Asthma
Conditions
Brief summary
This is a multicenter study to evaluate the efficacy and safety of MK0476 versus placebo in participants with chronic asthma who actively smoke cigarettes.
Interventions
DRUGmontelukast sodium
montelukast 10 mg tablet once daily, 6 month treatment period
DRUGComparator: Placebo
fluticasone propionate 250 mcg Placebo (Pbo) twice daily, 6 month treatment period
fluticasone propionate 250 mcg twice daily, 6 month treatment period
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Participants with chronic asthma who actively smoke at least 0.5 to no more than 2 packs of cigarettes a day
Exclusion criteria
* Participant cannot have a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) or emphysema.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Asthma-control Days Over the 6-month Treatment Period | 6 months | An asthma-control day, computed from daily diaries, was any day with no unscheduled visit for asthma care, no use of \> than 2 puffs of β-agonist, no use of other asthma rescue medication, and no nocturnal awakening. The percentage of asthma-control days was the number of days with asthma-control divided by the total number of days with non-missing values for this endpoint. The patient diary had questions concerning daytime and nighttime symptoms, morning (AM) and evening (PM) peak expiratory flow rate (PEFR), β-agonist use, asthma attacks and smoking activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Daytime Symptom Score Over a 6-month Treatment Period | Baseline and 6 months | 4 daytime symptoms were evaluated daily on a 7-point scale from 0 (best)- 6 (worst). The on-treatment daytime symptom score was computed by averaging over Period II the mean of the 4 daily symptom scores recorded daily in the diary while the baseline daytime symptom score was obtained by averaging the mean of the 4 daily symptom scores across the daily diary entries of the Baseline period (Period I). The change from baseline in mean daytime symptom score is computed as the difference between the mean on-treatment daytime symptom score & the mean baseline daytime symptom score. |
| Change From Baseline in Average Morning (AM) PEFR (Peak Expiratory Flow Rate) Over a 6-month Treatment Period | Baseline and 6 months | PEFR measurements were performed daily, in the morning before using any medication. The on-treatment AM PEFR was computed by averaging over Period II (treatment period) the AM PEFR recorded daily in the diary, while the baseline AM PEFR was obtained by averaging the AM PEFR across the daily diary entries of the Baseline Period or Period I (placebo run-in period). The change from baseline in average AM PEFR is computed as the difference between mean on-treatment AM PEFR and mean baseline AM PEFR. |
Participant flow
Pre-assignment details
Of the 1640 participants enrolled in the study, 621 participants were excluded during screening and not randomized. The remaining 1019 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Montelukast Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months | 347 |
| Fluticasone Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months | 336 |
| Placebo Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months | 336 |
| Total | 1,019 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 | 3 |
| Overall Study | Lack of Efficacy | 2 | 1 | 8 |
| Overall Study | Lost to Follow-up | 25 | 21 | 22 |
| Overall Study | Other | 4 | 5 | 4 |
| Overall Study | Protocol Violation | 5 | 4 | 5 |
| Overall Study | Withdrawal by Subject | 12 | 16 | 18 |
Baseline characteristics
| Characteristic | Montelukast | Fluticasone | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 37.7 years STANDARD_DEVIATION 10.4 | 38.4 years STANDARD_DEVIATION 10.7 | 37.9 years STANDARD_DEVIATION 9.9 | 38.0 years STANDARD_DEVIATION 10.3 |
| Sex: Female, Male Female | 163 Participants | 147 Participants | 166 Participants | 476 Participants |
| Sex: Female, Male Male | 184 Participants | 189 Participants | 170 Participants | 543 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 65 / 347 | 57 / 336 | 72 / 335 |
| serious Total, serious adverse events | 9 / 347 | 10 / 336 | 11 / 335 |
Outcome results
Primary
Percentage of Asthma-control Days Over the 6-month Treatment Period
An asthma-control day, computed from daily diaries, was any day with no unscheduled visit for asthma care, no use of \> than 2 puffs of β-agonist, no use of other asthma rescue medication, and no nocturnal awakening. The percentage of asthma-control days was the number of days with asthma-control divided by the total number of days with non-missing values for this endpoint. The patient diary had questions concerning daytime and nighttime symptoms, morning (AM) and evening (PM) peak expiratory flow rate (PEFR), β-agonist use, asthma attacks and smoking activity.
