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Clinical Trial Results:
A Multicenter, Double-Blind, Randomized, Cross-Over Design Study to Evaluate the Effect of Montelukast vs. Salmeterol on the Inhibition of Exercise-Induced Bronchoconstriction in Asthmatic Patients Aged 6-14 Years.

Summary
EudraCT number	2004-004709-53
Trial protocol	EE ES IT Outside EU/EEA
Global end of trial date	14 Nov 2008

Results information
Results version number	v1(current)
This version publication date	27 Apr 2016
First version publication date	15 Jul 2015
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

MK-0476-911

ISRCTN number

US NCT number

NCT00127166

WHO universal trial number (UTN)

Other trial identifiers

Merck Protocol Number: MK-0476-911

Sponsor organisation name

Merck Sharp & Dohme Corp.

Sponsor organisation address

2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

14 Nov 2008

Is this the analysis of the primary completion data?

Yes

Primary completion date

14 Nov 2008

Global end of trial reached?

Yes

Global end of trial date

14 Nov 2008

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study is to determine the effect of four weeks of treatment with two investigational drugs (oral versus inhaled administration) plus an inhaled medication in the treatment of airway constriction brought on by exercise in participants with asthma.

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research. The following additional measure defined for this individual study was in place for the protection of trial subjects: salbutamol was to be used throughout all periods on an “as needed” basis for rescue.

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Dec 2005

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 2

Country: Number of subjects enrolled

Estonia: 17

Country: Number of subjects enrolled

Italy: 13

Country: Number of subjects enrolled

Brazil: 41

Country: Number of subjects enrolled

Colombia: 25

Country: Number of subjects enrolled

Croatia: 3

Country: Number of subjects enrolled

Greece: 11

Country: Number of subjects enrolled

Mexico: 8

Country: Number of subjects enrolled

Peru: 20

Country: Number of subjects enrolled

Poland: 14

Worldwide total number of subjects

154

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

112

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

For randomization, participants fulfilled the following criteria: 1. Forced Expiratory Volume in one second (FEV1) ≥70% predicted while withholding beta (β)-agonist for at least 6 hours 2. Exercise-induced bronchoconstriction (EIB) showing FEV1 ≥15% reduction from baseline while on inhaled corticosteroids demonstrated twice during the run-in period

Period 1 title

Period I

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Montelukast / Salmeterol

Arm description

Period I- Montelukast 5 mg oral tablet once daily and salmeterol matching placebo dry powder inhaler (DPI) twice daily for 4 weeks followed by a 2-week washout period (salmeterol matching placebo + montelukast matching placebo). Period II- Montelukast matching placebo oral tablet once daily and salmeterol DPI 50 mcg twice daily for 4 weeks. Inhaled fluticasone 100 mcg twice daily throughout the study.

Arm type

Experimental

Investigational medicinal product name

Montelukast sodium

Investigational medicinal product code

Other name

MK-0476

Pharmaceutical forms

Chewable tablet

Routes of administration

Oral use

Dosage and administration details

Montelukast 5 mg oral tablet once daily

Investigational medicinal product name

Salmeterol matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Matching placebo to salmeterol dry powder for inhalation administered twice daily

Investigational medicinal product name

Fluticasone propionate

Investigational medicinal product code

Other name

Flixotide Evohaler

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Fluticasone (50 mcg per actuation) 100 mcg inhaled twice daily

Salmeterol / Montelukast

Arm description

Period I- Montelukast matching placebo oral tablet once daily and salmeterol DPI 50 mcg twice daily for 4 weeks followed by a 2-week washout period (salmeterol matching placebo + montelukast matching placebo). Period II- Montelukast 5 mg oral tablet once daily and salmeterol matching placebo DPI twice daily for 4 weeks. Inhaled fluticasone 100 mcg twice daily throughout the study.

