Asthma
Conditions
Keywords
chronic asthma
Brief summary
This study will investigate the additive effect of montelukast (MK0476) taken along with inhaled beclomethasone versus inhaled beclomethasone alone.
Interventions
DRUGmontelukast sodium
10 mg tablet taken once daily at bedtime for 16 weeks
DRUGbeclomethasone
200 ug inhaled, taken twice daily for 16 weeks
DRUGPlacebo inhaler
placebo inhaler taken twice daily for 16 weeks
DRUGplacebo tablet
placebo tablet taken once daily at bedtime for 16 weeks
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
15 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Female patients tested negative for pregnancy and agreed to use appropriate contraceptives through out the study * Patient was a nonsmoker * Patient was in good general health (except for asthma)
Exclusion criteria
* Patient was hospitalized * Patient was female who was less than 8 weeks postpartum or breast feeding * Patient planned to move or vacation away during the study * Patient had major surgery within 4 weeks the past 4 weeks * Patient has donated blood or participated in a clinical trial within the past 4 weeks * Patient was a regular user or recent abuser of alcohol or illicit drugs * Patient was 40% over or under normal weight for height
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) in Patients With Chronic Asthma | Baseline & over 16 weeks for the Beclomethasone (Beclo) and Montelukast (MK) + Beclo groups and over last 10 weeks for the Placebo and MK groups | Mean percent change from baseline in FEV1 in patients with chronic asthma averaged over 16 weeks for the Beclo and MK+ Beclo groups and averaged over last 10 weeks for the Placebo and MK groups |
| Mean Change From Baseline in Daytime Symptom Score on the Daytime Asthma Symptoms Diary in Patients With Chronic Asthma | Baseline & over 16 weeks for the Beclo and MK + Beclo groups and over last 10 weeks for the Placebo and MK groups | The daily daytime symptom score was determined by averaging the daily scores (the patient scored his/her symptoms \[from 0 (best) to 6 (worst)\] on a daily basis.) for the four questions on the Daytime Asthma Symptoms Diary. The average daytime symptom score for the visit was determined by averaging the daily symptom scores over all days between two consecutive visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in Total Daily Beta-agonist Medication Use | Baseline & over 16 weeks for the Beclo and MK + Beclo groups and over last 10 weeks for the Placebo and MK groups | Beta-agonist medication use from the daytime and overnight asthma symptoms diaries for each 24-hour period was added to determine the daily total number of puffs used. The average daily number of puffs for the visit was determined as the average daily number of puffs over all days between consecutive visits. |
| Mean Change From Baseline in Morning Peak Flow Rate (PEFR) in Patients With Chronic Asthma | Baseline & over 16 weeks for the Beclo and MK + Beclo groups and over last 10 weeks for the Placebo and MK groups | Morning PEFR was measured in triplicate immediately upon arising before taking any medication and the best value recorded on the overnight asthma symptoms diary. The mean morning PEFR for the visit was determined by averaging all valid PEFR measurements for the days between consecutive visits. |
| Mean Change From Baseline in Nocturnal Asthma Score on the Overnight Asthma Symptoms Diary in Nocturnal Asthmatic Patients Only | Baseline & over 16 weeks for the Beclo and MK + Beclo groups and over last 10 weeks for the Placebo and MK groups | Mean change from baseline in Nocturnal asthma score; the patient scored his/her symptoms \[from 0 (best) to 3 (worst)\] on a daily basis. Responses to the question, Did you wake up with asthma symptoms? (no, once, more than once, awake all night), were assigned numerical values (0, 1, 2, 3, respectively). The average score for the visit was determined by averaging the daily scores over all days between consecutive visits. |
Participant flow
Recruitment details
Patients were recruited at 22 sites in the United States (US) and 48 sites in 16 other countries in North America, Europe, Africa, Australia, and Southeast Asia. Publication incorrectly listed 18 participating countries. Results posting is correct with 17 countries. Prime therapy period: March 1995 to April 1996.
