Trial Outcomes & Findings for Montelukast Asthmatic Smoker Study (0476-332)(COMPLETED) (NCT NCT00284856)

Last Updated: 2024-05-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1640 participants

Primary outcome timeframe

6 months

Results posted on

2024-05-10

Participant Flow

Of the 1640 participants enrolled in the study, 621 participants were excluded during screening and not randomized. The remaining 1019 participants were randomized.

Participant milestones

Participant milestones
Measure	Montelukast Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Fluticasone Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months	Placebo Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months
Overall Study STARTED	347	336	336
Overall Study COMPLETED	296	286	276
Overall Study NOT COMPLETED	51	50	60

Reasons for withdrawal

Reasons for withdrawal
Measure	Montelukast Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Fluticasone Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months	Placebo Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months
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 Protocol Violation	5	4	5
Overall Study Withdrawal by Subject	12	16	18
Overall Study Other	4	5	4

Baseline Characteristics

Montelukast Asthmatic Smoker Study (0476-332)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Montelukast n=347 Participants Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Fluticasone n=336 Participants Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months	Placebo n=336 Participants Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Total n=1019 Participants Total of all reporting groups
Age, Continuous	37.7 years STANDARD_DEVIATION 10.4 • n=5 Participants	38.4 years STANDARD_DEVIATION 10.7 • n=7 Participants	37.9 years STANDARD_DEVIATION 9.9 • n=5 Participants	38.0 years STANDARD_DEVIATION 10.3 • n=4 Participants
Sex: Female, Male Female	163 Participants n=5 Participants	147 Participants n=7 Participants	166 Participants n=5 Participants	476 Participants n=4 Participants
Sex: Female, Male Male	184 Participants n=5 Participants	189 Participants n=7 Participants	170 Participants n=5 Participants	543 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Montelukast n=334 Participants Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Fluticasone n=329 Participants Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months	Placebo n=323 Participants Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months
Percentage of Asthma-control Days Over the 6-month Treatment Period	50.70 Percentage of days Standard Deviation 38.19 • Interval 40.62 to 49.33	53.30 Percentage of days Standard Deviation 39.06 • Interval 44.86 to 53.53	43.84 Percentage of days Standard Deviation 38.08 • Interval 34.65 to 43.45

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Montelukast n=335 Participants Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Fluticasone n=329 Participants Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months	Placebo n=322 Participants Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months
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 • Interval -0.53 to -0.37	1.78 Score on a scale Standard Deviation 0.97 • Interval -0.58 to -0.42	1.90 Score on a scale Standard Deviation 0.94 • Interval -0.38 to -0.23
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 0.70	-0.44 Score on a scale Standard Deviation 0.68	-0.27 Score on a scale Standard Deviation 0.72

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Montelukast n=334 Participants Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Fluticasone n=329 Participants Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months	Placebo n=324 Participants Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months
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 112.40	354.28 Liters/minute Standard Deviation 101.64	347.98 Liters/minute Standard Deviation 99.21
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	19.31 Liters/minute Standard Deviation 44.85	8.27 Liters/minute Standard Deviation 40.70

Adverse Events

Montelukast

Serious events: 9 serious events

Other events: 65 other events

Deaths: 0 deaths

Fluticasone

Serious events: 10 serious events

Other events: 57 other events

Deaths: 0 deaths

Placebo

Serious events: 11 serious events

Other events: 72 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Montelukast n=347 participants at risk Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Fluticasone n=336 participants at risk Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months	Placebo n=335 participants at risk Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months
Infections and infestations Nasopharyngitis	6.6% 23/347 • Number of events 30 The population for safety analyses was the All Patients as Treated (APaT) set. The set included all randomized participants who took at least one dose of the double-blind study medication. One participant in the placebo group was randomized but did not take treatment. Therefore, participant was not included in the safety analyses.	8.0% 27/336 • Number of events 34 The population for safety analyses was the All Patients as Treated (APaT) set. The set included all randomized participants who took at least one dose of the double-blind study medication. One participant in the placebo group was randomized but did not take treatment. Therefore, participant was not included in the safety analyses.	6.6% 22/335 • Number of events 26 The population for safety analyses was the All Patients as Treated (APaT) set. The set included all randomized participants who took at least one dose of the double-blind study medication. One participant in the placebo group was randomized but did not take treatment. Therefore, participant was not included in the safety analyses.
Respiratory, thoracic and mediastinal disorders Asthma	13.0% 45/347 • Number of events 71 The population for safety analyses was the All Patients as Treated (APaT) set. The set included all randomized participants who took at least one dose of the double-blind study medication. One participant in the placebo group was randomized but did not take treatment. Therefore, participant was not included in the safety analyses.	10.1% 34/336 • Number of events 50 The population for safety analyses was the All Patients as Treated (APaT) set. The set included all randomized participants who took at least one dose of the double-blind study medication. One participant in the placebo group was randomized but did not take treatment. Therefore, participant was not included in the safety analyses.	17.0% 57/335 • Number of events 95 The population for safety analyses was the All Patients as Treated (APaT) set. The set included all randomized participants who took at least one dose of the double-blind study medication. One participant in the placebo group was randomized but did not take treatment. Therefore, participant was not included in the safety analyses.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication guidelines.
Publication restrictions are in place

Restriction type: OTHER