Trial Outcomes & Findings for Study of Inhaled Corticosteroid Plus Montelukast Compared With Inhaled Corticosteroid Therapy Alone in Patients With Chronic Asthma (0476-386) (NCT NCT00666679)
NCT ID: NCT00666679
Last Updated: 2024-05-10
Results Overview
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.
COMPLETED
PHASE2
134 participants
Baseline and 2 weeks
2024-05-10
Participant Flow
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.
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.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
First Intervention
STARTED
|
66
|
68
|
|
First Intervention
COMPLETED
|
62
|
67
|
|
First Intervention
NOT COMPLETED
|
4
|
1
|
|
Washout Period of 1 Week
STARTED
|
62
|
67
|
|
Washout Period of 1 Week
COMPLETED
|
62
|
65
|
|
Washout Period of 1 Week
NOT COMPLETED
|
0
|
2
|
|
Second Intervention
STARTED
|
62
|
65
|
|
Second Intervention
COMPLETED
|
61
|
64
|
|
Second Intervention
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
First Intervention
Lost to Follow-up
|
1
|
0
|
|
First Intervention
Protocol Violation
|
1
|
0
|
|
First Intervention
Withdrawal by Subject
|
1
|
0
|
|
First Intervention
Randomized did not start treatment
|
1
|
1
|
|
Washout Period of 1 Week
Lost to Follow-up
|
0
|
1
|
|
Washout Period of 1 Week
Protocol Violation
|
0
|
1
|
|
Second Intervention
Adverse Event
|
1
|
0
|
|
Second Intervention
Death
|
0
|
1
|
Baseline Characteristics
Study of Inhaled Corticosteroid Plus Montelukast Compared With Inhaled Corticosteroid Therapy Alone in Patients With Chronic Asthma (0476-386)
Baseline characteristics by cohort
| Measure |
Montelukast + Mometasone Then Placebo + Mometasone
n=66 Participants
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.
|
Placebo + Mometasone Then Montelukast + Mometasone
n=68 Participants
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.
|
Total
n=134 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
39.2 years
STANDARD_DEVIATION 15.5 • n=93 Participants
|
42.6 years
STANDARD_DEVIATION 14.8 • n=4 Participants
|
40.9 years
STANDARD_DEVIATION 15.2 • n=27 Participants
|
|
Sex: Female, Male
Female
|
37 Participants
n=93 Participants
|
32 Participants
n=4 Participants
|
69 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=93 Participants
|
36 Participants
n=4 Participants
|
65 Participants
n=27 Participants
|
|
Daytime Asthma Symptom Score (0 [best] to 6 [worst] Point Scale)
|
2.04 Units on a Scale
STANDARD_DEVIATION 0.90 • n=93 Participants
|
2.18 Units on a Scale
STANDARD_DEVIATION 0.81 • n=4 Participants
|
2.11 Units on a Scale
STANDARD_DEVIATION 0.85 • n=27 Participants
|
|
FEV1 (Forced Expiratory Volume in One Second)
|
2.14 L (Liter)
STANDARD_DEVIATION 0.67 • n=93 Participants
|
2.18 L (Liter)
STANDARD_DEVIATION 0.55 • n=4 Participants
|
2.16 L (Liter)
STANDARD_DEVIATION 0.61 • n=27 Participants
|
|
Nighttime Asthma Symptom Score (0 [best] to 3 [worst] Point Scale)
|
0.51 Units on a Scale
STANDARD_DEVIATION 0.53 • n=93 Participants
|
0.46 Units on a Scale
STANDARD_DEVIATION 0.48 • n=4 Participants
|
0.49 Units on a Scale
STANDARD_DEVIATION 0.50 • n=27 Participants
|
|
Total Daily Beta-Agonist Use
|
3.52 Puffs
STANDARD_DEVIATION 2.49 • n=93 Participants
|
3.55 Puffs
STANDARD_DEVIATION 2.19 • n=4 Participants
|
3.53 Puffs
STANDARD_DEVIATION 2.34 • n=27 Participants
|
|
Total Peripheral Blood Eosinophils
|
0.46 10^3/microliters
STANDARD_DEVIATION 0.39 • n=93 Participants
|
0.38 10^3/microliters
STANDARD_DEVIATION 0.31 • n=4 Participants
|
0.42 10^3/microliters
STANDARD_DEVIATION 0.35 • n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline and 2 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Montelukast + Mometasone
n=127 Participants
Inhaled montelukast 1mg (milligram) and open label mometasone 220 mcg (micrograms) once daily.