Pre-assignment details
Patients received inhaled beclomethasone (200 μg twice daily) starting at the Prestudy Visit and continuing through the single-blind run-in period. Patients who experienced worsening asthma requiring more than albuterol therapy (inhaled or nebulized) did not qualify for randomization.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Montelukast (MK) placebo tablet orally once daily at bedtime. Beclomethasone (beclo) inhaler was removed in a blinded, two-step procedure over 4 weeks (wks): beclomethasone inhaler 4 puffs (50 μg/puff) upon arising (Weeks 1 to 2)) and 4 puffs (50 μg/puff) at bedtime (Weeks 1 to 4); beclomethasone placebo inhaler 4 puffs upon arising (Weeks 3 to 16) and 4 puffs at bedtime (Weeks 5 to 16). Albuterol inhaler as needed. | 48 |
| Montelukast MK 10 mg tablet orally once daily at bedtime. Beclomethasone was removed in a blinded, two-step procedure over 4 weeks: beclomethasone inhaler 4 puffs (50 μg/puff) upon arising (Weeks 1 to 2) and 4 puffs (50 μg/puff) at bedtime (Weeks 1 to 4); beclomethasone placebo inhaler 4 puffs upon arising (Weeks 3 to 16) and 4 puffs at bedtime (Weeks 5 to 16). Albuterol inhaler as needed. | 201 |
| Beclomethasone MK placebo tablet orally once daily at bedtime and beclomethasone inhaler 4 puffs (50 μg/puff) upon arising and 4 puffs (50 μg/puff) at bedtime for 16 Weeks. Albuterol inhaler as needed. | 200 |
| Montelukast+ Beclomethasone MK 10 mg tablet orally once daily at bedtime and beclomethasone inhaler 4 puffs (50 μg/puff) upon arising and 4 puffs (50 μg/puff) at bedtime for 16 Weeks. Albuterol inhaler as needed. | 193 |
| Total | 642 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 27 | 11 | 6 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 | 1 |
| Overall Study | Protocol Violation | 0 | 5 | 5 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 10 | 4 | 8 |
Baseline characteristics
| Characteristic | Total | Placebo | Montelukast+ Beclomethasone | Beclomethasone | Montelukast |
|---|---|---|---|---|---|
| Age, Continuous | 39.00 years | 40.50 years | 40.00 years | 39.00 years | 38.00 years |
| Daytime symptom score | 2.18 Units on a Scale STANDARD_DEVIATION 0.82 | 2.36 Units on a Scale STANDARD_DEVIATION 0.68 | 2.17 Units on a Scale STANDARD_DEVIATION 0.84 | 2.17 Units on a Scale STANDARD_DEVIATION 0.82 | 2.14 Units on a Scale STANDARD_DEVIATION 0.83 |
| Forced expiratory volume in 1 second (FEV1) | 2.57 Liters STANDARD_DEVIATION 0.7 | 2.45 Liters STANDARD_DEVIATION 0.69 | 2.61 Liters STANDARD_DEVIATION 0.68 | 2.53 Liters STANDARD_DEVIATION 0.68 | 2.61 Liters STANDARD_DEVIATION 0.74 |
| Morning peak flow rate (PEFR) | 411.42 Liters/minute STANDARD_DEVIATION 88.92 | 406.80 Liters/minute STANDARD_DEVIATION 73.47 | 412.46 Liters/minute STANDARD_DEVIATION 91.15 | 402.91 Liters/minute STANDARD_DEVIATION 86.19 | 419.94 Liters/minute STANDARD_DEVIATION 92.47 |
| Nocturnal asthma score | 0.41 Units on a Scale STANDARD_DEVIATION 0.46 | 0.57 Units on a Scale STANDARD_DEVIATION 0.46 | 0.43 Units on a Scale STANDARD_DEVIATION 0.47 | 0.35 Units on a Scale STANDARD_DEVIATION 0.44 | 0.41 Units on a Scale STANDARD_DEVIATION 0.45 |
| Race/Ethnicity Black | 16 participants | 4 participants | 5 participants | 4 participants | 3 participants |
| Race/Ethnicity Caucasian | 590 participants | 40 participants | 177 participants | 184 participants | 189 participants |
| Race/Ethnicity Hispanic | 14 participants | 2 participants | 6 participants | 1 participants | 5 participants |
| Race/Ethnicity Other | 22 participants | 2 participants | 5 participants | 11 participants | 4 participants |
| Sex: Female, Male Female | 312 Participants | 29 Participants | 85 Participants | 96 Participants | 102 Participants |
| Sex: Female, Male Male | 330 Participants | 19 Participants | 108 Participants | 104 Participants | 99 Participants |
