Trial Outcomes & Findings for Montelukast Compared With Placebo and Salmeterol in Exercise-Induced Bronchoconstriction (0476-316) (NCT NCT00245570)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

47 participants

Primary outcome timeframe

0-60 minutes after the exercise challenge performed 2 hours after a single oral dose

Results posted on

2022-02-02

Participant Flow

Patients were randomized at 5 sites (4 in the US and 1 in Peru). Primary therapy period: December 2005 to August 2006

Patients who required excluded medications, or did not meet FEV1 criteria during the prestudy period were excluded from randomization.

Participant milestones

Participant milestones
Measure	Montelukast/ Salmeterol/Placebo 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.	Montelukast/ Placebo/ Salmeterol 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.	Salmeterol / Montelukast/ Placebo 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.	Salmeterol/ Placebo/ Montelukast 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.	Placebo/ Montelukast/ Salmeterol 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.	Placebo/ Salmeterol/ Montelukast 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.
Treatment Period II STARTED	7	8	8	8	8	8
Treatment Period II COMPLETED	7	8	8	8	8	8
Treatment Period II NOT COMPLETED	0	0	0	0	0	0
Washout Between Periods II and III STARTED	7	8	8	8	8	8
Washout Between Periods II and III COMPLETED	7	8	8	8	8	8
Washout Between Periods II and III NOT COMPLETED	0	0	0	0	0	0
Treatment Period III STARTED	7	8	8	8	8	8
Treatment Period III COMPLETED	7	8	8	8	8	8
Treatment Period III NOT COMPLETED	0	0	0	0	0	0
Washout Between Periods III and IV STARTED	7	8	8	8	8	8
Washout Between Periods III and IV COMPLETED	7	7	8	8	8	8
Washout Between Periods III and IV NOT COMPLETED	0	1	0	0	0	0
Treatment Period IV STARTED	7	7	8	8	8	8
Treatment Period IV COMPLETED	7	7	8	8	8	8
Treatment Period IV NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Montelukast/ Salmeterol/Placebo 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.	Montelukast/ Placebo/ Salmeterol 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.	Salmeterol / Montelukast/ Placebo 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.	Salmeterol/ Placebo/ Montelukast 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.	Placebo/ Montelukast/ Salmeterol 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.	Placebo/ Salmeterol/ Montelukast 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.
Washout Between Periods III and IV Adverse Event	0	1	0	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study Population n=47 Participants All randomized patients
Age, Continuous	26.0 years STANDARD_DEVIATION 7.92 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants
Need for β-agonist rescue medication following exercise challenge No	31 participants n=5 Participants
Need for β-agonist rescue medication following exercise challenge Yes	16 participants n=5 Participants
Area under the FEV1 percent change from baseline time curve for 0-60 mins after exercise challenge	957.46 % * minutes STANDARD_DEVIATION 518.69 • n=5 Participants
Maximum percent fall in forced expiratory volume in 1 second (FEV1) post-exercise challenge	27.75 Percent Change from Baseline STANDARD_DEVIATION 6.26 • n=5 Participants
Time to recovery from maximal percent fall	55.03 Minutes STANDARD_DEVIATION 32.62 • n=5 Participants

PRIMARY outcome

Timeframe: 0-60 minutes after the exercise challenge performed 2 hours after a single oral dose

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Montelukast 10 mg n=47 Participants All Montelukast 10 mg patients from all Treatment Periods.	Salmeterol 50-μg n=46 Participants All Salmeterol 50-μg patients from all Treatment Periods.	Placebo n=47 Participants All Placebo patients from all Treatment Periods.
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)	13.15 Percent Change from Baseline Standard Deviation 10.28	10.46 Percent Change from Baseline Standard Deviation 9.95	21.86 Percent Change from Baseline Standard Deviation 13.44

SECONDARY outcome

Timeframe: 0-90 minutes after the exercise challenge performed at 2 hours postdose

Population: 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.

Outcome measures

Outcome measures
Measure	Montelukast 10 mg n=47 Participants All Montelukast 10 mg patients from all Treatment Periods.	Salmeterol 50-μg n=46 Participants All Salmeterol 50-μg patients from all Treatment Periods.	Placebo n=47 Participants All Placebo patients from all Treatment Periods.
Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose Patients Requiring Rescue Medication	3 Participants	4 Participants	9 Participants
Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose Patients Not Requiring Rescue Medication	44 Participants	42 Participants	38 Participants

SECONDARY outcome

Timeframe: 0-90 minutes after the exercise challenge performed at 8.5 hours postdose

Population: 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.

Outcome measures

Outcome measures
Measure	Montelukast 10 mg n=40 Participants All Montelukast 10 mg patients from all Treatment Periods.	Salmeterol 50-μg n=39 Participants All Salmeterol 50-μg patients from all Treatment Periods.	Placebo n=37 Participants All Placebo patients from all Treatment Periods.
Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 8.5 Hours Postdose Patients Requiring Rescue Medication	0 Participants	0 Participants	4 Participants
Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 8.5 Hours Postdose Patients Not Requiring Rescue Medication	40 Participants	39 Participants	33 Participants

SECONDARY outcome

Timeframe: 0-90 minutes after the exercise challenge performed at 24 hours postdose

Population: 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.

