Asthma
Conditions
Keywords
asthmatic children
Brief summary
The purpose of this study is to examine the safety and efficacy of two doses of MAP0010 versus placebo in asthmatic infants and children, 12 months to 8 years of age, over a 12-week treatment period.
Interventions
DRUG0.135mg MAP0010
0.135mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks
DRUG0.25mg MAP0010
0.25mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks
DRUGPlacebo
Placebo delivered by nebulization twice daily for 12 weeks
Sponsors
MAP Pharmaceuticals, Inc., a wholly owned subsidiary of Allergan
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Months to 8 Years
Healthy volunteers
No
Inclusion criteria
* Male or female asthmatic children with mild to moderate persistent asthma. * 12 months to 8 years of age. * For children age 4 to 8 years: Documented diagnosis of asthma at least 3 months prior to Visit 1, per NIH (EPR-3) criteria. * For infants age 12 to \<48 months old: 2 or more wheezing episodes in past 12 months which lasted \> 1 day and affected sleep. * AND with at least one major or two minor risk factors.
Exclusion criteria
* Any other significant childhood illness/abnormality or chronic lung disease * Any history of upper or lower respiratory tract infection, within 2 weeks of screening. * Any history of acute or severe asthma attack requiring ICU admission or ventilatory support. * Use of any corticosteroid, including inhaled, parental, intranasal, or topical corticosteroid within 2 weeks of screening. * Any use of oral corticosteroids within 30 days of screening or prolonged use (\>10 consecutive days) of oral corticosteroids, within 12 weeks of screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Daytime Composite Symptom Score | baseline, week 12 | The individual symptoms at each time point to be monitored are: cough, wheeze, and shortness of breath. The individual symptoms were scored using a four point scale: 0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms Daily composite symptom score is based on the average of the individual symptom scores for a day. Daytime composite symptom score is defined as average of the last 5 days' daily composite symptom scores within the last 7 days immediately preceding the end day of that week. The range for the daytime composite symptom score is 0 (no symptoms) to 3 (severe symptoms). A negative change indicates an improvement of symptoms and a positive change indicates a worsening of symptoms. |
| Change From Baseline in Nighttime Composite Symptom Score | baseline, week 12 | The individual symptoms at each time point to be monitored are: cough, wheeze, and shortness of breath. The individual symptoms were scored using a four point scale: 0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms Nightly composite symptom score is based on the average of the individual symptom scores for the night. Nightime composite symptom score is defined as average of the last 5 days' nightly composite symptom scores within the last 7 nights immediately preceding the end day of that week. The range for the nighttime composite symptom score is 0 (no symptoms) to 3 (severe symptoms). A negative change indicates an improvement of symptoms and a positive change indicates a worsening of symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FEV1% Predicted | baseline, week 12 | The forced expiratory volume in 1 second (FEV1) is the amount forced of air exhaled in 1 second. The percent predicted is calculated for age, gender, and height. Subjects had to perform at least 3 acceptable maneuvers into a spirometer and the largest volume from the 3 maneuvers was selected. An increase indicates an improvement (a greater volume of air expired). |
| Change From Baseline in PEF | baseline, week 12 | The peak expiratory flow (PEF) is the highest air flow achieved from a maximum forced expiratory maneuver measured in liters of air per minute (L/min). Subjects had to perform at least 3 acceptable maneuvers into a PEF meter. An increase indicates an improvement (a greater volume of air expired). |
| Change From Baseline in Daytime Individual Symptom Scores | baseline, week 12 | The individual symptoms at each time point to be monitored are: cough, wheeze, and shortness of breath. The individual symptoms were scored using a four point scale: 0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms Individual Daytime symptom score is defined as an average of the last 5 days' individual symptom scores within the last 7 days immediately preceding the end day of that week. A negative change indicates an improvement of symptoms and a positive change indicates a worsening of symptoms. |