| Total daily Beta-agonist use | 3.53 Puffs STANDARD_DEVIATION 2.39 | 4.16 Puffs STANDARD_DEVIATION 3.02 | 3.41 Puffs STANDARD_DEVIATION 2.17 | 3.51 Puffs STANDARD_DEVIATION 2.47 | 3.52 Puffs STANDARD_DEVIATION 2.34 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 36 / 48 | 150 / 201 | 139 / 200 | 123 / 193 |
| serious Total, serious adverse events | 1 / 48 | 4 / 201 | 6 / 200 | 1 / 193 |
Outcome results
Primary
Mean Change From Baseline in Daytime Symptom Score on the Daytime Asthma Symptoms Diary in Patients With Chronic Asthma
The daily daytime symptom score was determined by averaging the daily scores (the patient scored his/her symptoms \[from 0 (best) to 6 (worst)\] on a daily basis.) for the four questions on the Daytime Asthma Symptoms Diary. The average daytime symptom score for the visit was determined by averaging the daily symptom scores over all days between two consecutive visits.
Time frame: Baseline & over 16 weeks for the Beclo and MK + Beclo groups and over last 10 weeks for the Placebo and MK groups
Population: Primary efficacy analyses were based on the intention-to-treat principle, i.e., inclusion of all patients with a baseline and at least one postbaseline measurement. No missing values for this analysis were imputed. Data collected during discontinuation visits and unscheduled visits were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Daytime Symptom Score on the Daytime Asthma Symptoms Diary in Patients With Chronic Asthma | 0.31 Units on a Scale |
| Montelukast | Mean Change From Baseline in Daytime Symptom Score on the Daytime Asthma Symptoms Diary in Patients With Chronic Asthma | 0.27 Units on a Scale |
| Beclomethasone | Mean Change From Baseline in Daytime Symptom Score on the Daytime Asthma Symptoms Diary in Patients With Chronic Asthma | -0.02 Units on a Scale |
| Montelukast+ Beclomethasone | Mean Change From Baseline in Daytime Symptom Score on the Daytime Asthma Symptoms Diary in Patients With Chronic Asthma | -0.13 Units on a Scale |
Primary
Mean Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) in Patients With Chronic Asthma
Mean percent change from baseline in FEV1 in patients with chronic asthma averaged over 16 weeks for the Beclo and MK+ Beclo groups and averaged over last 10 weeks for the Placebo and MK groups
Time frame: Baseline & over 16 weeks for the Beclomethasone (Beclo) and Montelukast (MK) + Beclo groups and over last 10 weeks for the Placebo and MK groups
Population: Primary efficacy analyses were based on the intention-to-treat principle, i.e., inclusion of all patients with a baseline and at least one postbaseline measurement. No missing values were imputed. Data collected during discontinuation and unscheduled visits were included the analysis. Differences between treatments are evaluated based on LS means
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) in Patients With Chronic Asthma | -11.96 Percentage of Change |
| Montelukast | Mean Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) in Patients With Chronic Asthma | -5.31 Percentage of Change |
| Beclomethasone | Mean Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) in Patients With Chronic Asthma | 0.72 Percentage of Change |
| Montelukast+ Beclomethasone | Mean Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) in Patients With Chronic Asthma | 5.08 Percentage of Change |
Secondary
Mean Change From Baseline in Morning Peak Flow Rate (PEFR) in Patients With Chronic Asthma
Morning PEFR was measured in triplicate immediately upon arising before taking any medication and the best value recorded on the overnight asthma symptoms diary. The mean morning PEFR for the visit was determined by averaging all valid PEFR measurements for the days between consecutive visits.