Arm type

Experimental

Investigational medicinal product name

Salmeterol xinafoate

Investigational medicinal product code

Other name

Serevent Accuhaler

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Salmeterol 50 mcg dry powder per actuation inhaled twice daily

Investigational medicinal product name

Montelukast matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Chewable tablet

Routes of administration

Oral use

Dosage and administration details

Matching placebo to montelukast oral tablet administered once daily

Investigational medicinal product name

Fluticasone propionate

Investigational medicinal product code

Other name

Flixotide Evohaler

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Fluticasone (50 mcg per actuation) 100 mcg inhaled twice daily

Number of subjects in period 1	Montelukast / Salmeterol	Salmeterol / Montelukast
Started	78	76
Completed	75	74
Not completed	3	2
Consent withdrawn by subject	2	-
Participant did not meet inclusion criteria	1	-
Protocol deviation	-	2

Period 2 title

Washout Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Subject

Are arms mutually exclusive

Yes

Montelukast / Salmeterol

Arm description

Period I- Montelukast 5 mg oral tablet once daily and Salmeterol matching placebo DPI twice daily for 4 weeks followed by a 2-week washout period (salmeterol matching placebo + montelukast matching placebo). Period II- montelukast matching placebo oral tablet once daily and Salmeterol DPI 50 mcg twice daily for 4 weeks. Inhaled Fluticasone 100 mcg twice daily throughout the study.

Arm type

Experimental

Investigational medicinal product name

Fluticasone propionate

Investigational medicinal product code

Other name

Flixotide Evohaler

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Fluticasone (50 mcg per actuation) 100 mcg inhaled twice daily

Investigational medicinal product name

Salmeterol matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Matching placebo to salmeterol dry powder for inhalation administered twice daily

Investigational medicinal product name

Montelukast matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Chewable tablet

Routes of administration

Oral use

Dosage and administration details

Matching placebo to montelukast oral tablet administered once daily

Salmeterol / Montelukast

Arm description

Period I- Montelukast matching placebo oral tablet once daily and Salmeterol DPI 50 mcg twice daily for 4 weeks followed by a 2-week washout period (salmeterol matching placebo + montelukast matching placebo). Period II- Montelukast 5 mg oral tablet once daily and Salmeterol matching placebo DPI twice daily for 4 weeks. Inhaled Fluticasone 100 mcg twice daily throughout the study.

Arm type

Experimental

Investigational medicinal product name

Fluticasone propionate

Investigational medicinal product code

Other name

Flixotide Evohaler

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Fluticasone (50 mcg per actuation) 100 mcg inhaled twice daily

Investigational medicinal product name

Salmeterol matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Matching placebo to salmeterol dry powder for inhalation administered twice daily

Investigational medicinal product name

Montelukast matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Chewable tablet

Routes of administration

Oral use

Dosage and administration details

Matching placebo to montelukast oral tablet administered once daily

Number of subjects in period 2	Montelukast / Salmeterol	Salmeterol / Montelukast
Started	75	74
Completed	75	73
Not completed	0	1
Participant did not meet inclusion criteria	-	1

Period 3 title

Period II

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Montelukast / Salmeterol

Arm description

Arm type

Experimental

Investigational medicinal product name

Montelukast matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Chewable tablet

Routes of administration

Oral use

Dosage and administration details

Matching placebo to montelukast oral tablet administered once daily

Investigational medicinal product name

Salmeterol xinafoate

Investigational medicinal product code

Other name

Serevent Accuhaler

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Salmeterol 50 mcg dry powder per actuation inhaled twice daily

Investigational medicinal product name

Fluticasone propionate

Investigational medicinal product code

Other name

Flixotide Evohaler

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Fluticasone (50 mcg per actuation) 100 mcg inhaled twice daily

Salmeterol / Montelukast

Arm description

Arm type

Experimental

Investigational medicinal product name

Montelukast sodium

Investigational medicinal product code

Other name

MK-0476

Pharmaceutical forms

Chewable tablet

Routes of administration

Oral use

Dosage and administration details

Montelukast 5 mg oral tablet once daily

Investigational medicinal product name

Salmeterol matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Matching placebo to salmeterol dry powder inhaler administered twice daily

Investigational medicinal product name

Fluticasone propionate

Investigational medicinal product code

Other name

Flixotide Evohaler

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Fluticasone (50 mcg per actuation) 100 mcg inhaled twice daily

Number of subjects in period 3	Montelukast / Salmeterol	Salmeterol / Montelukast
Started	75	73
Completed	72	73
Not completed	3	0
Consent withdrawn by subject	2	-
Participant did not perform last visit exercise	1	-

