Chronic Asthma
Conditions
Keywords
Chronic asthma
Brief summary
This study will test the safety and effectiveness of a range of doses of MK0476 (montelukast) compared to placebo on improved lung function in patients with chronic asthma.
Interventions
5 Period, Cross-over, Dose-Ranging study. Period I: no treatment. Periods II-V: Single-dose administration of inhaled montelukast (using doses as low as 25 mcg, to as high as 1000 mcg), or montelukast placebo. Two puffs of albuterol or albuterol placebo will be given four hours after montelukast/montelukast placebo.
DRUGComparator: placebo
5 Period, Cross-over, Dose-Ranging study. Period I: no treatment. Periods II-V: Single-dose administration of inhaled montelukast (using doses as low as 25 mcg, to as high as 1000 mcg), or montelukast placebo. Two puffs of albuterol or albuterol placebo will be given four hours after montelukast/montelukast placebo.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
15 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* A person is 15 to 65 years of age. A person has had chronic asthma for at least one year
Exclusion criteria
* A person is a smoker or has smoked more that a pack a day for more than 10 years before stopping * A person has other lung disorders such as COPD (chronic obstructive pulmonary disorder)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FEV1 Over 4 Hours | 0 (=baseline) to 4 hours after treatment with montelukast | FEV1 measurements taken at 0 (=baseline), 10, 20, 30, 45, 60, 120, 180 and 240 minutes contributed to the average change from baseline over 4 hours. The number of minutes between consecutive measurements was used as weighting factor. The time-weighted average change was standardized by dividing by the time associated with the last measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FEV1 Over 90 Minutes After Albuterol/Placebo Administration | 4 hours (equals time point at which albuterol or albuterol placebo is administered) to 5.5 hours after treatment with montelukast | FEV1 measurements taken at 0 (=baseline), 15, 30, 60, and 90 minutes after albuterol/placebo administration contributed to the average change from baseline over 90 minutes. The number of minutes between consecutive measurements was used as weighting factor. The time-weighted average change was standardized by dividing by the time associated with the last measurement. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FEV1 at 8 Hours After Treatment With Montelukast | 0 (baseline) and 8 hours after treatment with montelukast | Average change from baseline in FEV1 at 8 hours after single dose montelukast administration. |
| Change From Baseline in FEV1 at 24 Hours After Treatment With Montelukast | 0 (baseline) and 24 hours after treatment with montelukast | Average change from baseline in FEV1 at 24 hours after single dose montelukast administration. |
Participant flow
Recruitment details
Patients were recruited from 6 centers in the United States between July and December 2008.
Pre-assignment details
117 participants were screened; 49 were excluded. Randomized patients met the following criteria during the prestudy period: FEV1 (Forced expiratory volume in one second) 50-85% predicted while withholding short-acting beta agonist (SABA) and reversibility of airway obstruction \>12% following SABA at Visits 1 and 2.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Combined participants from all arms. | 68 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| First Washout Period of 4-7 Days | Adverse Event | 0 | 0 | 0 | 2 | 0 | 0 | 2 |
| Fourth Intervention(Visit 9 to Visit 10) | Patient unable to attend last visit | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 39.1 years STANDARD_DEVIATION 12.6 |
| FEV1 (Forced Expiratory Volume in One Second) | 2.44 L (Liter) STANDARD_DEVIATION 0.63 |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 67 | 1 / 41 | 0 / 30 | 3 / 66 | 3 / 25 | 0 / 36 |
| serious Total, serious adverse events | 0 / 67 | 0 / 41 | 0 / 30 | 0 / 66 | 0 / 25 | 0 / 36 |
Outcome results
Primary
Change From Baseline in FEV1 Over 4 Hours
FEV1 measurements taken at 0 (=baseline), 10, 20, 30, 45, 60, 120, 180 and 240 minutes contributed to the average change from baseline over 4 hours. The number of minutes between consecutive measurements was used as weighting factor. The time-weighted average change was standardized by dividing by the time associated with the last measurement.