|
Placebo + Mometasone
n=127 Participants
Inhaled placebo for montelukast and open label mometasone 220 mcg once daily.
|
|---|---|---|
|
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)
Interval 0.15 to 0.3
|
0.17 L (Liter)
Interval 0.11 to 0.23
|
SECONDARY outcome
Timeframe: Baseline and 2 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Montelukast + Mometasone
n=128 Participants
Inhaled montelukast 1mg (milligram) and open label mometasone 220 mcg (micrograms) once daily.
|
Placebo + Mometasone
n=129 Participants
Inhaled placebo for montelukast and open label mometasone 220 mcg once daily.
|
|---|---|---|
|
Change From Baseline in Daytime Asthma Symptom Score
|
-0.39 Units on a Scale
Interval -0.49 to -0.29
|
-0.24 Units on a Scale
Interval -0.35 to -0.12
|
SECONDARY outcome
Timeframe: Baseline and 2 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Montelukast + Mometasone
n=89 Participants
Inhaled montelukast 1mg (milligram) and open label mometasone 220 mcg (micrograms) once daily.
|
Placebo + Mometasone
n=90 Participants
Inhaled placebo for montelukast and open label mometasone 220 mcg once daily.
|
|---|---|---|
|
Change From Baseline in Nighttime Asthma Symptom Score
|
-0.28 Units on a Scale
Interval -0.35 to -0.2
|
-0.18 Units on a Scale
Interval -0.28 to -0.09
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and 2 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Montelukast + Mometasone
n=128 Participants
Inhaled montelukast 1mg (milligram) and open label mometasone 220 mcg (micrograms) once daily.
|
Placebo + Mometasone
n=128 Participants
Inhaled placebo for montelukast and open label mometasone 220 mcg once daily.
|
|---|---|---|
|
Change From Baseline in Total Daily β-agonist Use
|
-0.87 Puffs
Interval -1.21 to -0.53
|
-0.27 Puffs
Interval -0.86 to 0.32
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 2 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Montelukast + Mometasone
n=129 Participants
Inhaled montelukast 1mg (milligram) and open label mometasone 220 mcg (micrograms) once daily.
|
Placebo + Mometasone
n=129 Participants
Inhaled placebo for montelukast and open label mometasone 220 mcg once daily.
|
|---|---|---|
|
Percentage of Days With Asthma Control
|
35.13 Percentage of Days
Interval 28.52 to 41.74
|
29.04 Percentage of Days
Interval 22.98 to 35.11
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 2 WeeksPopulation: 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.
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.
Outcome measures
| Measure |
Montelukast + Mometasone
n=127 Participants
Inhaled montelukast 1mg (milligram) and open label mometasone 220 mcg (micrograms) once daily.
|
Placebo + Mometasone
n=127 Participants
Inhaled placebo for montelukast and open label mometasone 220 mcg once daily.
|
|---|---|---|
|
Percentage of Days With Asthma Exacerbations
|
9.71 Percentage of Days
Interval 5.51 to 13.9
|
15.14 Percentage of Days
Interval 10.94 to 19.33
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and 2 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Montelukast + Mometasone
n=119 Participants
Inhaled montelukast 1mg (milligram) and open label mometasone 220 mcg (micrograms) once daily.
|
Placebo + Mometasone
n=119 Participants
Inhaled placebo for montelukast and open label mometasone 220 mcg once daily.
|
|---|---|---|
|
Change From Baseline in Total Peripheral Blood Eosinophils
|
-0.05 10^3/microliter
Interval -0.09 to -0.01
|
0.02 10^3/microliter
Interval -0.03 to 0.06
|
POST_HOC outcome
Timeframe: Baseline and 2 WeeksPopulation: 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.
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.