Baseline characteristics

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Reporting group title

Montelukast / Salmeterol

Reporting group description

Reporting group title

Salmeterol / Montelukast

Reporting group description

Reporting group values	Montelukast / Salmeterol	Salmeterol / Montelukast	Total
Number of subjects	78	76	154
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	10.2 ± 2	9.8 ± 2	-
Gender categorical
Units: Subjects
Female	35	30	65
Male	43	46	89
Race
Units: Subjects
Asian	1	0	1
Black	11	7	18
White	38	41	79
Hispanic	15	18	33
Multiracial	13	10	23
Area under the curve from 0 to 20 minutes (AUC(0-20))
Area Under the Curve for percent-change from pre-exercise baseline FEV1 in liters, from 0 to 20 minutes (AUC(0-20))
Units: Percent times minutes
arithmetic mean (standard deviation)	320.08 ± 208.62	317.74 ± 165.71	-
Avg %-change from pre-exercise baseline FEV1 after 1st β-agonist use & Prior to 2nd β-agonist use
Average (avg) percent (%)-change from pre-exercise baseline FEV1 after 1st β-agonist use & prior to 2nd β-agonist use
Units: Percent change from baseline
arithmetic mean (standard deviation)	1.36 ± 10.99	4.78 ± 10.92	-
Maximum FEV1 Percent Predicted
Units: Percent of predicted value
arithmetic mean (standard deviation)	99.88 ± 32.45	100.54 ± 15.61	-
Maximum Percent Fall in FEV1 After Exercise
Units: Percent change from baseline
arithmetic mean (standard deviation)	24.77 ± 10.25	25.42 ± 9.04	-
Time to recovery
Population includes participants who returned to within 5% of the baseline FEV1 value. Montelukast / Salmeterol, n=71; Salmeterol / Montelukast, n=70
Units: Minutes
arithmetic mean (standard deviation)	23.53 ± 10.53	21.51 ± 8.3	-

End points

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Reporting group title

Montelukast / Salmeterol

Reporting group description

Reporting group title

Salmeterol / Montelukast

Reporting group description

Reporting group title

Montelukast / Salmeterol

Reporting group description

Reporting group title

Salmeterol / Montelukast

Reporting group description

Reporting group title

Montelukast / Salmeterol

Reporting group description

Reporting group title

Salmeterol / Montelukast

Reporting group description

Subject analysis set title

Montelukast

Subject analysis set type

Full analysis

Subject analysis set description

The primary efficacy analysis was based on the full analysis set (FAS) population which included all randomized participants who took at least one dose of post randomization study drug and had a measurement for analysis available in both treatment periods of the cross-over design.

Subject analysis set title

Salmeterol

Subject analysis set type

Full analysis

Subject analysis set description

Primary: Maximum post-exercise percent fall in FEV1

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End point title

Maximum post-exercise percent fall in FEV1

End point description

The effect of four weeks of treatment with oral montelukast plus inhaled fluticasone, and inhaled salmeterol plus inhaled fluticasone on EIB as measured by the maximum post-exercise percent fall (relative to pre-exercise baseline) in FEV1.

End point type

Primary

End point timeframe

4 weeks (Weeks 0 to 4 or Weeks 6 to 10)

End point values	Montelukast	Salmeterol
Number of subjects analysed	144	144
Units: Percent change from baseline
least squares mean (confidence interval 95%)	10.57 (8.86 to 12.27)	13.82 (12.11 to 15.52)

Difference in least squares mean

Statistical analysis description

There were a total of 144 participants included in this analysis (cross-over design).

Comparison groups

Montelukast v Salmeterol

Number of subjects included in analysis

288

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.009 ^[1]

Method

ANOVA

Parameter type

Least squares mean difference

Point estimate

-3.25

Confidence interval

level

95%

sides

2-sided

lower limit

-5.66

upper limit

-0.84

Notes
[1] - Model terms: participant, treatment and period. The treatment test is adjusted for period.

Secondary: Area under the curve for percent-change from pre-exercise baseline FEV1 in liters, from 0 to 20 Minutes (AUC(0-20))

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End point title

Area under the curve for percent-change from pre-exercise baseline FEV1 in liters, from 0 to 20 Minutes (AUC(0-20))

End point description

The effect of a four-week treatment course of oral montelukast plus inhaled fluticasone, compared to inhaled salmeterol plus inhaled fluticasone, on the extent and severity of EIB as measured by the area under the curve from 0 to 20 minutes (AUC0-20) for FEV1 percent change from pre-exercise baseline.