Outcome measures

Outcome measures
Measure	Montelukast 10 mg n=46 Participants All Montelukast 10 mg patients from all Treatment Periods.	Salmeterol 50-μg n=46 Participants All Salmeterol 50-μg patients from all Treatment Periods.	Placebo n=46 Participants All Placebo patients from all Treatment Periods.
Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose Patients Requiring Rescue Medication	3 Participants	6 Participants	6 Participants
Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose Patients Not Requiring Rescue Medication	43 Participants	40 Participants	40 Participants

SECONDARY outcome

Timeframe: 0-60 minutes after the exercise challenge performed 8.5 hours after a single oral dose

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Montelukast 10 mg n=40 Participants All Montelukast 10 mg patients from all Treatment Periods.	Salmeterol 50-μg n=39 Participants All Salmeterol 50-μg patients from all Treatment Periods.	Placebo n=37 Participants All Placebo patients from all Treatment Periods.
Maximum Percent Fall in FEV1 After Exercise Challenge at 8.5 Hours Post-dose in Patients With EIB	11.60 Percent Change from Baseline Standard Deviation 9.64	11.01 Percent Change from Baseline Standard Deviation 7.56	16.65 Percent Change from Baseline Standard Deviation 12.76

SECONDARY outcome

Timeframe: 0-60 minutes after the exercise challenge performed 24 hours after a single oral dose

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Montelukast 10 mg n=46 Participants All Montelukast 10 mg patients from all Treatment Periods.	Salmeterol 50-μg n=46 Participants All Salmeterol 50-μg patients from all Treatment Periods.	Placebo n=46 Participants All Placebo patients from all Treatment Periods.
Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Post-dose in Patients With EIB	10.09 Percent Change from Baseline Standard Deviation 11.10	16.22 Percent Change from Baseline Standard Deviation 13.09	13.64 Percent Change from Baseline Standard Deviation 9.67

SECONDARY outcome

Timeframe: 0-60 minutes after the exercise challenge at 2 hours postdose

Population: 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.

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

Outcome measures

Outcome measures
Measure	Montelukast 10 mg n=47 Participants All Montelukast 10 mg patients from all Treatment Periods.	Salmeterol 50-μg n=46 Participants All Salmeterol 50-μg patients from all Treatment Periods.	Placebo n=47 Participants All Placebo patients from all Treatment Periods.
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	254.60 Percent * minutes Standard Deviation 241.17	293.05 Percent * minutes Standard Deviation 362.33	710.43 Percent * minutes Standard Deviation 529.91

SECONDARY outcome

Timeframe: 0-60 minutes after the exercise challenge at 8.5 hours postdose

Population: 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.

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

Outcome measures

Outcome measures
Measure	Montelukast 10 mg n=40 Participants All Montelukast 10 mg patients from all Treatment Periods.	Salmeterol 50-μg n=39 Participants All Salmeterol 50-μg patients from all Treatment Periods.	Placebo n=37 Participants All Placebo patients from all Treatment Periods.
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	191.01 Percent * minutes Standard Deviation 166.24	276.26 Percent * minutes Standard Deviation 226.37	511.28 Percent * minutes Standard Deviation 566.30

SECONDARY outcome

Timeframe: 0-60 minutes after the exercise challenge at 24 hours postdose

Population: 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.

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

Outcome measures

Outcome measures
Measure	Montelukast 10 mg n=46 Participants All Montelukast 10 mg patients from all Treatment Periods.	Salmeterol 50-μg n=46 Participants All Salmeterol 50-μg patients from all Treatment Periods.	Placebo n=46 Participants All Placebo patients from all Treatment Periods.
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	231.09 Percent * minutes Standard Deviation 413.73	554.93 Percent * minutes Standard Deviation 649.52	395.96 Percent * minutes Standard Deviation 464.92

SECONDARY outcome

Timeframe: Exercise challenge at 2 hours postdose

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Montelukast 10 mg n=47 Participants All Montelukast 10 mg patients from all Treatment Periods.	Salmeterol 50-μg n=46 Participants All Salmeterol 50-μg patients from all Treatment Periods.	Placebo n=47 Participants All Placebo patients from all Treatment Periods.
Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 2 Hours Postdose	16.63 Minutes Standard Deviation 23.72	17.58 Minutes Standard Deviation 27.81	42.70 Minutes Standard Deviation 34.26

SECONDARY outcome

Timeframe: Exercise challenge at 8.5 hours postdose

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Montelukast 10 mg n=40 Participants All Montelukast 10 mg patients from all Treatment Periods.	Salmeterol 50-μg n=39 Participants All Salmeterol 50-μg patients from all Treatment Periods.	Placebo n=37 Participants All Placebo patients from all Treatment Periods.
Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 8.5 Hours Postdose	10.70 Minutes Standard Deviation 13.38	13.82 Minutes Standard Deviation 18.37	32.34 Minutes Standard Deviation 34.57

SECONDARY outcome

Timeframe: Exercise challenge at 24 hours postdose

Population: 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.

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.