 Week | Lost to Follow-up | 0 | 1 |
| Washout Period of 1 Week | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Montelukast + Mometasone Then Placebo + Mometasone | Placebo + Mometasone Then Montelukast + Mometasone | Total |
|---|---|---|---|
| Age, Continuous | 39.2 years STANDARD_DEVIATION 15.5 | 42.6 years STANDARD_DEVIATION 14.8 | 40.9 years STANDARD_DEVIATION 15.2 |
| Daytime Asthma Symptom Score (0 [best] to 6 [worst] Point Scale) | 2.04 Units on a Scale STANDARD_DEVIATION 0.9 | 2.18 Units on a Scale STANDARD_DEVIATION 0.81 | 2.11 Units on a Scale STANDARD_DEVIATION 0.85 |
| FEV1 (Forced Expiratory Volume in One Second) | 2.14 L (Liter) STANDARD_DEVIATION 0.67 | 2.18 L (Liter) STANDARD_DEVIATION 0.55 | 2.16 L (Liter) STANDARD_DEVIATION 0.61 |
| Nighttime Asthma Symptom Score (0 [best] to 3 [worst] Point Scale) | 0.51 Units on a Scale STANDARD_DEVIATION 0.53 | 0.46 Units on a Scale STANDARD_DEVIATION 0.48 | 0.49 Units on a Scale STANDARD_DEVIATION 0.5 |
| Sex: Female, Male Female | 37 Participants | 32 Participants | 69 Participants |
| Sex: Female, Male Male | 29 Participants | 36 Participants | 65 Participants |
| Total Daily Beta-Agonist Use | 3.52 Puffs STANDARD_DEVIATION 2.49 | 3.55 Puffs STANDARD_DEVIATION 2.19 | 3.53 Puffs STANDARD_DEVIATION 2.34 |
| Total Peripheral Blood Eosinophils | 0.46 10^3/microliters STANDARD_DEVIATION 0.39 | 0.38 10^3/microliters STANDARD_DEVIATION 0.31 | 0.42 10^3/microliters STANDARD_DEVIATION 0.35 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 130 | 24 / 129 |
| serious Total, serious adverse events | 1 / 130 | 1 / 129 |
Outcome results
Primary
Change From Baseline in FEV1 (Forced Expiratory Volume; Volume of Air That is Exhaled During the First Second of a Forced Exhalation)
To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on bronchodilation assessed by average change from baseline in FEV1 over the 2 week treatment period; measurements taken at 1 and 2 weeks contributed to the average.
Time frame: Baseline and 2 weeks
Population: The analysis was based on the Full analysis set (FAS) population which included all randomized patients who took at least one dose of blinded post randomization study drug (inhaled montelukast or matching placebo) and had a measurement for analysis available in at least one treatment period of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast + Mometasone | Change From Baseline in FEV1 (Forced Expiratory Volume; Volume of Air That is Exhaled During the First Second of a Forced Exhalation) | 0.22 L (Liter) |
| Placebo + Mometasone | Change From Baseline in FEV1 (Forced Expiratory Volume; Volume of Air That is Exhaled During the First Second of a Forced Exhalation) | 0.17 L (Liter) |
p-value: 0.03395% CI: [0, 0.09]Mixed Models Analysis
Secondary
Change From Baseline in Daytime Asthma Symptom Score
To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on asthma symptoms assessed by average change from baseline in daytime asthma symptom score (which could range from 0 \[best\] to 6 \[worst\]) over the 2 week treatment period; measurements taken at 1 and 2 weeks contributed to the average.
Time frame: Baseline and 2 weeks
Population: The analysis was based on the FAS population which included all randomized patients who took at least one dose of blinded post randomization study drug (inhaled montelukast or matching placebo) and had a measurement for analysis available in at least one treatment period of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast + Mometasone | Change From Baseline in Daytime Asthma Symptom Score | -0.39 Units on a Scale |
| Placebo + Mometasone | Change From Baseline in Daytime Asthma Symptom Score | -0.24 Units on a Scale |
p-value: 0.00595% CI: [-0.26, -0.05]Mixed Models Analysis
Secondary
Change From Baseline in Nighttime Asthma Symptom Score
To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on asthma symptoms assessed by average change from baseline in nighttime asthma symptom score (which could range from 0 \[best\] to 3 \[worst\]) over the 2 week treatment period; measurements taken at 1 and 2 weeks contributed to the average.