Time frame: 0 (=baseline) to 4 hours after treatment with montelukast
Population: Full analysis set (FAS) population which included all randomized patients who took at least one dose of post randomization study drug (Montelukast or placebo) at either of the intervention visits and had a measurement for analysis available in at least one treatment period of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in FEV1 Over 4 Hours | 0.03 L (Liter) |
| 25 mcg Montelukast | Change From Baseline in FEV1 Over 4 Hours | 0.07 L (Liter) |
| 100 mcg Montelukast | Change From Baseline in FEV1 Over 4 Hours | 0.13 L (Liter) |
| 250 mcg Montelukast | Change From Baseline in FEV1 Over 4 Hours | 0.10 L (Liter) |
| 500 mcg Montelukast | Change From Baseline in FEV1 Over 4 Hours | 0.09 L (Liter) |
| 1000 mcg Montelukast | Change From Baseline in FEV1 Over 4 Hours | 0.12 L (Liter) |
95% CI: [-0.01, 0.08]
95% CI: [0.04, 0.15]
95% CI: [0.02, 0.11]
95% CI: [-0.01, 0.11]
95% CI: [0.04, 0.13]
Secondary
Change From Baseline in FEV1 Over 90 Minutes After Albuterol/Placebo Administration
FEV1 measurements taken at 0 (=baseline), 15, 30, 60, and 90 minutes after albuterol/placebo administration contributed to the average change from baseline over 90 minutes. The number of minutes between consecutive measurements was used as weighting factor. The time-weighted average change was standardized by dividing by the time associated with the last measurement.
Time frame: 4 hours (equals time point at which albuterol or albuterol placebo is administered) to 5.5 hours after treatment with montelukast
Population: Full analysis set (FAS) population which included all randomized patients who took at least one dose of post randomization study drug (albuterol or matching placebo) 4 hours after treatment with montelukast at either of the intervention visits and had a measurement for analysis available in at least one treatment period of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in FEV1 Over 90 Minutes After Albuterol/Placebo Administration | 0.34 L |
| 25 mcg Montelukast | Change From Baseline in FEV1 Over 90 Minutes After Albuterol/Placebo Administration | 0.15 L |
95% CI: [0.04, 0.34]
Other Pre-specified
Change From Baseline in FEV1 at 24 Hours After Treatment With Montelukast
Average change from baseline in FEV1 at 24 hours after single dose montelukast administration.
Time frame: 0 (baseline) and 24 hours after treatment with montelukast
Population: Full analysis set (FAS) population which included all randomized patients who took at least one dose of post randomization study drug (Montelukast or placebo) at either of the intervention visits and had a measurement for analysis available in at least one treatment period of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in FEV1 at 24 Hours After Treatment With Montelukast | 0.02 L |
| 25 mcg Montelukast | Change From Baseline in FEV1 at 24 Hours After Treatment With Montelukast | 0.05 L |
| 100 mcg Montelukast | Change From Baseline in FEV1 at 24 Hours After Treatment With Montelukast | 0.10 L |
| 250 mcg Montelukast | Change From Baseline in FEV1 at 24 Hours After Treatment With Montelukast | 0.06 L |
| 500 mcg Montelukast | Change From Baseline in FEV1 at 24 Hours After Treatment With Montelukast | 0.08 L |
| 1000 mcg Montelukast | Change From Baseline in FEV1 at 24 Hours After Treatment With Montelukast | 0.09 L |
95% CI: [-0.03, 0.1]
95% CI: [0.01, 0.17]
95% CI: [-0.01, 0.1]
95% CI: [-0.02, 0.15]
95% CI: [0.01, 0.15]
Other Pre-specified
Change From Baseline in FEV1 at 8 Hours After Treatment With Montelukast
Average change from baseline in FEV1 at 8 hours after single dose montelukast administration.
Time frame: 0 (baseline) and 8 hours after treatment with montelukast
Population: Full analysis set (FAS) population which included all randomized patients who took at least one dose of post randomization study drug (Montelukast or placebo) at either of the intervention visits and had a measurement for analysis available in at least one treatment period of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in FEV1 at 8 Hours After Treatment With Montelukast | 0.06 L |
| 25 mcg Montelukast | Change From Baseline in FEV1 at 8 Hours After Treatment With Montelukast | 0.11 L |
| 100 mcg Montelukast | Change From Baseline in FEV1 at 8 Hours After Treatment With Montelukast | 0.13 L |
| 250 mcg Montelukast | Change From Baseline in FEV1 at 8 Hours After Treatment With Montelukast | 0.11 L |
| 500 mcg Montelukast | Change From Baseline in FEV1 at 8 Hours After Treatment With Montelukast | 0.12 L |
| 1000 mcg Montelukast | Change From Baseline in FEV1 at 8 Hours After Treatment With Montelukast | 0.14 L |
95% CI: [-0.01, 0.12]
95% CI: [0, 0.15]
95% CI: [-0.01, 0.11]
95% CI: [-0.03, 0.14]
95% CI: [0.01, 0.15]