Asthma
Conditions
Brief summary
The study estimates the efficacy and safety of MK0476 and aminophylline intravenous administration in adult participants with acute asthma.
Interventions
DRUGmontelukast sodium
Montelukast 7 mg single injection (IV bolus administration) over 2-3 minutes
DRUGaminophylline hydrate
Aminophylline 250 mg IV drip infusion over 60 minutes
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adult participants with acute asthma attacks
Exclusion criteria
* Participant has any known or suspected, acute or chronic cause for their pulmonary symptoms other than asthma (e.g., COPD, chronic heart failure, etc.). * Participant has a smoking habit (15 cigarettes per day) within a month prior to screening period, and/or has a smoking history (20 cigarettes per day) of more than 15 years. * Participant has a disease of the cardiovascular, hepatic, renal, hematologic systems, or other severe disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Within the First 60 Minutes After Administration | Baseline and 60 minutes after study drug administration | The time weighted average change from Baseline in Forced Expiratory Volume in One Second (FEV1) over the first 60 minutes after study drug administration (average change FEV1 (0-60 min)). Baseline (pre-allocation) was the last measurement obtained during the screening period. |
Participant flow
Recruitment details
Phase III. Studied period: March 12, 2007 (date study drug was first administered to first participant) to August 1, 2007 (date study drug was last administered to last participant). Study was conducted at 31 clinical sites.
Pre-assignment details
Participants 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.
Participants by arm
| Arm | Count |
|---|---|
| Montelukast 7 mg Montelukast 7 mg IV Administration | 30 |
| Montelukast 14 mg Montelukast 14 mg Intravenous Administration | 30 |
| Aminophylline 250 mg Aminophylline 250 mg IV drip administration | 31 |
| Total | 91 |
Baseline characteristics
| Characteristic | Montelukast 7 mg | Montelukast 14 mg | Aminophylline 250 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 56.0 Years STANDARD_DEVIATION 12.3 | 56.7 Years STANDARD_DEVIATION 15.2 | 55.4 Years STANDARD_DEVIATION 14.5 | 56.0 Years STANDARD_DEVIATION 13.9 |
| Age, Customized Adolescents (12-17 years) | 0 Participants 12.3 | 1 Participants 15.2 | 0 Participants 14.5 | 1 Participants |
| Age, Customized Adults (18-64 years) | 21 Participants | 16 Participants | 20 Participants | 57 Participants |
| Age, Customized From 65-84 years | 9 Participants | 13 Participants | 11 Participants | 33 Participants |
| Asthma Attack Severity based on Asthma Prevention and Management Guideline 2003, Japan Mild | 21 Participants 0.29 | 18 Participants 0.33 | 26 Participants 0.53 | 65 Participants |
| Asthma Attack Severity based on Asthma Prevention and Management Guideline 2003, Japan Moderate | 9 Participants | 12 Participants | 5 Participants | 26 Participants |
| Asthma Attack Severity based on Asthma Prevention and Management Guideline 2003, Japan Serious | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Asthma Attack Severity based on Asthma Prevention and Management Guideline 2003, Japan Severe | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Baseline Forced Expiratory Volume in One Second (FEV1) | 1.35 Liter STANDARD_DEVIATION 0.29 | 1.18 Liter STANDARD_DEVIATION 0.33 | 1.43 Liter STANDARD_DEVIATION 0.53 | 1.32 Liter STANDARD_DEVIATION 0.41 |
| Duration of Asthma | 14.9 Years STANDARD_DEVIATION 10.4 | 13.9 Years STANDARD_DEVIATION 11.5 | 16.7 Years STANDARD_DEVIATION 14.1 | 15.2 Years STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 22 Participants | 24 Participants | 16 Participants | 62 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 15 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 30 | 1 / 30 | 3 / 31 |
| serious Total, serious adverse events | 3 / 30 | 0 / 30 | 1 / 31 |
Outcome results
Primary
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Within the First 60 Minutes After Administration
The time weighted average change from Baseline in Forced Expiratory Volume in One Second (FEV1) over the first 60 minutes after study drug administration (average change FEV1 (0-60 min)). Baseline (pre-allocation) was the last measurement obtained during the screening period.
Time frame: Baseline and 60 minutes after study drug administration
Population: Per Protocol Set (PPS): subset of participants who comply with the protocol sufficiently to ensure that these data will likely exhibit effects of treatment, according to the underlying scientific model. Aminophylline 250 mg - 1 participant with no FEV1 data at 60 minutes was excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast 7 mg | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Within the First 60 Minutes After Administration | 0.07 Liter |
| Montelukast 14 mg | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Within the First 60 Minutes After Administration | 0.05 Liter |
| Aminophylline 250 mg | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Within the First 60 Minutes After Administration | 0.06 Liter |
Comparison: Treatment difference in change from Baseline in FEV1 within the first 60 minutes after study drug administration was assessed as the difference in the least square (LS) means of time weighted average change FEV1 (0-60 min) using an Analysis of Covariance (ANCOVA) model.p-value: 0.87195% CI: [-0.07, 0.08]ANCOVA
Comparison: Treatment difference in change from Baseline in FEV1 within the first 60 minutes after study drug administration was assessed as the difference in the LS means of time weighted average change FEV1 (0-60 min) using an ANCOVA model.p-value: 0.79495% CI: [-0.08, 0.06]ANCOVA
Comparison: Treatment difference in change from Baseline in FEV1 within the first 60 minutes after study drug administration was assessed as the difference in the LS means of time weighted average change FEV1 (0-60 min) using an ANCOVA model.p-value: 0.67595% CI: [-0.06, 0.09]ANCOVA