Time frame: Baseline and 2 weeks
Population: The analysis was based on a subset of the FAS population which included all randomized patients with nighttime symptoms at baseline (score\>0), who took at least one dose of blinded post randomization study drug (inhaled montelukast or matching placebo) and had a measurement for analysis available in at least one treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast + Mometasone | Change From Baseline in Nighttime Asthma Symptom Score | -0.28 Units on a Scale |
| Placebo + Mometasone | Change From Baseline in Nighttime Asthma Symptom Score | -0.18 Units on a Scale |
p-value: 0.01595% CI: [-0.17, -0.02]Mixed Models Analysis
Post Hoc
Change From Baseline in FEV1 (Forced Expiratory Volume; Volume of Air That is Exhaled During the First Second of a Forced Exhalation) in Patients Who Met Lung Function Eligibility Criteria Specifically at the Randomization Visit.
To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on bronchodilation assessed by average change from baseline in FEV1 over the 2 week treatment period in patients who met lung function eligibility criteria at randomization; measurements taken at 1 and 2 weeks contributed to average.
Time frame: Baseline and 2 Weeks
Population: The analysis was based on a subset of the Full analysis set (FAS) population which included all randomized patients who took at least one dose of blinded post randomization study drug, had a measurement for analysis available in at least one treatment period and met lung function eligibility criteria specifically at the randomization visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast + Mometasone | Change From Baseline in FEV1 (Forced Expiratory Volume; Volume of Air That is Exhaled During the First Second of a Forced Exhalation) in Patients Who Met Lung Function Eligibility Criteria Specifically at the Randomization Visit. | 0.27 L (Liter) |
| Placebo + Mometasone | Change From Baseline in FEV1 (Forced Expiratory Volume; Volume of Air That is Exhaled During the First Second of a Forced Exhalation) in Patients Who Met Lung Function Eligibility Criteria Specifically at the Randomization Visit. | 0.19 L (Liter) |
p-value: 0.00295% CI: [0.03, 0.13]Mixed Models Analysis
Other Pre-specified
Change From Baseline in Total Daily β-agonist Use
To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on as-needed β-agonist use assessed by average change from baseline in total daily β-agonist use over the 2 week treatment period; measurements taken at 1 and 2 weeks contributed to the average.
Time frame: Baseline and 2 weeks
Population: The analysis was based on the FAS population which included all randomized patients who took at least one dose of blinded post randomization study drug (inhaled montelukast or matching placebo) and had a measurement for analysis available in at least one treatment period of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast + Mometasone | Change From Baseline in Total Daily β-agonist Use | -0.87 Puffs |
| Placebo + Mometasone | Change From Baseline in Total Daily β-agonist Use | -0.27 Puffs |
p-value: 0.07395% CI: [-1.26, 0.06]Mixed Models Analysis
Other Pre-specified
Change From Baseline in Total Peripheral Blood Eosinophils
To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on change from baseline in total peripheral blood eosinophils during the 2 week treatment period.
Time frame: Baseline and 2 weeks
Population: The analysis was based on the FAS population which included all randomized patients who took at least one dose of blinded post randomization study drug (inhaled montelukast or matching placebo) and had a measurement for analysis available in at least one treatment period of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast + Mometasone | Change From Baseline in Total Peripheral Blood Eosinophils | -0.05 10^3/microliter |
| Placebo + Mometasone | Change From Baseline in Total Peripheral Blood Eosinophils | 0.02 10^3/microliter |
p-value: 0.01395% CI: [-0.12, -0.01]Mixed Models Analysis
Other Pre-specified
Percentage of Days With Asthma Control
To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on asthma control assessed by average percentage of days with asthma control over the 2 week treatment period; measurements taken at 1 and 2 weeks contributed to the average.
Time frame: 2 weeks
Population: The analysis was based on the FAS population which included all randomized patients who took at least one dose of blinded post randomization study drug (inhaled montelukast or matching placebo) and had a measurement for analysis available in at least one treatment period of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast + Mometasone | Percentage of Days With Asthma Control | 35.13 Percentage of Days |
| Placebo + Mometasone | Percentage of Days With Asthma Control | 29.04 Percentage of Days |
p-value: 0.00495% CI: [1.94, 10.23]Mixed Models Analysis
Other Pre-specified
Percentage of Days With Asthma Exacerbations
To determine the effect of 2 weeks of treatment with inhaled montelukast plus mometasone and mometasone alone on worsening of asthma assessed by percentage of days with asthma exacerbations during the 2 week treatment period.
Time frame: 2 Weeks
Population: The analysis was based on the Completers Set population which included all randomized patients who took a dose of blinded post randomization study drug (inhaled montelukast or matching placebo) in both treatment periods and had a measurement for analysis available in both treatment periods of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast + Mometasone | Percentage of Days With Asthma Exacerbations | 9.71 Percentage of Days |
| Placebo + Mometasone | Percentage of Days With Asthma Exacerbations | 15.14 Percentage of Days |
p-value: <=0.00195% CI: [-8.67, -2.19]ANCOVA