Montelukast Compared With Placebo and Salmeterol in Exercise-Induced Bronchoconstriction (0476-316)

Sponsor
Organon and Co (Industry)
Overall Status
Completed
CT.gov ID
NCT00245570
Collaborator
(none)
47
6
9

Study Details

Study Description

Brief Summary

To determine the effect of an approved medication being studied in support of a new approach in the prevention of exercise-induced asthma (a worsening of asthma caused by exercise, also known as exercise-induced bronchospasm), in patients who have a history of worsening asthma after exercise.

Condition or Disease Intervention/Treatment Phase
  • Drug: Comparator: Montelukast
  • Drug: Comparator: Salmeterol
  • Drug: Comparator: Placebo (montelukast)
  • Drug: Comparator: Placebo (salmeterol)
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
47 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
A Double-Blind, Randomized Multicenter, 3-Period, Crossover Study to Evaluate the Effects of a Single Dose of Montelukast Compared With Placebo and Salmeterol on Exercise-Induced Bronchoconstriction
Study Start Date :
Dec 1, 2005
Actual Primary Completion Date :
Sep 1, 2006
Actual Study Completion Date :
Sep 1, 2006

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

Montelukast - Salmeterol - Placebo

Drug: Comparator: Montelukast
1 dose montelukast 10 mg tablet given orally in one of three treatment periods

Drug: Comparator: Salmeterol
1 dose of 50 ug salmeterol given by inhalation in one of three treatment periods

Drug: Comparator: Placebo (montelukast)
1 dose matching-image placebo to montelukast tablet in two of three treatment periods

Drug: Comparator: Placebo (salmeterol)
1 dose matching-image placebo of salmeterol 50 ug inhalation in two of three treatment periods

Experimental: 2

Montelukast - Placebo - Salmeterol

Drug: Comparator: Montelukast
1 dose montelukast 10 mg tablet given orally in one of three treatment periods

Drug: Comparator: Salmeterol
1 dose of 50 ug salmeterol given by inhalation in one of three treatment periods

Drug: Comparator: Placebo (montelukast)
1 dose matching-image placebo to montelukast tablet in two of three treatment periods

Drug: Comparator: Placebo (salmeterol)
1 dose matching-image placebo of salmeterol 50 ug inhalation in two of three treatment periods

Experimental: 3

Salmeterol - Montelukast - Placebo

Drug: Comparator: Montelukast
1 dose montelukast 10 mg tablet given orally in one of three treatment periods

Drug: Comparator: Salmeterol
1 dose of 50 ug salmeterol given by inhalation in one of three treatment periods

Drug: Comparator: Placebo (montelukast)
1 dose matching-image placebo to montelukast tablet in two of three treatment periods

Drug: Comparator: Placebo (salmeterol)
1 dose matching-image placebo of salmeterol 50 ug inhalation in two of three treatment periods

Experimental: 4

Salmeterol - Placebo - Montelukast

Drug: Comparator: Montelukast
1 dose montelukast 10 mg tablet given orally in one of three treatment periods

Drug: Comparator: Salmeterol
1 dose of 50 ug salmeterol given by inhalation in one of three treatment periods

Drug: Comparator: Placebo (montelukast)
1 dose matching-image placebo to montelukast tablet in two of three treatment periods

Drug: Comparator: Placebo (salmeterol)
1 dose matching-image placebo of salmeterol 50 ug inhalation in two of three treatment periods

Experimental: 5

Placebo - Montelukast - Salmeterol

Drug: Comparator: Montelukast
1 dose montelukast 10 mg tablet given orally in one of three treatment periods

Drug: Comparator: Salmeterol
1 dose of 50 ug salmeterol given by inhalation in one of three treatment periods

Drug: Comparator: Placebo (montelukast)
1 dose matching-image placebo to montelukast tablet in two of three treatment periods

Drug: Comparator: Placebo (salmeterol)
1 dose matching-image placebo of salmeterol 50 ug inhalation in two of three treatment periods

Experimental: 6

Placebo - Salmeterol - Montelukast

Drug: Comparator: Montelukast
1 dose montelukast 10 mg tablet given orally in one of three treatment periods

Drug: Comparator: Salmeterol
1 dose of 50 ug salmeterol given by inhalation in one of three treatment periods