End point type

Secondary

End point timeframe

4 weeks (Weeks 0 to 4 or Weeks 6 to 10)

End point values	Montelukast	Salmeterol
Number of subjects analysed	144	144
Units: Percent times minutes
least squares mean (confidence interval 95%)	116.04 (89.95 to 142.24)	168.75 (142.56 to 194.95)

Difference in least squares mean

Statistical analysis description

There were a total of 144 participants included in this analysis (cross-over design).

Comparison groups

Montelukast v Salmeterol

Number of subjects included in analysis

288

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.006 ^[2]

Method

ANOVA

Parameter type

Least squares mean difference

Point estimate

-52.71

Confidence interval

level

95%

sides

2-sided

lower limit

-89.76

upper limit

-15.66

Notes
[2] - Model terms: participant, treatment and period. The treatment test is adjusted for period.

Secondary: Maximum FEV1 percent predicted following first β-agonist use

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End point title

Maximum FEV1 percent predicted following first β-agonist use

End point description

The effect of a four-week treatment course of oral montelukast plus inhaled fluticasone, compared to inhaled salmeterol plus inhaled fluticasone, on short-acting β-agonist bronchodilation as measured by the maximum FEV1 percent predicted following first β-agonist use.

End point type

Secondary

End point timeframe

4 weeks (Weeks 0 to 4 or Weeks 6 to 10)

End point values	Montelukast	Salmeterol
Number of subjects analysed	144	144
Units: Percent of predicted value
least squares mean (confidence interval 95%)	104.03 (102.83 to 105.23)	99.92 (98.72 to 101.12)

Difference in least squares mean

Statistical analysis description

There were a total of 144 participants included in this analysis (cross-over design).

Comparison groups

Montelukast v Salmeterol

Number of subjects included in analysis

288

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[3]

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

4.11

Confidence interval

level

95%

sides

2-sided

lower limit

2.58

upper limit

5.64

Notes
[3] - Terms: participant, treatment, period & covariate for FEV1 %-predicted at pre-exercise baseline.

Secondary: Time to recovery to within 5 percent of baseline FEV1

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End point title

Time to recovery to within 5 percent of baseline FEV1

End point description

The effect of a four-week treatment course of oral montelukast plus inhaled fluticasone, compared to inhaled salmeterol plus inhaled fluticasone, on the extent and severity of EIB as measured by the time to recovery (to within 5 percent of the pre-exercise baseline FEV1) following a standardized exercise challenge.

End point type

Secondary

End point timeframe

4 weeks (Weeks 0 to 4 or Weeks 6 to 10)

End point values	Montelukast	Salmeterol
Number of subjects analysed	144	144
Units: minutes
median (inter-quartile range (Q1-Q3))	5.9 (0 to 19.12)	11.1 (0.065 to 22.94)

Comparison between montelukast vs. salmeterol

Statistical analysis description

There were a total of 144 participants included in this analysis (cross-over design).

Comparison groups

Montelukast v Salmeterol

Number of subjects included in analysis

288

Analysis specification

Pre-specified

Analysis type

other ^[4]

P-value

= 0.035 ^[5]

Method

Cox proportional hazard model

Parameter type

Hazard ratio (HR)

Point estimate

1.26

Confidence interval

level

95%

sides

2-sided

lower limit

1.02

upper limit

1.55

Notes
[4] - A robust estimate of the variance of the treatment effect was calculated using the marginal approach introduced by Wei, Lin and Weissfeld (WLW model).
[5] - Model terms: treatment and period.

Secondary: Average percent-change in FEV1 after first β-agonist use and prior to second β-agonist use

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End point title

Average percent-change in FEV1 after first β-agonist use and prior to second β-agonist use

End point description

The effect of a four-week treatment course of oral montelukast plus inhaled fluticasone, compared to inhaled salmeterol plus inhaled fluticasone, on the extent and severity of EIB as measured by the average percent change in FEV1 after first β-agonist intake and prior to second β-agonist use.

End point type

Secondary

End point timeframe

4 weeks (Weeks 0 to 4 or Weeks 6 to 10)

End point values	Montelukast	Salmeterol
Number of subjects analysed	144	144
Units: Percent change from baseline
least squares mean (confidence interval 95%)	6.51 (5.44 to 7.59)	2.72 (1.64 to 3.79)

Difference in least squares mean

Statistical analysis description

There were a total of 144 participants included in this analysis (cross-over design).

