Montelukast Compared With Placebo and Salmeterol in Exercise-Induced Bronchoconstriction - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Crossover Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Prevention
Condition:	Asthma, Exercise-Induced
Interventions:	Drug: Comparator: Montelukast Drug: Comparator: Salmeterol Drug: Comparator: Placebo (montelukast) Drug: Comparator: Placebo (salmeterol)

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were randomized at 5 sites (4 in the US and 1 in Peru). Primary therapy period: December 2005 to August 2006

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients who required excluded medications, or did not meet FEV1 criteria during the prestudy period were excluded from randomization.

Reporting Groups

	Description
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.

Participant Flow for 5 periods

Period 1: Treatment Period II

	Montelukast/ Salmeterol/Placebo	Montelukast/ Placebo/ Salmeterol	Salmeterol / Montelukast/ Placebo	Salmeterol/ Placebo/ Montelukast	Placebo/ Montelukast/ Salmeterol	Placebo/ Salmeterol/ Montelukast
STARTED	7	8	8	8	8	8
COMPLETED	7	8	8	8	8	8
NOT COMPLETED	0	0	0	0	0	0

Period 2: Washout Between Periods II and III

	Montelukast/ Salmeterol/Placebo	Montelukast/ Placebo/ Salmeterol	Salmeterol / Montelukast/ Placebo	Salmeterol/ Placebo/ Montelukast	Placebo/ Montelukast/ Salmeterol	Placebo/ Salmeterol/ Montelukast
STARTED	7	8	8	8	8	8
COMPLETED	7	8	8	8	8	8
NOT COMPLETED	0	0	0	0	0	0

Period 3: Treatment Period III

	Montelukast/ Salmeterol/Placebo	Montelukast/ Placebo/ Salmeterol	Salmeterol / Montelukast/ Placebo	Salmeterol/ Placebo/ Montelukast	Placebo/ Montelukast/ Salmeterol	Placebo/ Salmeterol/ Montelukast
STARTED	7	8	8	8	8	8
COMPLETED	7	8	8	8	8	8
NOT COMPLETED	0	0	0	0	0	0

Period 4: Washout Between Periods III and IV

	Montelukast/ Salmeterol/Placebo	Montelukast/ Placebo/ Salmeterol	Salmeterol / Montelukast/ Placebo	Salmeterol/ Placebo/ Montelukast	Placebo/ Montelukast/ Salmeterol	Placebo/ Salmeterol/ Montelukast
STARTED	7	8 ^[1]	8	8	8	8
COMPLETED	7	7	8	8	8	8
NOT COMPLETED	0	1	0	0	0	0
Adverse Event	0	1	0	0	0	0

[1]	1 pt in the montelukast/placebo/salmeterol group discontinued during washout period 2 after placebo

Period 5: Treatment Period IV

	Montelukast/ Salmeterol/Placebo	Montelukast/ Placebo/ Salmeterol	Salmeterol / Montelukast/ Placebo	Salmeterol/ Placebo/ Montelukast	Placebo/ Montelukast/ Salmeterol	Placebo/ Salmeterol/ Montelukast
STARTED	7	7	8	8	8	8
COMPLETED	7	7	8	8	8	8
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

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Reporting Groups

	Description
Overall Study Population	All randomized patients

Baseline Measures

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

[1]	The duration between the time at which the maximum percent fall in FEV1 occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.

Outcome Measures

Show All Outcome Measures

1. Primary:

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) [ Time Frame: 0-60 minutes after the exercise challenge performed 2 hours after a single oral dose ]

Show Outcome Measure 1

2. Secondary:

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

Show Outcome Measure 2

3. Secondary:

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

Show Outcome Measure 3

4. Secondary:

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

Show Outcome Measure 4

5. Secondary:

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

Show Outcome Measure 5

6. Secondary:

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

Show Outcome Measure 6

7. Secondary:

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 [ Time Frame: 0-60 minutes after the exercise challenge at 2 hours postdose ]

Show Outcome Measure 7

8. Secondary:

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 [ Time Frame: 0-60 minutes after the exercise challenge at 8.5 hours postdose ]

Show Outcome Measure 8

9. Secondary:

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 [ Time Frame: 0-60 minutes after the exercise challenge at 24 hours postdose ]

Show Outcome Measure 9

10. Secondary:

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

Show Outcome Measure 10

11. Secondary:

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

Show Outcome Measure 11

12. Secondary:

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

Show Outcome Measure 12

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Executive Vice President, Clinical and Quantitative Sciences
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372

Publications:

Philip G, Pearlman DS, Villarán C, Legrand C, Loeys T, Langdon RB, Reiss TF. Single-dose montelukast or salmeterol as protection against exercise-induced bronchoconstriction. Chest. 2007 Sep;132(3):875-83. Epub 2007 Jun 15.

Responsible Party:	Executive Vice President, Clinical and Quantitative Sciences, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00245570 History of Changes
Other Study ID Numbers:	2005_043, MK0476-316
Study First Received:	October 26, 2005
Results First Received:	September 25, 2009
Last Updated:	May 27, 2010
Health Authority:	United States: Food and Drug Administration