Drug: Comparator: Placebo (montelukast)
1 dose matching-image placebo to montelukast tablet in two of three treatment periods

Drug: Comparator: Placebo (salmeterol)
1 dose matching-image placebo of salmeterol 50 ug inhalation in two of three treatment periods

Outcome Measures

Primary Outcome Measures

  1. Maximum Percent Fall in Forced Expiratory Volume in 1 Second (FEV1) After Exercise Challenge at 2 Hours Post-dose in Patients With Exercise-Induced Bronchoconstriction (EIB) [0-60 minutes after the exercise challenge performed 2 hours after a single oral dose]

    In patients with EIB, the percent change from pre-exercise baseline FEV1 to the lowest FEV1 within 60 minutes after exercise challenge (2 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge.

Secondary Outcome Measures

  1. Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose [0-90 minutes after the exercise challenge performed at 2 hours postdose]

  2. Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 8.5 Hours Postdose [0-90 minutes after the exercise challenge performed at 8.5 hours postdose]

  3. Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose [0-90 minutes after the exercise challenge performed at 24 hours postdose]

  4. Maximum Percent Fall in FEV1 After Exercise Challenge at 8.5 Hours Post-dose in Patients With EIB [0-60 minutes after the exercise challenge performed 8.5 hours after a single oral dose]

    In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (8.5 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge.

  5. Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Post-dose in Patients With EIB [0-60 minutes after the exercise challenge performed 24 hours after a single oral dose]

    In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (24 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge.

  6. Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 2 Hours Postdose [0-60 minutes after the exercise challenge at 2 hours postdose]

    The measure included only the area below the pre-exercise baseline

  7. Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 8.5 Hours Postdose [0-60 minutes after the exercise challenge at 8.5 hours postdose]

    The measure included only the area below the pre-exercise baseline

  8. Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 24 Hours Postdose [0-60 minutes after the exercise challenge at 24 hours postdose]

    The measure included only the area below the pre-exercise baseline

  9. Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 2 Hours Postdose [Exercise challenge at 2 hours postdose]

    The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.

  10. Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 8.5 Hours Postdose [Exercise challenge at 8.5 hours postdose]

    The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.

  11. Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 24 Hours Postdose [Exercise challenge at 24 hours postdose]

    The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.

Eligibility Criteria

Criteria

Ages Eligible for Study:
15 Years to 45 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Physician-diagnosed exercise-induced bronchospasm
Exclusion Criteria:
  • Patient is, other than asthma, not in good, stable health. The Primary Investigator will evaluate whether there are other reasons why the patient may not participate.

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

Responsible Party:
Organon and Co
ClinicalTrials.gov Identifier:
NCT00245570
Other Study ID Numbers:
  • 0476-316
  • MK0476-316
  • 2005_043
First Posted:
Oct 28, 2005
Last Update Posted:
Feb 2, 2022
Last Verified:
Jan 1, 2022