| Change From Baseline in Nighttime Individual Symptom Scores | baseline, week 12 | The individual symptoms at each time point to be monitored are: cough, wheeze, and shortness of breath. The individual symptoms were scored using a four point scale: 0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms Individual nighttime symptom score is defined as an average of the last 5 nights' individual symptom scores within the last 7 nights immediately preceding the end day of that week. A negative change indicates an improvement of symptoms and a positive change indicates a worsening of symptoms. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo delivered by nebulization twice daily for 12 weeks | 111 |
| 0.135 mg MAP0010 0.135mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks | 125 |
| 0.25 mg MAP0010 0.25mg MAP0010 (unit dose budesonide) delivered by nebulization twice daily for 12 weeks | 124 |
| Total | 360 |
Baseline characteristics
| Characteristic | Placebo | 0.135 mg MAP0010 | 0.25 mg MAP0010 | Total |
|---|---|---|---|---|
| Age, Continuous | 4.0 years | 4.0 years | 4.0 years | 4.0 years |
| Sex: Female, Male Female | 45 Participants | 50 Participants | 49 Participants | 144 Participants |
| Sex: Female, Male Male | 66 Participants | 75 Participants | 75 Participants | 216 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 | 33 / 110 | 31 / 123 | 42 / 123 |
| serious Total, serious adverse events | 1 / 110 | 2 / 123 | 0 / 123 |
Outcome results
Primary
Change From Baseline in Daytime Composite Symptom Score
The individual symptoms at each time point to be monitored are: cough, wheeze, and shortness of breath. The individual symptoms were scored using a four point scale: 0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms Daily composite symptom score is based on the average of the individual symptom scores for a day. Daytime composite symptom score is defined as average of the last 5 days' daily composite symptom scores within the last 7 days immediately preceding the end day of that week. The range for the daytime composite symptom score is 0 (no symptoms) to 3 (severe symptoms). A negative change indicates an improvement of symptoms and a positive change indicates a worsening of symptoms.
Time frame: baseline, week 12
Population: Intent-to-treat includes all randomized patients who have received at least one dose of study drug and have baseline and at least one post treatment efficacy assessment available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Daytime Composite Symptom Score | Baseline | 2.73 units on a scale | Standard Deviation 1.406 |
| Placebo | Change From Baseline in Daytime Composite Symptom Score | Change from Baseline at week 12 | -1.38 units on a scale | Standard Deviation 1.722 |
| 0.135 mg MAP0010 | Change From Baseline in Daytime Composite Symptom Score | Baseline | 2.96 units on a scale | Standard Deviation 1.329 |
| 0.135 mg MAP0010 | Change From Baseline in Daytime Composite Symptom Score | Change from Baseline at week 12 | -1.77 units on a scale | Standard Deviation 1.618 |
| 0.25 mg MAP0010 | Change From Baseline in Daytime Composite Symptom Score | Baseline | 2.87 units on a scale | Standard Deviation 1.383 |
| 0.25 mg MAP0010 | Change From Baseline in Daytime Composite Symptom Score | Change from Baseline at week 12 | -1.56 units on a scale | Standard Deviation 1.591 |
Primary
Change From Baseline in Nighttime Composite Symptom Score
The individual symptoms at each time point to be monitored are: cough, wheeze, and shortness of breath. The individual symptoms were scored using a four point scale: 0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms Nightly composite symptom score is based on the average of the individual symptom scores for the night. Nightime composite symptom score is defined as average of the last 5 days' nightly composite symptom scores within the last 7 nights immediately preceding the end day of that week. The range for the nighttime composite symptom score is 0 (no symptoms) to 3 (severe symptoms). A negative change indicates an improvement of symptoms and a positive change indicates a worsening of symptoms.