Comparison groups

Montelukast v Salmeterol

Number of subjects included in analysis

288

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[6]

Method

ANOVA

Parameter type

Least squares mean difference

Point estimate

3.8

Confidence interval

level

95%

sides

2-sided

lower limit

2.28

upper limit

5.32

Notes
[6] - Model terms: participant, treatment and period. The treatment test is adjusted for period.

Adverse events

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Timeframe for reporting adverse events

Up to 12 weeks (including 2 weeks following last dose of study drug)

Adverse event reporting additional description

Of 154 participants enrolled, only 150 took at least 1 dose of each treatment (tx); 78 were in Montelukast (M) /Salmeterol (S) sequence (seq) and 76 in S/M seq. 4 participants in M/S seq only took 1st tx; so 78 took M & 74 took S. 4 different participants in S/M seq only took 1st tx; so 76 took S & 72 took M. Total 150 pts took M and 150 took S.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

11.1

Reporting group title

Montelukast

Reporting group description

Period I- Montelukast 5 mg oral tablet once daily and Salmeterol matching placebo DPI twice daily for 4 weeks. Period II- Montelukast 5 mg oral tablet once daily and Salmeterol matching placebo DPI twice daily for 4 weeks. Inhaled Fluticasone 100 mcg twice daily throughout the study.

Reporting group title

Salmeterol

Reporting group description

Period I- Montelukast matching placebo oral tablet once daily and Salmeterol DPI 50 mcg twice daily for 4 weeks. Period II- Montelukast matching placebo oral tablet once daily and Salmeterol DPI 50 mcg twice daily for 4 weeks. Inhaled Fluticasone 100 mcg twice daily throughout the study.

Serious adverse events	Montelukast	Salmeterol
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 150 (0.67%)	1 / 150 (0.67%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Accidental overdose
subjects affected / exposed	0 / 150 (0.00%)	1 / 150 (0.67%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Overdose
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Montelukast	Salmeterol
Total subjects affected by non serious adverse events
subjects affected / exposed	27 / 150 (18.00%)	21 / 150 (14.00%)
Injury, poisoning and procedural complications
Ear injury
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences all number	1	0
Fall
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences all number	1	0
Limb injury
subjects affected / exposed	1 / 150 (0.67%)	1 / 150 (0.67%)
occurrences all number	1	1
Skin injury
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences all number	1	0
Wound
subjects affected / exposed	0 / 150 (0.00%)	1 / 150 (0.67%)
occurrences all number	0	1
Nervous system disorders
Headache
subjects affected / exposed	2 / 150 (1.33%)	0 / 150 (0.00%)
occurrences all number	2	0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 150 (0.00%)	2 / 150 (1.33%)
occurrences all number	0	2
Immune system disorders
Allergy to plants
subjects affected / exposed	0 / 150 (0.00%)	1 / 150 (0.67%)
occurrences all number	0	1
Eye disorders
Conjunctivitis
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences all number	1	0
Conjunctivitis allergic
subjects affected / exposed	0 / 150 (0.00%)	1 / 150 (0.67%)
occurrences all number	0	1
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	2 / 150 (1.33%)	0 / 150 (0.00%)
occurrences all number	2	0
Toothache
subjects affected / exposed	0 / 150 (0.00%)	1 / 150 (0.67%)
occurrences all number	0	1
Reproductive system and breast disorders
Menstruation delayed
subjects affected / exposed	0 / 150 (0.00%)	1 / 150 (0.67%)
occurrences all number	0	1
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	4 / 150 (2.67%)	4 / 150 (2.67%)
occurrences all number	4	4
Bronchospasm
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences all number	1	0
Nasal congestion
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences all number	1	0
Wheezing
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences all number	1	0
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences all number	1	0
Eczema
subjects affected / exposed	1 / 150 (0.67%)	1 / 150 (0.67%)
occurrences all number	1	1
Skin lesion
subjects affected / exposed	0 / 150 (0.00%)	1 / 150 (0.67%)
occurrences all number	0	1
Infections and infestations
Candidiasis
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences all number	1	0
Ear infection
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences all number	1	0
Influenza
subjects affected / exposed	1 / 150 (0.67%)	1 / 150 (0.67%)
occurrences all number	1	1
Nasopharyngitis
subjects affected / exposed	2 / 150 (1.33%)	1 / 150 (0.67%)
occurrences all number	2	1
Pertussis
subjects affected / exposed	2 / 150 (1.33%)	0 / 150 (0.00%)
occurrences all number	2	0
Pharyngitis
subjects affected / exposed	5 / 150 (3.33%)	3 / 150 (2.00%)
occurrences all number	5	3
Pneumonia
subjects affected / exposed	0 / 150 (0.00%)	1 / 150 (0.67%)
occurrences all number	0	1
Respiratory tract infection
subjects affected / exposed	0 / 150 (0.00%)	1 / 150 (0.67%)
occurrences all number	0	1
Respiratory tract infection viral
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences all number	1	0
Tonsillitis
subjects affected / exposed	3 / 150 (2.00%)	2 / 150 (1.33%)
occurrences all number	3	2
Upper respiratory tract infection
subjects affected / exposed	1 / 150 (0.67%)	1 / 150 (0.67%)
occurrences all number	1	1
Viral infection
subjects affected / exposed	0 / 150 (0.00%)	2 / 150 (1.33%)
occurrences all number	0	2
Viral pharyngitis
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences all number	1	0
Viral rhinitis
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences all number	1	0