Study Results

Participant Flow

Recruitment Details Patients were randomized at 5 sites (4 in the US and 1 in Peru). Primary therapy period: December 2005 to August 2006
Pre-assignment Detail Patients who required excluded medications, or did not meet FEV1 criteria during the prestudy period were excluded from randomization.
Arm/Group Title Montelukast/ Salmeterol/Placebo Montelukast/ Placebo/ Salmeterol Salmeterol / Montelukast/ Placebo Salmeterol/ Placebo/ Montelukast Placebo/ Montelukast/ Salmeterol Placebo/ Salmeterol/ Montelukast
Arm/Group Description During Period I (placebo run-in), all patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period II, patients received a single witnessed dose of montelukast 10-mg oral tablet and salmeterol matching-image placebo inhalation powder. Washout 1 (Washout between Periods II and III) 3- to 7-day washout between Periods II and III. During Period III, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol 50-μg inhalation powder. Washout 2 (Washout between Periods III and IV) 3- to 7-day washout between Periods III and IV. During Period IV, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period I (placebo run-in), all patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period II, patients received a single witnessed dose of montelukast 10-mg oral tablet and salmeterol matching-image placebo inhalation powder. Washout 1 (Washout between Periods II and III) 3- to 7-day washout between Periods II and III. During Period III, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. Washout 2 (Washout between Periods III and IV) 3- to 7-day washout between Periods III and IV. During Period IV, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol 50-μg inhalation powder. During Period I (placebo run-in), all patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period II, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol 50-μg inhalation powder. Washout 1 (Washout between Periods II and III) 3- to 7-day washout between Periods II and III. During Period III, patients received a single witnessed dose of montelukast 10-mg oral tablet and salmeterol matching-image placebo inhalation powder. Washout 2 (Washout between Periods III and IV) 3- to 7-day washout between Periods III and IV. During Period IV, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period I (placebo run-in), all patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period II, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol 50-μg inhalation powder. Washout 1 (Washout between Periods II and III) 3- to 7-day washout between Periods II and III. During Period III, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. Washout 2 (Washout between Periods III and IV) 3- to 7-day washout between Periods III and IV. During Period IV, patients received a single witnessed dose of montelukast 10-mg oral tablet and salmeterol matching-image placebo inhalation powder. During Period I (placebo run-in), all patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period II, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. Washout 1 (Washout between Periods II and III) 3- to 7-day washout between Periods II and III. During Period III, patients received a single witnessed dose of montelukast 10-mg oral tablet and salmeterol matching-image placebo inhalation powder. Washout 2 (Washout between Periods III and IV) 3- to 7-day washout between Periods III and IV. During Period IV, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol 50-μg inhalation powder. During Period I (placebo run-in), all patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period II, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. Washout 1 (Washout between Periods II and III) 3- to 7-day washout between Periods II and III. During Period III, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol 50-μg inhalation powder. Washout 2 (Washout between Periods III and IV) 3- to 7-day washout between Periods III and IV. During Period IV, patients received a single witnessed dose of montelukast 10-mg oral tablet and salmeterol matching-image placebo inhalation powder.
Period Title: Treatment Period II
STARTED 7 8 8 8 8 8
COMPLETED 7 8 8 8 8 8
NOT COMPLETED 0 0 0 0 0 0
Period Title: Treatment Period II
STARTED 7 8 8 8 8 8
COMPLETED 7 8 8 8 8 8
NOT COMPLETED 0 0 0 0 0 0
Period Title: Treatment Period II
STARTED 7 8 8 8 8 8
COMPLETED 7 8 8 8 8 8
NOT COMPLETED 0 0 0 0 0 0
Period Title: Treatment Period II
STARTED 7 8 8 8 8 8
COMPLETED 7 7 8 8 8 8
NOT COMPLETED 0 1 0 0 0 0
Period Title: Treatment Period II
STARTED 7 7 8 8 8 8
COMPLETED 7 7 8 8 8 8
NOT COMPLETED 0 0 0 0 0 0

Baseline Characteristics

Arm/Group Title Overall Study Population
Arm/Group Description All randomized patients
Overall Participants 47
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
26.0
(7.92)
Sex: Female, Male (Count of Participants)
Female
24
51.1%
Male
23
48.9%
Need for β-agonist rescue medication following exercise challenge (participants) [Number]
No
31
66%
Yes
16
34%
Area under the FEV1 percent change from baseline time curve for 0-60 mins after exercise challenge (% * minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% * minutes]
957.46
(518.69)
Maximum percent fall in forced expiratory volume in 1 second (FEV1) post-exercise challenge (Percent Change from Baseline) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent Change from Baseline]
27.75
(6.26)
Time to recovery from maximal percent fall (Minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Minutes]
55.03
(32.62)

Outcome Measures

1. Primary Outcome
Title Maximum Percent Fall in Forced Expiratory Volume in 1 Second (FEV1) After Exercise Challenge at 2 Hours Post-dose in Patients With Exercise-Induced Bronchoconstriction (EIB)
Description In patients with EIB, the percent change from pre-exercise baseline FEV1 to the lowest FEV1 within 60 minutes after exercise challenge (2 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge.
Time Frame 0-60 minutes after the exercise challenge performed 2 hours after a single oral dose

Outcome Measure Data

Analysis Population Description
The primary efficacy analysis used the modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
Arm/Group Title Montelukast 10 mg Salmeterol 50-μg Placebo
Arm/Group Description All Montelukast 10 mg patients from all Treatment Periods. All Salmeterol 50-μg patients from all Treatment Periods. All Placebo patients from all Treatment Periods.
Measure Participants 47 46 47
Mean (Standard Deviation) [Percent Change from Baseline]
13.15
(10.28)
10.46
(9.95)
21.86
(13.44)
2. Secondary Outcome
Title Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose
Description
Time Frame 0-90 minutes after the exercise challenge performed at 2 hours postdose