Time frame: baseline, week 12
Population: Intent-to-treat includes all randomized patients who have received at least one dose of study drug and have baseline and at least one post treatment efficacy assessment available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Nighttime Composite Symptom Score | Baseline | 2.71 units on a scale | Standard Deviation 1.393 |
| Placebo | Change From Baseline in Nighttime Composite Symptom Score | Change from Baseline at week 12 | -1.47 units on a scale | Standard Deviation 1.572 |
| 0.135 mg MAP0010 | Change From Baseline in Nighttime Composite Symptom Score | Baseline | 2.97 units on a scale | Standard Deviation 1.466 |
| 0.135 mg MAP0010 | Change From Baseline in Nighttime Composite Symptom Score | Change from Baseline at week 12 | -1.82 units on a scale | Standard Deviation 1.907 |
| 0.25 mg MAP0010 | Change From Baseline in Nighttime Composite Symptom Score | Baseline | 2.82 units on a scale | Standard Deviation 1.349 |
| 0.25 mg MAP0010 | Change From Baseline in Nighttime Composite Symptom Score | Change from Baseline at week 12 | -1.59 units on a scale | Standard Deviation 1.516 |
Secondary
Change From Baseline in Daytime Individual Symptom Scores
The individual symptoms at each time point to be monitored are: cough, wheeze, and shortness of breath. The individual symptoms were scored using a four point scale: 0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms Individual Daytime symptom score is defined as an average of the last 5 days' individual symptom scores within the last 7 days immediately preceding the end day of that week. A negative change indicates an improvement of symptoms and a positive change indicates a worsening of symptoms.
Time frame: baseline, week 12
Population: Intent-to-treat includes all randomized patients who have received at least one dose of study drug and have baseline and at least one post treatment efficacy assessment available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Daytime Individual Symptom Scores | Shortness of Breath: Baseline | 0.73 units on a scale | Standard Deviation 0.557 |
| Placebo | Change From Baseline in Daytime Individual Symptom Scores | Wheeze: Baseline | 0.84 units on a scale | Standard Deviation 0.591 |
| Placebo | Change From Baseline in Daytime Individual Symptom Scores | Shortness of Breath: Change from Baseline at Wk 12 | -0.37 units on a scale | Standard Deviation 0.635 |
| Placebo | Change From Baseline in Daytime Individual Symptom Scores | Wheeze: Change from Baseline at week 12 | -0.45 units on a scale | Standard Deviation 0.615 |
| Placebo | Change From Baseline in Daytime Individual Symptom Scores | Cough: Change from Baseline at week 12 | -0.55 units on a scale | Standard Deviation 0.734 |
| Placebo | Change From Baseline in Daytime Individual Symptom Scores | Cough: Baseline | 1.16 units on a scale | Standard Deviation 0.544 |
| 0.135 mg MAP0010 | Change From Baseline in Daytime Individual Symptom Scores | Shortness of Breath: Change from Baseline at Wk 12 | -0.51 units on a scale | Standard Deviation 0.632 |
| 0.135 mg MAP0010 | Change From Baseline in Daytime Individual Symptom Scores | Cough: Baseline | 1.21 units on a scale | Standard Deviation 0.49 |
| 0.135 mg MAP0010 | Change From Baseline in Daytime Individual Symptom Scores | Cough: Change from Baseline at week 12 | -0.68 units on a scale | Standard Deviation 0.705 |
| 0.135 mg MAP0010 | Change From Baseline in Daytime Individual Symptom Scores | Wheeze: Baseline | 0.91 units on a scale | Standard Deviation 0.546 |
