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

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00284856
• Collaborator: (none)
• Enrollment: 1,640
• Arms: 3
• Duration (Months): 47

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: montelukast sodium; Drug: Comparator: Placebo; Drug: Comparator: fluticasone; Drug: Comparator: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1640 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Parallel-Group 6-Month Study to Evaluate the Efficacy and Safety of Oral Montelukast Sodium, Fluticasone Propionate and Placebo in Patients With Chronic Asthma Who Smoke Cigarettes
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Arm 1: Montelukast	Drug: montelukast sodium; montelukast 10 mg tablet once daily, 6 month treatment period; Drug: Comparator: Placebo; fluticasone propionate 250 mcg Placebo (Pbo) twice daily, 6 month treatment period
Active Comparator: 2 Arm 2: Fluticasone	Drug: Comparator: fluticasone; fluticasone propionate 250 mcg twice daily, 6 month treatment period; Drug: Comparator: Placebo; montelukast 10 mg Pbo tablet once daily, 6 month treatment period
Placebo Comparator: 3 Arm 3: Placebo	Drug: Comparator: Placebo; fluticasone propionate 250 mcg Placebo (Pbo) twice daily, 6 month treatment period; Drug: Comparator: Placebo; montelukast 10 mg Pbo tablet once daily, 6 month treatment period

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00284856
• Other Study ID Numbers: 0476-332; 2005_108
• First Posted: Feb 1, 2006
• Last Update Posted: Feb 7, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Asthma; Fluticasone; Montelukast

Study Results

Participant Flow

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

Arm/Group Title	Montelukast	Fluticasone	Placebo
Arm/Group Description	Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months	Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months
Period Title: Overall Study
STARTED	347	336	336
COMPLETED	296	286	276
NOT COMPLETED	51	50	60

Baseline Characteristics

Arm/Group Title	Montelukast	Fluticasone	Placebo	Total
Arm/Group Description	Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months	Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Total of all reporting groups
Overall Participants	347	336	336	1019
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.7 (10.4)	38.4 (10.7)	37.9 (9.9)	38.0 (10.3)
Sex: Female, Male (Count of Participants)
Female	163 47%	147 43.8%	166 49.4%	476 46.7%
Male	184 53%	189 56.3%	170 50.6%	543 53.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Asthma-control Days Over the 6-month Treatment Period
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Montelukast	Fluticasone	Placebo
Arm/Group Description	Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months	Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months
Measure Participants	334	329	323
Mean (Standard Deviation) [Percentage of days]	50.70 (38.19)	53.30 (39.06)	43.84 (38.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Montelukast, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	5.92
	Confidence Interval	() 95%; 0.28 to 11.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated Value is difference in least squares mean (montelukast - placebo)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fluticasone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	10.14
	Confidence Interval	() 95%; 4.50 to 15.78
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value is difference in least squares mean (fluticasone - placebo)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Montelukast, Fluticasone
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-4.22
	Confidence Interval	() 95%; -9.83 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value is difference in least squares mean (montelukast - fluticasone)

2. Secondary Outcome

Title	Change From Baseline in Mean Daytime Symptom Score Over a 6-month Treatment Period
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Montelukast	Fluticasone	Placebo
Arm/Group Description	Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months	Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months
Measure Participants	335	329	322
Baseline	1.82 (1.03)	1.78 (0.97)	1.90 (0.94)
Average Change from Baseline During Period II	-0.41 (0.70)	-0.44 (0.68)	-0.27 (0.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Montelukast, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.15
	Confidence Interval	() 95%; -0.25 to -0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value is difference in least squares mean (montelukast - placebo)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fluticasone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.20
	Confidence Interval	() 95%; -0.30 to -0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value is difference in least squares mean (fluticasone - placebo)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Montelukast, Fluticasone
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.05
	Confidence Interval	() 95%; -0.05 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value is difference in least squares mean (montelukast - fluticasone)

3. Secondary Outcome

Title	Change From Baseline in Average Morning (AM) PEFR (Peak Expiratory Flow Rate) Over a 6-month Treatment Period
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Montelukast	Fluticasone	Placebo
Arm/Group Description	Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months	Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months	Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months
Measure Participants	334	329	324
Baseline	363.75 (112.40)	354.28 (101.64)	347.98 (99.21)
Average Change from Baseline During Period II	12.84 (40.22)	19.31 (44.85)	8.27 (40.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Montelukast, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	5.09
	Confidence Interval	() 95%; -1.27 to 11.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value is difference in least squares mean (montelukast - placebo)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fluticasone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	11.21
	Confidence Interval	() 95%; 4.85 to 17.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value is difference in least squares mean (fluticasone - placebo)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Montelukast, Fluticasone
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-6.13
	Confidence Interval	() 95%; -12.46 to 0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value is difference in least squares mean (montelukast - fluticasone)