Outcome Measure Data

Analysis Population Description
The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
Arm/Group Title Montelukast 10 mg Salmeterol 50-μg Placebo
Arm/Group Description All Montelukast 10 mg patients from all Treatment Periods. All Salmeterol 50-μg patients from all Treatment Periods. All Placebo patients from all Treatment Periods.
Measure Participants 47 46 47
Patients Requiring Rescue Medication
3
6.4%
4
NaN
9
NaN
Patients Not Requiring Rescue Medication
44
93.6%
42
NaN
38
NaN
3. Secondary Outcome
Title Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 8.5 Hours Postdose
Description
Time Frame 0-90 minutes after the exercise challenge performed at 8.5 hours postdose

Outcome Measure Data

Analysis Population Description
The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
Arm/Group Title Montelukast 10 mg Salmeterol 50-μg Placebo
Arm/Group Description All Montelukast 10 mg patients from all Treatment Periods. All Salmeterol 50-μg patients from all Treatment Periods. All Placebo patients from all Treatment Periods.
Measure Participants 40 39 37
Patients Requiring Rescue Medication
0
0%
0
NaN
4
NaN
Patients Not Requiring Rescue Medication
40
85.1%
39
NaN
33
NaN
4. Secondary Outcome
Title Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose
Description
Time Frame 0-90 minutes after the exercise challenge performed at 24 hours postdose

Outcome Measure Data

Analysis Population Description
The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
Arm/Group Title Montelukast 10 mg Salmeterol 50-μg Placebo
Arm/Group Description All Montelukast 10 mg patients from all Treatment Periods. All Salmeterol 50-μg patients from all Treatment Periods. All Placebo patients from all Treatment Periods.
Measure Participants 46 46 46
Patients Requiring Rescue Medication
3
6.4%
6
NaN
6
NaN
Patients Not Requiring Rescue Medication
43
91.5%
40
NaN
40
NaN
5. Secondary Outcome
Title Maximum Percent Fall in FEV1 After Exercise Challenge at 8.5 Hours Post-dose in Patients With EIB
Description In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (8.5 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge.
Time Frame 0-60 minutes after the exercise challenge performed 8.5 hours after a single oral dose

Outcome Measure Data

Analysis Population Description
The secondary efficacy analysis used the modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
Arm/Group Title Montelukast 10 mg Salmeterol 50-μg Placebo
Arm/Group Description All Montelukast 10 mg patients from all Treatment Periods. All Salmeterol 50-μg patients from all Treatment Periods. All Placebo patients from all Treatment Periods.
Measure Participants 40 39 37
Mean (Standard Deviation) [Percent Change from Baseline]
11.60
(9.64)
11.01
(7.56)
16.65
(12.76)
6. Secondary Outcome
Title Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Post-dose in Patients With EIB
Description In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (24 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge.
Time Frame 0-60 minutes after the exercise challenge performed 24 hours after a single oral dose

Outcome Measure Data

Analysis Population Description
The secondary efficacy analysis used the modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
Arm/Group Title Montelukast 10 mg Salmeterol 50-μg Placebo
Arm/Group Description All Montelukast 10 mg patients from all Treatment Periods. All Salmeterol 50-μg patients from all Treatment Periods. All Placebo patients from all Treatment Periods.
Measure Participants 46 46 46
Mean (Standard Deviation) [Percent Change from Baseline]
10.09
(11.10)
16.22
(13.09)
13.64
(9.67)
7. Secondary Outcome
Title Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 2 Hours Postdose
Description The measure included only the area below the pre-exercise baseline
Time Frame 0-60 minutes after the exercise challenge at 2 hours postdose

Outcome Measure Data

Analysis Population Description
The secondary efficacy analysis used a MITT approach. If a patient received β-agonist rescue medication during the 60 minutes following exercise challenge, then the last pre-rescue FEV1 measurement was carried forward to 60 minutes. Patients with data from only one period were not included in the analysis.
Arm/Group Title Montelukast 10 mg Salmeterol 50-μg Placebo
Arm/Group Description All Montelukast 10 mg patients from all Treatment Periods. All Salmeterol 50-μg patients from all Treatment Periods. All Placebo patients from all Treatment Periods.
Measure Participants 47 46 47
Mean (Standard Deviation) [Percent * minutes]
254.60
(241.17)
293.05
(362.33)
710.43
(529.91)
8. Secondary Outcome
Title Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 8.5 Hours Postdose
Description The measure included only the area below the pre-exercise baseline
Time Frame 0-60 minutes after the exercise challenge at 8.5 hours postdose