| 0.135 mg MAP0010 | Change From Baseline in Daytime Individual Symptom Scores | Wheeze: Change from Baseline at week 12 | -0.58 units on a scale | Standard Deviation 0.563 |
| 0.135 mg MAP0010 | Change From Baseline in Daytime Individual Symptom Scores | Shortness of Breath: Baseline | 0.84 units on a scale | Standard Deviation 0.612 |
| 0.25 mg MAP0010 | Change From Baseline in Daytime Individual Symptom Scores | Wheeze: Change from Baseline at week 12 | -0.49 units on a scale | Standard Deviation 0.589 |
| 0.25 mg MAP0010 | Change From Baseline in Daytime Individual Symptom Scores | Cough: Change from Baseline at week 12 | -0.58 units on a scale | Standard Deviation 0.664 |
| 0.25 mg MAP0010 | Change From Baseline in Daytime Individual Symptom Scores | Shortness of Breath: Change from Baseline at Wk 12 | -0.49 units on a scale | Standard Deviation 0.626 |
| 0.25 mg MAP0010 | Change From Baseline in Daytime Individual Symptom Scores | Shortness of Breath: Baseline | 0.81 units on a scale | Standard Deviation 0.602 |
| 0.25 mg MAP0010 | Change From Baseline in Daytime Individual Symptom Scores | Wheeze: Baseline | 0.88 units on a scale | Standard Deviation 0.55 |
| 0.25 mg MAP0010 | Change From Baseline in Daytime Individual Symptom Scores | Cough: Baseline | 1.18 units on a scale | Standard Deviation 0.582 |
Secondary
Change From Baseline in FEV1% Predicted
The forced expiratory volume in 1 second (FEV1) is the amount forced of air exhaled in 1 second. The percent predicted is calculated for age, gender, and height. Subjects had to perform at least 3 acceptable maneuvers into a spirometer and the largest volume from the 3 maneuvers was selected. An increase indicates an improvement (a greater volume of air expired).
Time frame: baseline, week 12
Population: The modified-intent-to-treat population includes all randomized patients who were deemed capable of spirometry measurements at baseline and at least at one of the post treatment visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in FEV1% Predicted | Baseline | 96.96 percentage of predicted FEV1 | Standard Deviation 18.646 |
| Placebo | Change From Baseline in FEV1% Predicted | Change from Baseline at Week 12 | 1.51 percentage of predicted FEV1 | Standard Deviation 13.068 |
| 0.135 mg MAP0010 | Change From Baseline in FEV1% Predicted | Baseline | 91.20 percentage of predicted FEV1 | Standard Deviation 17.713 |
| 0.135 mg MAP0010 | Change From Baseline in FEV1% Predicted | Change from Baseline at Week 12 | 4.14 percentage of predicted FEV1 | Standard Deviation 12.845 |
| 0.25 mg MAP0010 | Change From Baseline in FEV1% Predicted | Baseline | 93.00 percentage of predicted FEV1 | Standard Deviation 17.305 |
| 0.25 mg MAP0010 | Change From Baseline in FEV1% Predicted | Change from Baseline at Week 12 | 0.36 percentage of predicted FEV1 | Standard Deviation 16.657 |
Secondary
Change From Baseline in Nighttime Individual Symptom Scores
The individual symptoms at each time point to be monitored are: cough, wheeze, and shortness of breath. The individual symptoms were scored using a four point scale: 0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms Individual nighttime symptom score is defined as an average of the last 5 nights' individual symptom scores within the last 7 nights immediately preceding the end day of that week. A negative change indicates an improvement of symptoms and a positive change indicates a worsening of symptoms.