Time frame: Baseline & over 16 weeks for the Beclo and MK + Beclo groups and over last 10 weeks for the Placebo and MK groups
Population: Efficacy analyses were based on the intention-to-treat principle, i.e., inclusion of all patients with a baseline and at least one postbaseline measurement. No missing values for this analysis were imputed. Data collected during discontinuation visits and unscheduled visits were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Morning Peak Flow Rate (PEFR) in Patients With Chronic Asthma | -27.10 Liters/minute |
| Montelukast | Mean Change From Baseline in Morning Peak Flow Rate (PEFR) in Patients With Chronic Asthma | -15.37 Liters/minute |
| Beclomethasone | Mean Change From Baseline in Morning Peak Flow Rate (PEFR) in Patients With Chronic Asthma | 2.65 Liters/minute |
| Montelukast+ Beclomethasone | Mean Change From Baseline in Morning Peak Flow Rate (PEFR) in Patients With Chronic Asthma | 10.41 Liters/minute |
Secondary
Mean Change From Baseline in Nocturnal Asthma Score on the Overnight Asthma Symptoms Diary in Nocturnal Asthmatic Patients Only
Mean change from baseline in Nocturnal asthma score; the patient scored his/her symptoms \[from 0 (best) to 3 (worst)\] on a daily basis. Responses to the question, Did you wake up with asthma symptoms? (no, once, more than once, awake all night), were assigned numerical values (0, 1, 2, 3, respectively). The average score for the visit was determined by averaging the daily scores over all days between consecutive visits.
Time frame: Baseline & over 16 weeks for the Beclo and MK + Beclo groups and over last 10 weeks for the Placebo and MK groups
Population: Efficacy analyses were based on the intention-to-treat principle, i.e., inclusion of all patients with a baseline and at least one postbaseline measurement. No missing values for this analysis were imputed. Data collected during discontinuation visits and unscheduled visits were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Nocturnal Asthma Score on the Overnight Asthma Symptoms Diary in Nocturnal Asthmatic Patients Only | 0.17 Units on a Scale |
| Montelukast | Mean Change From Baseline in Nocturnal Asthma Score on the Overnight Asthma Symptoms Diary in Nocturnal Asthmatic Patients Only | 0.18 Units on a Scale |
| Beclomethasone | Mean Change From Baseline in Nocturnal Asthma Score on the Overnight Asthma Symptoms Diary in Nocturnal Asthmatic Patients Only | -0.06 Units on a Scale |
| Montelukast+ Beclomethasone | Mean Change From Baseline in Nocturnal Asthma Score on the Overnight Asthma Symptoms Diary in Nocturnal Asthmatic Patients Only | -0.20 Units on a Scale |
Secondary
Mean Percent Change From Baseline in Total Daily Beta-agonist Medication Use
Beta-agonist medication use from the daytime and overnight asthma symptoms diaries for each 24-hour period was added to determine the daily total number of puffs used. The average daily number of puffs for the visit was determined as the average daily number of puffs over all days between consecutive visits.
Time frame: Baseline & over 16 weeks for the Beclo and MK + Beclo groups and over last 10 weeks for the Placebo and MK groups
Population: Efficacy analyses were based on the intention-to-treat principle, i.e., inclusion of all patients with a baseline and at least one postbaseline measurement. No missing values for this analysis were imputed. Data collected during discontinuation visits and unscheduled visits were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Percent Change From Baseline in Total Daily Beta-agonist Medication Use | 59.20 Percent Change |
| Montelukast | Mean Percent Change From Baseline in Total Daily Beta-agonist Medication Use | 44.48 Percent Change |
| Beclomethasone | Mean Percent Change From Baseline in Total Daily Beta-agonist Medication Use | 6.04 Percent Change |
| Montelukast+ Beclomethasone | Mean Percent Change From Baseline in Total Daily Beta-agonist Medication Use | -5.51 Percent Change |