Outcome Measure Data

Analysis Population Description
The secondary efficacy analysis used a MITT approach. If a patient received β-agonist rescue medication during the 60 minutes following exercise challenge, then the last pre-rescue FEV1 measurement was carried forward to 60 minutes. Patients with data from only one period were not included in the analysis.
Arm/Group Title Montelukast 10 mg Salmeterol 50-μg Placebo
Arm/Group Description All Montelukast 10 mg patients from all Treatment Periods. All Salmeterol 50-μg patients from all Treatment Periods. All Placebo patients from all Treatment Periods.
Measure Participants 40 39 37
Mean (Standard Deviation) [Percent * minutes]
191.01
(166.24)
276.26
(226.37)
511.28
(566.30)
9. Secondary Outcome
Title Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 24 Hours Postdose
Description The measure included only the area below the pre-exercise baseline
Time Frame 0-60 minutes after the exercise challenge at 24 hours postdose

Outcome Measure Data

Analysis Population Description
The secondary efficacy analysis used a MITT approach. If a patient received β-agonist rescue medication during the 60 minutes following exercise challenge, then the last pre-rescue FEV1 measurement was carried forward to 60 minutes. Patients with data from only one period were not included in the analysis.
Arm/Group Title Montelukast 10 mg Salmeterol 50-μg Placebo
Arm/Group Description All Montelukast 10 mg patients from all Treatment Periods. All Salmeterol 50-μg patients from all Treatment Periods. All Placebo patients from all Treatment Periods.
Measure Participants 46 46 46
Mean (Standard Deviation) [Percent * minutes]
231.09
(413.73)
554.93
(649.52)
395.96
(464.92)
10. Secondary Outcome
Title Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 2 Hours Postdose
Description The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.
Time Frame Exercise challenge at 2 hours postdose

Outcome Measure Data

Analysis Population Description
The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
Arm/Group Title Montelukast 10 mg Salmeterol 50-μg Placebo
Arm/Group Description All Montelukast 10 mg patients from all Treatment Periods. All Salmeterol 50-μg patients from all Treatment Periods. All Placebo patients from all Treatment Periods.
Measure Participants 47 46 47
Mean (Standard Deviation) [Minutes]
16.63
(23.72)
17.58
(27.81)
42.70
(34.26)
11. Secondary Outcome
Title Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 8.5 Hours Postdose
Description The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.
Time Frame Exercise challenge at 8.5 hours postdose

Outcome Measure Data

Analysis Population Description
The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
Arm/Group Title Montelukast 10 mg Salmeterol 50-μg Placebo
Arm/Group Description All Montelukast 10 mg patients from all Treatment Periods. All Salmeterol 50-μg patients from all Treatment Periods. All Placebo patients from all Treatment Periods.
Measure Participants 40 39 37
Mean (Standard Deviation) [Minutes]
10.70
(13.38)
13.82
(18.37)
32.34
(34.57)
12. Secondary Outcome
Title Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 24 Hours Postdose
Description The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.
Time Frame Exercise challenge at 24 hours postdose

Outcome Measure Data

Analysis Population Description
The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.
Arm/Group Title Montelukast 10 mg Salmeterol 50-μg Placebo
Arm/Group Description All Montelukast 10 mg patients from all Treatment Periods. All Salmeterol 50-μg patients from all Treatment Periods. All Placebo patients from all Treatment Periods.
Measure Participants 46 46 46
Mean (Standard Deviation) [Minutes]
11.04
(20.84)
29.75
(33.50)
23.31
(29.30)