Time frame: baseline, week 12
Population: Intent-to-treat includes all randomized patients who have received at least one dose of study drug and have baseline and at least one post treatment efficacy assessment available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Nighttime Individual Symptom Scores | Cough: Baseline | 1.16 units on a scale | Standard Deviation 0.528 |
| Placebo | Change From Baseline in Nighttime Individual Symptom Scores | Cough: Change from Baseline at week 12 | -0.59 units on a scale | Standard Deviation 0.663 |
| Placebo | Change From Baseline in Nighttime Individual Symptom Scores | Wheeze: Baseline | 0.83 units on a scale | Standard Deviation 0.563 |
| Placebo | Change From Baseline in Nighttime Individual Symptom Scores | Wheeze: Change from Baseline at week 12 | -0.48 units on a scale | Standard Deviation 0.594 |
| Placebo | Change From Baseline in Nighttime Individual Symptom Scores | Shortness of Breath: Baseline | 0.72 units on a scale | Standard Deviation 0.543 |
| Placebo | Change From Baseline in Nighttime Individual Symptom Scores | Shortness of Breath: Change from Baseline at Wk 12 | -0.39 units on a scale | Standard Deviation 0.549 |
| 0.135 mg MAP0010 | Change From Baseline in Nighttime Individual Symptom Scores | Shortness of Breath: Change from Baseline at Wk 12 | -0.56 units on a scale | Standard Deviation 0.69 |
| 0.135 mg MAP0010 | Change From Baseline in Nighttime Individual Symptom Scores | Cough: Baseline | 1.20 units on a scale | Standard Deviation 0.495 |
| 0.135 mg MAP0010 | Change From Baseline in Nighttime Individual Symptom Scores | Wheeze: Change from Baseline at week 12 | -0.57 units on a scale | Standard Deviation 0.704 |
| 0.135 mg MAP0010 | Change From Baseline in Nighttime Individual Symptom Scores | Shortness of Breath: Baseline | 0.83 units on a scale | Standard Deviation 0.622 |
| 0.135 mg MAP0010 | Change From Baseline in Nighttime Individual Symptom Scores | Cough: Change from Baseline at week 12 | -0.69 units on a scale | Standard Deviation 0.72 |
| 0.135 mg MAP0010 | Change From Baseline in Nighttime Individual Symptom Scores | Wheeze: Baseline | 0.94 units on a scale | Standard Deviation 0.592 |
| 0.25 mg MAP0010 | Change From Baseline in Nighttime Individual Symptom Scores | Cough: Change from Baseline at week 12 | -0.61 units on a scale | Standard Deviation 0.638 |
| 0.25 mg MAP0010 | Change From Baseline in Nighttime Individual Symptom Scores | Wheeze: Baseline | 0.90 units on a scale | Standard Deviation 0.548 |
| 0.25 mg MAP0010 | Change From Baseline in Nighttime Individual Symptom Scores | Shortness of Breath: Change from Baseline at Wk 12 | -0.47 units on a scale | Standard Deviation 0.566 |
| 0.25 mg MAP0010 | Change From Baseline in Nighttime Individual Symptom Scores | Wheeze: Change from Baseline at week 12 | -0.51 units on a scale | Standard Deviation 0.603 |
| 0.25 mg MAP0010 | Change From Baseline in Nighttime Individual Symptom Scores | Cough: Baseline | 1.17 units on a scale | Standard Deviation 0.565 |
| 0.25 mg MAP0010 | Change From Baseline in Nighttime Individual Symptom Scores | Shortness of Breath: Baseline | 0.75 units on a scale | Standard Deviation 0.569 |
Secondary
Change From Baseline in PEF
The peak expiratory flow (PEF) is the highest air flow achieved from a maximum forced expiratory maneuver measured in liters of air per minute (L/min). Subjects had to perform at least 3 acceptable maneuvers into a PEF meter. An increase indicates an improvement (a greater volume of air expired).
Time frame: baseline, week 12
Population: The modified-intent-to-treat population includes all randomized patients who were deemed capable of spirometry measurements at baseline and at least at one of the post treatment visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in PEF | Change from Baseline at Week 12 | 0.71 L/min | Standard Deviation 44.544 |
| Placebo | Change From Baseline in PEF | Baseline | 170.94 L/min | Standard Deviation 49.343 |
| 0.135 mg MAP0010 | Change From Baseline in PEF | Baseline | 163.39 L/min | Standard Deviation 52.881 |
| 0.135 mg MAP0010 | Change From Baseline in PEF | Change from Baseline at Week 12 | 20.10 L/min | Standard Deviation 45.444 |
| 0.25 mg MAP0010 | Change From Baseline in PEF | Baseline | 165.34 L/min | Standard Deviation 49.133 |
| 0.25 mg MAP0010 | Change From Baseline in PEF | Change from Baseline at Week 12 | 15.02 L/min | Standard Deviation 45.306 |