Adverse Events

Adverse Event Reporting Description	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.
Arm/Group Title	Montelukast		Fluticasone		Placebo
Arm/Group Description	Montelukast 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months		Fluticasone propionate 250 mcg twice daily and Montelukast matching placebo 10 mg tablet once daily at bedtime for 6 months		Montelukast matching placebo 10 mg tablet once daily at bedtime and Fluticasone propionate matching placebo 250 mcg twice daily for 6 months
All Cause Mortality
	Montelukast		Fluticasone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Montelukast		Fluticasone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/347 (2.6%)		10/336 (3%)		11/335 (3.3%)
Cardiac disorders
Cardiac arrest	0/347 (0%)	0	1/336 (0.3%)	1	0/335 (0%)	0
Congenital, familial and genetic disorders
Dermoid cyst	1/347 (0.3%)	1	0/336 (0%)	0	0/335 (0%)	0
Gastrointestinal disorders
Haemorrhoids	0/347 (0%)	0	1/336 (0.3%)	1	0/335 (0%)	0
Hiatus hernia	0/347 (0%)	0	0/336 (0%)	0	1/335 (0.3%)	1
Hepatobiliary disorders
Autoimmune hepatitis	0/347 (0%)	0	1/336 (0.3%)	1	0/335 (0%)	0
Cholecystitis	1/347 (0.3%)	1	0/336 (0%)	0	0/335 (0%)	0
Infections and infestations
Appendicitis	0/347 (0%)	0	0/336 (0%)	0	1/335 (0.3%)	1
Endometritis	1/347 (0.3%)	1	0/336 (0%)	0	0/335 (0%)	0
Respiratory tract infection	0/347 (0%)	0	0/336 (0%)	0	1/335 (0.3%)	1
Salpingo-oophoritis	1/347 (0.3%)	1	0/336 (0%)	0	0/335 (0%)	0
Upper respiratory tract infection	1/347 (0.3%)	1	0/336 (0%)	0	0/335 (0%)	0
Urinary tract infection	1/347 (0.3%)	1	0/336 (0%)	0	0/335 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	0/347 (0%)	0	2/336 (0.6%)	2	6/335 (1.8%)	7
Brain herniation	0/347 (0%)	0	1/336 (0.3%)	1	0/335 (0%)	0
Intentional overdose	0/347 (0%)	0	0/336 (0%)	0	1/335 (0.3%)	1
Post procedural haemorrhage	0/347 (0%)	0	1/336 (0.3%)	1	0/335 (0%)	0
Rib fracture	0/347 (0%)	0	0/336 (0%)	0	1/335 (0.3%)	1
Musculoskeletal and connective tissue disorders
Bursitis	1/347 (0.3%)	1	0/336 (0%)	0	0/335 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	0/347 (0%)	0	1/336 (0.3%)	1	0/335 (0%)	0
Nervous system disorders
Cerebral infarction	1/347 (0.3%)	1	0/336 (0%)	0	0/335 (0%)	0
Cerebrovascular accident	1/347 (0.3%)	1	0/336 (0%)	0	0/335 (0%)	0
Facial palsy	1/347 (0.3%)	1	0/336 (0%)	0	0/335 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	1/347 (0.3%)	1	2/336 (0.6%)	5	2/335 (0.6%)	3
Asthmatic crisis	0/347 (0%)	0	1/336 (0.3%)	1	0/335 (0%)	0
Surgical and medical procedures
Abortion induced	0/347 (0%)	0	1/336 (0.3%)	1	0/335 (0%)	0
Other (Not Including Serious) Adverse Events
	Montelukast		Fluticasone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/347 (18.7%)		57/336 (17%)		72/335 (21.5%)
Infections and infestations
Nasopharyngitis	23/347 (6.6%)	30	27/336 (8%)	34	22/335 (6.6%)	26
Respiratory, thoracic and mediastinal disorders
Asthma	45/347 (13%)	71	34/336 (10.1%)	50	57/335 (17%)	95

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.