Adverse Events

Time Frame Periods II through IV and washout periods in between these treatment periods, and up to and including 14 days after the last dose of study therapy.
Adverse Event Reporting Description Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories.
Arm/Group Title Montelukast/ Salmeterol/Placebo Montelukast/ Placebo/ Salmeterol Salmeterol / Montelukast/ Placebo Salmeterol/ Placebo/ Montelukast Placebo/ Montelukast/ Salmeterol Placebo/ Salmeterol/ Montelukast
Arm/Group Description During Period I (placebo run-in), all patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period II, patients received a single witnessed dose of montelukast 10-mg oral tablet and salmeterol matching-image placebo inhalation powder. Washout 1 (Washout between Periods II and III) 3- to 7-day washout between Periods II and III. During Period III, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol 50-μg inhalation powder. Washout 2 (Washout between Periods III and IV) 3- to 7-day washout between Periods III and IV. During Period IV, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period I (placebo run-in), all patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period II, patients received a single witnessed dose of montelukast 10-mg oral tablet and salmeterol matching-image placebo inhalation powder. Washout 1 (Washout between Periods II and III) 3- to 7-day washout between Periods II and III. During Period III, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. Washout 2 (Washout between Periods III and IV) 3- to 7-day washout between Periods III and IV. During Period IV, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol 50-μg inhalation powder. During Period I (placebo run-in), all patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period II, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol 50-μg inhalation powder. Washout 1 (Washout between Periods II and III) 3- to 7-day washout between Periods II and III. During Period III, patients received a single witnessed dose of montelukast 10-mg oral tablet and salmeterol matching-image placebo inhalation powder. Washout 2 (Washout between Periods III and IV) 3- to 7-day washout between Periods III and IV. During Period IV, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period I (placebo run-in), all patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period II, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol 50-μg inhalation powder. Washout 1 (Washout between Periods II and III) 3- to 7-day washout between Periods II and III. During Period III, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. Washout 2 (Washout between Periods III and IV) 3- to 7-day washout between Periods III and IV. During Period IV, patients received a single witnessed dose of montelukast 10-mg oral tablet and salmeterol matching-image placebo inhalation powder. During Period I (placebo run-in), all patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period II, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. Washout 1 (Washout between Periods II and III) 3- to 7-day washout between Periods II and III. During Period III, patients received a single witnessed dose of montelukast 10-mg oral tablet and salmeterol matching-image placebo inhalation powder. Washout 2 (Washout between Periods III and IV) 3- to 7-day washout between Periods III and IV. During Period IV, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol 50-μg inhalation powder. During Period I (placebo run-in), all patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. During Period II, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol matching-image placebo inhalation powder. Washout 1 (Washout between Periods II and III) 3- to 7-day washout between Periods II and III. During Period III, patients received a single witnessed dose of montelukast matching-image placebo oral tablet followed immediately by salmeterol 50-μg inhalation powder. Washout 2 (Washout between Periods III and IV) 3- to 7-day washout between Periods III and IV. During Period IV, patients received a single witnessed dose of montelukast 10-mg oral tablet and salmeterol matching-image placebo inhalation powder.
All Cause Mortality
Montelukast/ Salmeterol/Placebo Montelukast/ Placebo/ Salmeterol Salmeterol / Montelukast/ Placebo Salmeterol/ Placebo/ Montelukast Placebo/ Montelukast/ Salmeterol Placebo/ Salmeterol/ Montelukast
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Montelukast/ Salmeterol/Placebo Montelukast/ Placebo/ Salmeterol Salmeterol / Montelukast/ Placebo Salmeterol/ Placebo/ Montelukast Placebo/ Montelukast/ Salmeterol Placebo/ Salmeterol/ Montelukast
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/7 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%)
Other (Not Including Serious) Adverse Events
Montelukast/ Salmeterol/Placebo Montelukast/ Placebo/ Salmeterol Salmeterol / Montelukast/ Placebo Salmeterol/ Placebo/ Montelukast Placebo/ Montelukast/ Salmeterol Placebo/ Salmeterol/ Montelukast
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/7 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.

Results Point of Contact

Name/Title Senior Vice President, Global Clinical Development
Organization Merck Sharp & Dohme Corp.
Phone 1-800-672-6372
Email ClinicalTrialsDisclosure@merck.com
Responsible Party:
Organon and Co
ClinicalTrials.gov Identifier:
NCT00245570
Other Study ID Numbers:
  • 0476-316
  • MK0476-316
  • 2005_043
First Posted:
Oct 28, 2005
Last Update Posted:
Feb 2, 2022
Last Verified:
Jan 1, 2022