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Were there any global substantial amendments to the protocol? Yes

13 Aug 2005

Amendment 1: Primary reason for the amendment was to update the salmeterol dosage to salmeterol/matching placebo drug powder inhaler (DPI) formulation 50 mcg/puff, one puff twice daily, total dose of 100 mcg/day. Use of spacer device with salmeterol was deleted.

16 Jan 2007

Amendment 2: Primary reason for the amendment was that participants must demonstrate exercise induced bronchoconstriction with post-exercise decline in FEV1 of 15 % (change from 20 %).

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A Multicenter, Double-Blind, Randomized, Cross-Over Design Study to Evaluate the Effect of Montelukast vs. Salmeterol on the Inhibition of Exercise-Induced Bronchoconstriction in Asthmatic Patients Aged 6-14 Years.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Maximum post-exercise percent fall in FEV1

Primary: Maximum post-exercise percent fall in FEV1

Secondary: Area under the curve for percent-change from pre-exercise baseline FEV1 in liters, from 0 to 20 Minutes (AUC(0-20))

Secondary: Area under the curve for percent-change from pre-exercise baseline FEV1 in liters, from 0 to 20 Minutes (AUC(0-20))

Secondary: Maximum FEV1 percent predicted following first β-agonist use

Secondary: Maximum FEV1 percent predicted following first β-agonist use

Secondary: Time to recovery to within 5 percent of baseline FEV1

Secondary: Time to recovery to within 5 percent of baseline FEV1

Secondary: Average percent-change in FEV1 after first β-agonist use and prior to second β-agonist use

Secondary: Average percent-change in FEV1 after first β-agonist use and prior to second β-agonist use

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
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Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Multicenter, Double-Blind, Randomized, Cross-Over Design Study to Evaluate the Effect of Montelukast vs. Salmeterol on the Inhibition of Exercise-Induced Bronchoconstriction in Asthmatic Patients Aged 6-14 Years.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Maximum post-exercise percent fall in FEV1

Primary: Maximum post-exercise percent fall in FEV1

Secondary: Area under the curve for percent-change from pre-exercise baseline FEV1 in liters, from 0 to 20 Minutes (AUC(0-20))

Secondary: Area under the curve for percent-change from pre-exercise baseline FEV1 in liters, from 0 to 20 Minutes (AUC(0-20))

Secondary: Maximum FEV1 percent predicted following first β-agonist use

Secondary: Maximum FEV1 percent predicted following first β-agonist use

Secondary: Time to recovery to within 5 percent of baseline FEV1

Secondary: Time to recovery to within 5 percent of baseline FEV1

Secondary: Average percent-change in FEV1 after first β-agonist use and prior to second β-agonist use

Secondary: Average percent-change in FEV1 after first β-agonist use and prior to second β-agonist use

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Multicenter, Double-Blind, Randomized, Cross-Over Design Study to Evaluate the Effect of Montelukast vs. Salmeterol on the Inhibition of Exercise-Induced Bronchoconstriction in Asthmatic Patients Aged 6-14 Years.