Time frame: 6 months
Population: Efficacy analysis was based on the full analysis set (FAS) population which included all participants who had at least 7 days of on-treatment data for the specific endpoint. Thirty three patients were excluded from the FAS (13 on montelukast, 7 on fluticasone and 13 on placebo). One participant in the placebo group did not take study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Montelukast | Percentage of Asthma-control Days Over the 6-month Treatment Period | 50.70 Percentage of days | Standard Deviation 38.19 |
| Fluticasone | Percentage of Asthma-control Days Over the 6-month Treatment Period | 53.30 Percentage of days | Standard Deviation 39.06 |
| Placebo | Percentage of Asthma-control Days Over the 6-month Treatment Period | 43.84 Percentage of days | Standard Deviation 38.08 |
95% CI: [0.28, 11.56]
95% CI: [4.5, 15.78]
95% CI: [-9.83, 1.38]
Secondary
Change From Baseline in Average Morning (AM) PEFR (Peak Expiratory Flow Rate) Over a 6-month Treatment Period
PEFR measurements were performed daily, in the morning before using any medication. The on-treatment AM PEFR was computed by averaging over Period II (treatment period) the AM PEFR recorded daily in the diary, while the baseline AM PEFR was obtained by averaging the AM PEFR across the daily diary entries of the Baseline Period or Period I (placebo run-in period). The change from baseline in average AM PEFR is computed as the difference between mean on-treatment AM PEFR and mean baseline AM PEFR.
Time frame: Baseline and 6 months
Population: Efficacy analysis was based on the full analysis set (FAS) population which included all participants who received at least one dose of the randomized double-blind study medication and who had at least 7 days of on-treatment data for the specific endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Montelukast | Change From Baseline in Average Morning (AM) PEFR (Peak Expiratory Flow Rate) Over a 6-month Treatment Period | Baseline | 363.75 Liters/minute | Standard Deviation 112.4 |
| Montelukast | Change From Baseline in Average Morning (AM) PEFR (Peak Expiratory Flow Rate) Over a 6-month Treatment Period | Average Change from Baseline During Period II | 12.84 Liters/minute | Standard Deviation 40.22 |
| Fluticasone | Change From Baseline in Average Morning (AM) PEFR (Peak Expiratory Flow Rate) Over a 6-month Treatment Period | Baseline | 354.28 Liters/minute | Standard Deviation 101.64 |
| Fluticasone | Change From Baseline in Average Morning (AM) PEFR (Peak Expiratory Flow Rate) Over a 6-month Treatment Period | Average Change from Baseline During Period II | 19.31 Liters/minute | Standard Deviation 44.85 |
| Placebo | Change From Baseline in Average Morning (AM) PEFR (Peak Expiratory Flow Rate) Over a 6-month Treatment Period | Baseline | 347.98 Liters/minute | Standard Deviation 99.21 |
| Placebo | Change From Baseline in Average Morning (AM) PEFR (Peak Expiratory Flow Rate) Over a 6-month Treatment Period | Average Change from Baseline During Period II | 8.27 Liters/minute | Standard Deviation 40.7 |
95% CI: [-1.27, 11.45]
95% CI: [4.85, 17.58]
95% CI: [-12.46, 0.2]
Secondary
Change From Baseline in Mean Daytime Symptom Score Over a 6-month Treatment Period
4 daytime symptoms were evaluated daily on a 7-point scale from 0 (best)- 6 (worst). The on-treatment daytime symptom score was computed by averaging over Period II the mean of the 4 daily symptom scores recorded daily in the diary while the baseline daytime symptom score was obtained by averaging the mean of the 4 daily symptom scores across the daily diary entries of the Baseline period (Period I). The change from baseline in mean daytime symptom score is computed as the difference between the mean on-treatment daytime symptom score & the mean baseline daytime symptom score.
Time frame: Baseline and 6 months
Population: Efficacy analysis was based on the full analysis set (FAS) population which included all participants who received at least one dose of the randomized double-blind study medication and who had at least 7 days of on-treatment data for the specific endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Montelukast | Change From Baseline in Mean Daytime Symptom Score Over a 6-month Treatment Period | Baseline | 1.82 Score on a scale | Standard Deviation 1.03 |
| Montelukast | Change From Baseline in Mean Daytime Symptom Score Over a 6-month Treatment Period | Average Change from Baseline During Period II | -0.41 Score on a scale | Standard Deviation 0.7 |
| Fluticasone | Change From Baseline in Mean Daytime Symptom Score Over a 6-month Treatment Period | Baseline | 1.78 Score on a scale | Standard Deviation 0.97 |
| Fluticasone | Change From Baseline in Mean Daytime Symptom Score Over a 6-month Treatment Period | Average Change from Baseline During Period II | -0.44 Score on a scale | Standard Deviation 0.68 |
| Placebo | Change From Baseline in Mean Daytime Symptom Score Over a 6-month Treatment Period | Baseline | 1.90 Score on a scale | Standard Deviation 0.94 |
| Placebo | Change From Baseline in Mean Daytime Symptom Score Over a 6-month Treatment Period | Average Change from Baseline During Period II | -0.27 Score on a scale | Standard Deviation 0.72 |
95% CI: [-0.25, -0.05]
95% CI: [-0.3, -0.1]
95% CI: [-0.05, 0.15]