MK0476 Study in Adult Patients With Acute Asthma (0476-322)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00229970
• Collaborator: (none)
• Enrollment: 225
• Arms: 3
• Duration (Months): 21

Study Details

Study Description

Brief Summary

This study evaluates the efficacy and safety of MK0476 intravenous administration in adult patients with acute asthma.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: montelukast sodium; Drug: Comparator: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 225 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: MK0476 Phase II/III Placebo Controlled Double Blind Study
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Oct 1, 2006
• Actual Study Completion Date: Jun 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Placebo	Drug: Comparator: Placebo; Placebo single injection
Experimental: 2 MK0476 7 mg injection	Drug: montelukast sodium; 7 mg or 14 mg single injection
Experimental: 3 MK0476 14 mg injection	Drug: montelukast sodium; 7 mg or 14 mg single injection

Outcome Measures

Primary Outcome Measures

1. The Time-weighted Average of Change in Forced Expiratory Volume in One Second (FEV1) [baseline over the first 60 minutes]

   The Time Weighed Average Changes in Forced Expiratory Volume in One Second (FEV1) from pre-allocation baseline over the first 60 minutes after study drug administration with time interval between any measurement and the measurement prior to it is used as the weighting factor

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult Patients With Acute Asthma Attacks

Exclusion Criteria:

• Patient Has Any Known Or Suspected, Acute Or Chronic Cause For Their Pulmonary Symptoms Other Than Asthma (E.G., Copd, Chronic Heart Failure, Etc.)

• Patient Has A Smoking History (20 Cigarettes Per Day) Of More Than 15 Years

• Patient Has A Disease Of The Cardiovascular, Hepatic, Renal, Hematologic Systems, Or Other Severe Disease

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

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00229970
• Other Study ID Numbers: 0476-322; MK0476-322; 2005_084
• First Posted: Sep 30, 2005
• Last Update Posted: Feb 2, 2022
• Last Verified: Jan 1, 2022

• Additional relevant MeSH terms: Asthma; Montelukast

Study Results

Participant Flow

Recruitment Details	Phase III. Studied period: September 12, 2005 (date study drug was first administered to first patient) to October 23, 2006 (date study drug was last administered to last patient). Study was conducted at 64 clinical sites.
Pre-assignment Detail	Patients with acute exacerbation of bronchial asthma received standard treatments of inhaled β-agonist or oxygen inhalation to treat the acute exacerbations during the 60 minutes in the screening period before the study randomization.

Arm/Group Title	Montelukast 7 mg	Montelukast 14 mg	Placebo
Arm/Group Description	Montelukast 7 mg Intravenous Administration	Montelukast 14 mg Intravenous Administration	Placebo Intravenous Administration
Period Title: Overall Study
STARTED	78	72	75
COMPLETED	78	72	75
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Montelukast 7 mg	Montelukast 14 mg	Placebo	Total
Arm/Group Description	Montelukast 7 mg Intravenous Administration	Montelukast 14 mg Intravenous Administration	Placebo Intravenous Administration	Total of all reporting groups
Overall Participants	78	72	75	225
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.5 (12.5)	41.5 (13.1)	42.3 (12.5)	41.4 (12.7)
Sex: Female, Male (Count of Participants)
Female	41 52.6%	34 47.2%	36 48%	111 49.3%
Male	37 47.4%	38 52.8%	39 52%	114 50.7%
Asthma Attack Severity based on Asthma Prevention and Management Guideline 2003, Japan (participants) [Number]
Mild	54 69.2%	44 61.1%	56 74.7%	154 68.4%
Moderate	23 29.5%	28 38.9%	19 25.3%	70 31.1%
Severe	1 1.3%	0 0%	0 0%	1 0.4%
Serious	0 0%	0 0%	0 0%	0 0%
Baseline Forced Expiratory Volume in One Second (FEV1) (Liter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Liter]	1.67 (0.55)	1.62 (0.59)	1.76 (0.61)	1.68 (0.58)
Duration of Asthma (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	18.7 (11.5)	15.46 (11.6)	17.7 (11.7)	17.3 (11.6)

Outcome Measures

1. Primary Outcome

Title	The Time-weighted Average of Change in Forced Expiratory Volume in One Second (FEV1)
Description	The Time Weighed Average Changes in Forced Expiratory Volume in One Second (FEV1) from pre-allocation baseline over the first 60 minutes after study drug administration with time interval between any measurement and the measurement prior to it is used as the weighting factor
Time Frame	baseline over the first 60 minutes

Outcome Measure Data

Analysis Population Description

Last observed value during the 60 minutes treatment period was used in the Full Analysis Set (FAS)

Arm/Group Title	Montelukast 7 mg	Montelukast 14 mg	Placebo
Arm/Group Description	Montelukast 7 mg Intravenous Administration	Montelukast 14 mg Intravenous Administration	Placebo Intravenous Administration
Measure Participants	78	72	75
Least Squares Mean (95% Confidence Interval) [Liter]	0.09	0.17	0.01

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Montelukast 7 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	ANCOVA
	Comments	The model included a factor for treatment and using the baseline Forced Expiratory Volume in One Second (FEV1) as a covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.09
	Confidence Interval	() 95%; 0.01 to 0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Montelukast 14 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	The model included a factor for treatment and using the baseline Forced Expiratory Volume in One Second (FEV1) as a covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.17
	Confidence Interval	() 95%; 0.09 to 0.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Montelukast 7 mg		Montelukast 14 mg		Placebo
Arm/Group Description	Montelukast 7 mg Intravenous Administration		Montelukast 14 mg Intravenous Administration		Placebo Intravenous Administration
All Cause Mortality
	Montelukast 7 mg		Montelukast 14 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Montelukast 7 mg		Montelukast 14 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/ (NaN)		4/ (NaN)		4/ (NaN)
Gastrointestinal disorders
Abdominal pain	0/78 (0%)		0/72 (0%)		1/75 (1.3%)
Gastritis	1/78 (1.3%)		0/72 (0%)		0/75 (0%)
Infections and infestations
Acute tonsillitis	0/78 (0%)		0/72 (0%)		1/75 (1.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/78 (1.3%)		4/72 (5.6%)		2/75 (2.7%)
Other (Not Including Serious) Adverse Events
	Montelukast 7 mg		Montelukast 14 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/ (NaN)		11/ (NaN)		13/ (NaN)
General disorders
Chest pain	0/78 (0%)		0/72 (0%)		2/75 (2.7%)
Infections and infestations
Bronchitis acute	0/78 (0%)		2/72 (2.8%)		0/75 (0%)
Nasopharyngitis	5/78 (6.4%)		2/72 (2.8%)		5/75 (6.7%)
Investigations
Blood bilirubin increased	2/77 (2.6%)		0/72 (0%)		0/75 (0%)
Blood potassium decreased	2/76 (2.6%)		0/72 (0%)		1/73 (1.4%)
Blood urine present	1/75 (1.3%)		2/70 (2.9%)		1/75 (1.3%)
Glucose urine present	4/75 (5.3%)		0/70 (0%)		1/75 (1.3%)
Protein urine present	2/75 (2.7%)		0/70 (0%)		1/75 (1.3%)
White blood cell count increased	4/77 (5.2%)		4/70 (5.7%)		2/75 (2.7%)
Nervous system disorders
Headache	1/78 (1.3%)		0/72 (0%)		2/75 (2.7%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	4/78 (5.1%)		1/72 (1.4%)		0/75 (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.