Outcome measures
| Measure |
Montelukast + Mometasone
n=99 Participants
Inhaled montelukast 1mg (milligram) and open label mometasone 220 mcg (micrograms) once daily.
|
Placebo + Mometasone
n=99 Participants
Inhaled placebo for montelukast and open label mometasone 220 mcg once daily.
|
|---|---|---|
|
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)
Interval 0.19 to 0.35
|
0.19 L (Liter)
Interval 0.12 to 0.26
|
Adverse Events
Montelukast + Mometasone
Placebo + Mometasone
Serious adverse events
| Measure |
Montelukast + Mometasone
n=130 participants at risk
Inhaled montelukast 1 mg (milligram) and open label mometasone 220 mcg (micrograms) once daily.
|
Placebo + Mometasone
n=129 participants at risk
Inhaled placebo for montelukast and open label mometasone 220 mcg once daily.
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.77%
1/130
|
0.00%
0/129
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.77%
1/130
|
0.00%
0/129
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/130
|
0.78%
1/129
|
Other adverse events
| Measure |
Montelukast + Mometasone
n=130 participants at risk
Inhaled montelukast 1 mg (milligram) and open label mometasone 220 mcg (micrograms) once daily.
|
Placebo + Mometasone
n=129 participants at risk
Inhaled placebo for montelukast and open label mometasone 220 mcg once daily.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/130
|
0.78%
1/129
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
0.77%
1/130
|
1.6%
2/129
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/130
|
0.78%
1/129
|
|
Gastrointestinal disorders
Stomach discomfort
|
0.77%
1/130
|
0.00%
0/129
|
|
General disorders
Asthenia
|
0.00%
0/130
|
0.78%
1/129
|
|
General disorders
Irritability
|
0.00%
0/130
|
0.78%
1/129
|
|
General disorders
Pyrexia
|
0.77%
1/130
|
0.00%
0/129
|
|
Infections and infestations
Acarodermatitis
|
0.00%
0/130
|
0.78%
1/129
|
|
Infections and infestations
Gastroenteritis viral
|
0.77%
1/130
|
0.00%
0/129
|
|
Infections and infestations
Herpes simplex
|
0.77%
1/130
|
0.00%
0/129
|
|
Infections and infestations
Influenza
|
0.77%
1/130
|
0.00%
0/129
|
|
Infections and infestations
Nasopharyngitis
|
3.8%
5/130
|
2.3%
3/129
|
|
Infections and infestations
Pharyngitis
|
1.5%
2/130
|
0.00%
0/129
|
|
Infections and infestations
Pulpitis dental
|
0.00%
0/130
|
0.78%
1/129
|
|
Infections and infestations
Sinusitis
|
0.77%
1/130
|
0.78%
1/129
|
|
Infections and infestations
Upper respiratory tract infection
|
2.3%
3/130
|
0.78%
1/129
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/130
|
1.6%
2/129
|
|
Infections and infestations
Viral infection
|
0.77%
1/130
|
1.6%
2/129
|
|
Infections and infestations
Viral pharyngitis
|
0.00%
0/130
|
0.78%
1/129
|
|
Infections and infestations
Viral rhinitis
|
0.00%
0/130
|
0.78%
1/129
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/130
|
0.78%
1/129
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/130
|
0.78%
1/129
|
|
Investigations
Blood cholesterol increased
|
0.00%
0/130
|
0.78%
1/129
|
|
Investigations
Eosinophil count increased
|
1.5%
2/130
|
0.78%
1/129
|
|
Investigations
White blood cells urine positive
|
0.00%
0/130
|
0.78%
1/129
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.77%
1/130
|
0.00%
0/129
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/130
|
0.78%
1/129
|
|
Nervous system disorders
Headache
|
0.77%
1/130
|
0.78%
1/129
|
|
Nervous system disorders
Migraine
|
0.77%
1/130
|
1.6%
2/129
|
|
Respiratory, thoracic and mediastinal disorders
Allergic pharyngitis
|
0.77%
1/130
|
0.78%
1/129
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
1.5%
2/130
|
3.9%
5/129
|
|
Respiratory, thoracic and mediastinal disorders
Asthmatic crisis
|
0.77%
1/130
|
0.00%
0/129
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.77%
1/130
|
0.00%
0/129
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.77%
1/130
|
0.78%
1/129
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.77%
1/130
|
0.00%
0/129
|
|
Skin and subcutaneous tissue disorders
Dermatitis atopic
|
0.00%
0/130
|
0.78%
1/129
|
|
Skin and subcutaneous tissue disorders
Pityriasis rosea
|
0.77%
1/130
|
0.00%
0/129
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER