Albuterol HFA MDI in Pediatric Participants With Asthma
Sponsor
Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00577655
Collaborator
(none)
103
13
2
11
7.9
0.7
Study Details
Study Description
Brief Summary
The primary objective of this study is to evaluate the chronic-dose and efficacy of Albuterol-HFA-MDI relative to placebo in pediatric asthmatics.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
103 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Phase 3 Study to Evaluate the Chronic-dose Safety and Efficacy of Albuterol-HFA-MDI Relative to Placebo in Pediatric Asthmatics
Study Start Date
:
Aug 1, 2007
Actual Primary Completion Date
:
Jul 1, 2008
Actual Study Completion Date
:
Jul 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Albuterol Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. HFA-MDI refers to a metered-dose inhaler (MDI) utilizing a hydrofluoroalkane (HFA) propellant. |
Drug: Albuterol
Albuterol HFA MDI 180 mcg four times a day (q.i.d) for a total daily albuterol dose of 720 mcg for 21 days.
Other Names:
Drug: Proventil® HFA
Proventil® HFA (albuterol sulfate) Inhalation Aerosol (Key Pharmaceuticals) was used as rescue medication in this study. The rescue medication was over-labeled with instructions for emergency use in which subjects were instructed to self-administer up to two puffs every 20 minutes to a maximum of six puffs for any given episode while attempting to seek medical assistance.
Other Names:
|
| Placebo Comparator: Placebo A placebo of a metered-dose inhaler (MDI) utilizing a hydrofluoroalkane (HFA) propellant. (Hereafter noted as "Placebo-HFA-MDI.") |
Drug: Placebo
Placebo HFA MDI four times a day (q.i.d) for 21 days.
Drug: Proventil® HFA
Proventil® HFA (albuterol sulfate) Inhalation Aerosol (Key Pharmaceuticals) was used as rescue medication in this study. The rescue medication was over-labeled with instructions for emergency use in which subjects were instructed to self-administer up to two puffs every 20 minutes to a maximum of six puffs for any given episode while attempting to seek medical assistance.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Observed up to Two Hours Post Dose (FEV1max%0-2) on Day 22 [35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing on Day 22 or last observation]
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in FEV1 observed up to 2 hours following completion of dosing using Day 22 baseline. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values. The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age.
- Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) Observed up to Two Hours Post Dose (PEFmax%0-2) on Day 22 [30±5 and 5±2 minutes prior to dosing, and at 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing on Day 22 or last observation]
The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in the PEF observed up to 2 hours following completion of dosing using Day 22 baseline. The baseline PEF was defined as the average of the test-day pre-dose baseline PEF values. The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age.
Secondary Outcome Measures
- Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) up to Two Hours Post-Dose (FEV1max%0-2, %) on Study Days 1 and 22 Using Observed Cases [Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing]
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in FEV1 observed up to 2 hours following completion of dosing using test day baseline. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values.
- Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) up to Two Hours Post-Dose (PEFmax%0-2) on Study Days 1 and 22 Using Observed Cases [Days 1 and 22: 30±5 and 5±2 minutes prior to dosing, and 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing]
The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in the PEF observed up to 2 hours following completion of dosing on study days 1 and 22. The baseline PEF was defined as the average of the test-day pre-dose baseline PEF values. The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age.
- Baseline Adjusted Area-under-the-Effect Curve for Percent of Predicted Forced Expiratory Volume in One Second (FEV1) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines [Baseline (Day 1 or Day 22: 35±5 and 10±2 minutes prior to dosing), Day 22 (5±2, 15±5, 30±5, 45±5, 60±10, 120±10, 240±10, and 360±10 minutes post-dosing or last observation)]
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Values are then expressed as the percentage of FE1 values predicted for a 'normal' population. Predicted FEV1 values were computed and adjusted for age, height and gender according to Eigen et al. for subjects 4-5 years of age and to Quanjer et al. for subjects aged 6-11 years using American Thoracic Society (ATS) criteria. The area under-the-effect curves for percent-predicted FEV1 were calculated according to the trapezoidal rule and were based on actual (not scheduled) measurement times.
- Baseline-Adjusted Area-under-the Effect Curve for Peak Expiratory Flow (PEF) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines [Baseline (Day 1 or Day 22: 30±5 and 5±2 minutes prior to dosing Day 22: 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing or last observation]
The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. The area under-the-effect curves for PEF were calculated according to the trapezoidal rule and were based on actual (not scheduled) measurement times.
- Maximum Percent-Predicted FEV1 (Max PPFEV1, %) Observed up to Two Hours Following Completion of Dosing on Study Days 1 and 22 (Observed Case) [Days 1 and 22: 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing]
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Values are then expressed as the percentage of FE1 values predicted for a 'normal' population. Predicted FEV1 values were computed and adjusted for age, height and gender according to Eigen et al. for subjects 4-5 years of age and to Quanjer et al. for subjects aged 6-11 years using American Thoracic Society (ATS) criteria.
- Time To Maximum Forced Expiratory Volume in One Second (FEV1) Over Six Hours Post-Dose On Days 1 and 22 [Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing]
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Time to maximum FEV1 is defined as the number of minutes required for the baseline FEV1 to increase to the highest FEV1 post dose during the 6 hour observation period. Median time and confidence intervals obtained via separate Kaplan-Meier estimates for each study day.
- Time To Maximum Peak Expiratory Flow (PEF) Over Six Hours Post-Dose On Days 1 and 22 [Days 1 and 22: 30±5 and 5±2 minutes prior to dosing, and 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing]
The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. Time to maximum PEF is defined as the number of minutes required for the baseline PEF to increase to the highest PEF post-dose for the 6 hour observation period. Median time and confidence intervals obtained via separate Kaplan-Meier estimates for each study day.
- Participant Responses: Percentage of Participants With a >=15% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 [Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing]
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. This outcome counts participants who responded to therapy by obtaining a >+15% increase in FEV1 within 30 minutes of dose. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values.
- Participant Responses: Percentage of Participants With a >=12% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 [Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing]
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. This outcome counts participants who responded to therapy by obtaining a >+12% increase in FEV1 within 30 minutes of dose. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values.
- Participant Responses: Percentage of Participants With a >=15% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 [Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing]
The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. This outcome counts participants who responded to therapy by obtaining a >+15% increase in PEF within 30 minutes of dose. The baseline PEF was defined as the average of the two test-day pre-dose baseline PEF values.
- Participant Responses: Percentage of Participants With a >=12% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 [Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing]
The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. This outcome counts participants who responded to therapy by obtaining a >+12% increase in PEF within 30 minutes of dose. The baseline PEF was defined as the average of the two test-day pre-dose baseline PEF values.
- Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3 [Weeks 1, 2, 3]
Highest daily asthma symptom scores by study week. For this assessment, patients self-evaluate and record on the diary card the following asthma symptoms experienced during the day (i.e. last 12-14 hours): wheeze, shortness of breath, cough, tightness of chest. The worst of these symptoms were scored daily on a four-point scale: 0 = No symptoms occurred 1 = Symptom occurred but did not interfere with daily activity 2 = Symptom occurred but was sometimes annoying or interfered with daily activity 3 = Symptom present even at rest and was annoying or interfered with daily activity
- The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication [Run-in (Days -21 to -1), Weeks 1, 2, 3]
Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night.
- Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning [Weeks 1, 2, 3]
Participants measured their PEF as trained by taking as deep a breath as possible, placing their mouth firmly around the mouthpiece of the flow meter to form a tight seal, and exhaling as hard and as fast as possible. Subjects repeated the process twice at intervals of approximately 30 seconds, and then recorded the highest of the three PEF values on the diary card.
- Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3 [Weeks 1, 2, 3]
Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night and the number of puffs of rescue albuterol used during the night after going to bed. At the end of each day, the number of puffs of albuterol rescue medication used during the day were recorded.
Eligibility Criteria
Criteria
Ages Eligible for Study:
4 Years
to 11 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- Male and female child aged 4-11 years, inclusive Asthma of a minimum of six months duration that has been stable for at least four weeks prior to screening.
Exclusion Criteria:
- Hospitalization for acute asthma exacerbation greater than two years in 12 months prior to screening and/or received ER treatment or hospitalization for asthma exacerbation.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pediatric Care Medical Group, Inc. | Huntington Beach | California | United States | 92647 |
| 2 | California Allergy & Asthma Medical Group | Palmdale | California | United States | 93551 |
| 3 | Center for Clinical Trials, LLC | Paramount | California | United States | 90723 |
| 4 | Integrated Research Group, Inc | Riverside | California | United States | 92506 |
| 5 | Center for Clinical Trials of Sacramento | Sacramento | California | United States | 95823 |
| 6 | Carlos Piniella, MD | Miami | Florida | United States | 33157 |
| 7 | Sneeze, Wheeze & Itch Associates, Inc. | Normal | Illinois | United States | 61761 |
| 8 | Asthma & Allergy Associates, PC | Elmira | New York | United States | 14901 |
| 9 | ENT & Allergy Associates | Newburgh | New York | United States | 12550 |
| 10 | St. Elizabeth's Children Health Center | Utica | New York | United States | 13502 |
| 11 | Regional Allergy & Asthma Consultants | Asheville | North Carolina | United States | 28801 |
| 12 | Clinical Research Institute of Southern Oregan, PC | Medford | Oregon | United States | 97504 |
| 13 | Virginia Adult & Pediatric Allergy & Asthma | Richmond | Virginia | United States | 23229 |
Sponsors and Collaborators
- Teva Branded Pharmaceutical Products R&D, Inc.
Investigators
- Study Director: Teva Study Physician MD, Teva Branded Pharmaceutical Products R&D, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Teva Branded Pharmaceutical Products R&D, Inc.
ClinicalTrials.gov Identifier:
NCT00577655
Other Study ID Numbers:
- IXR-302-25-105
First Posted:
Dec 20, 2007
Last Update Posted:
Nov 12, 2021
Last Verified:
Nov 1, 2021
Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 208 individual subjects were screened; ten subjects failed the initial screening but were later re-screened and successfully enrolled. |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. |
| Period Title: Overall Study | ||
| STARTED | 52 | 51 |
| COMPLETED | 51 | 47 |
| NOT COMPLETED | 1 | 4 |
Baseline Characteristics
| Arm/Group Title | Albuterol | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. | Total of all reporting groups |
| Overall Participants | 52 | 51 | 103 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
8.3
(1.82)
|
8.2
(2.09)
|
8.2
(1.95)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
19
36.5%
|
20
39.2%
|
39
37.9%
|
| Male |
33
63.5%
|
31
60.8%
|
64
62.1%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| White |
30
57.7%
|
39
76.5%
|
69
67%
|
| Black |
14
26.9%
|
7
13.7%
|
21
20.4%
|
| Asian |
5
9.6%
|
3
5.9%
|
8
7.8%
|
| North American Indian or Alaska native |
1
1.9%
|
1
2%
|
2
1.9%
|
| Other |
2
3.8%
|
1
2%
|
3
2.9%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
52
100%
|
51
100%
|
103
100%
|
| Forced Expiratory Volume in One Second (FEV1) on Day 1 (liters) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [liters] |
1.52
(0.38)
|
1.49
(0.46)
|
1.50
(0.42)
|
Outcome Measures
| Title | Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Observed up to Two Hours Post Dose (FEV1max%0-2) on Day 22 |
|---|---|
| Description | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in FEV1 observed up to 2 hours following completion of dosing using Day 22 baseline. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values. The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age. |
| Time Frame | 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing on Day 22 or last observation |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF) |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo-HFA-MDI four times a day for 21 days. |
| Measure Participants | 52 | 51 |
| Mean (Standard Error) [percentage change from baseline] |
12.849
(1.005)
|
9.353
(1.017)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Efficacy was declared if the test for either primary efficacy endpoint was significant at the 0.025 level. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0138 |
| Comments | In order to control the overall alpha level at the 0.05 value, each of the primary endpoints were tested separately at the 0.025 level of significance. | |
| Method | ANCOVA | |
| Comments | Baseline as covariate and fixed effects of treatment and pooled investigator site. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.496 | |
| Confidence Interval |
(2-Sided) 95% 0.729 to 6.262 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
| Title | Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) Observed up to Two Hours Post Dose (PEFmax%0-2) on Day 22 |
|---|---|
| Description | The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in the PEF observed up to 2 hours following completion of dosing using Day 22 baseline. The baseline PEF was defined as the average of the test-day pre-dose baseline PEF values. The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age. |
| Time Frame | 30±5 and 5±2 minutes prior to dosing, and at 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing on Day 22 or last observation |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF) |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo-HFA-MDI four times a day for 21 days. |
| Measure Participants | 52 | 51 |
| Mean (Standard Error) [percentage change from baseline] |
17.558
(1.878)
|
12.127
(1.907)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Efficacy was declared if the test for either primary efficacy endpoint was significant at the 0.025 level. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0403 |
| Comments | In order to control the overall alpha level at the 0.05 value, each of the primary endpoints were tested separately at the 0.025 level of significance. | |
| Method | ANCOVA | |
| Comments | Baseline as covariate and fixed effects of treatment and pooled investigator site. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 5.431 | |
| Confidence Interval |
(2-Sided) 95% 0.244 to 10.618 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
| Title | Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) up to Two Hours Post-Dose (FEV1max%0-2, %) on Study Days 1 and 22 Using Observed Cases |
|---|---|
| Description | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in FEV1 observed up to 2 hours following completion of dosing using test day baseline. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values. |
| Time Frame | Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| Observed cases (i.e. available data only) |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo-HFA-MDI four times a day for 21 days. |
| Measure Participants | 51 | 51 |
| Day 1 (n=51, 51) |
12.621
(1.072)
|
8.085
(1.075)
|
| Day 22 (n=51, 47) |
12.601
(1.072)
|
9.534
(1.119)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 1 A repeated measures mixed model, with terms for treatment, pooled center, study day, treatment by study day interaction, and baseline as a covariate, and subject as a random term, was used to make comparisons between placebo and active with respect to FEV1max%0-2 at Days 1 and 22, with observed case data. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0031 |
| Comments | significance level of 0.05. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 4.536 | |
| Confidence Interval |
(2-Sided) 95% 1.567 to 7.505 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 22 A repeated measures mixed model, with terms for treatment, pooled center, study day, treatment by study day interaction, and baseline as a covariate, and subject as a random term, was used to make comparisons between placebo and active with respect to FEV1max%0-2 at Days 1 and 22, with observed case data. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0470 |
| Comments | significance level of 0.05. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.067 | |
| Confidence Interval |
(2-Sided) 95% 0.041 to 6.094 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
| Title | Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) up to Two Hours Post-Dose (PEFmax%0-2) on Study Days 1 and 22 Using Observed Cases |
|---|---|
| Description | The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in the PEF observed up to 2 hours following completion of dosing on study days 1 and 22. The baseline PEF was defined as the average of the test-day pre-dose baseline PEF values. The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age. |
| Time Frame | Days 1 and 22: 30±5 and 5±2 minutes prior to dosing, and 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| Observed cases |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo-HFA-MDI four times a day for 21 days. |
| Measure Participants | 52 | 51 |
| Day 1 (n=52, 51) |
20.040
(1.982)
|
12.468
(2.004)
|
| Day 22 (n=51, 47) |
16.776
(1.997)
|
12.994
(2.076)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 1 A repeated measures mixed model, with terms for treatment, pooled center, study day, treatment by study day interaction, and baseline as a covariate, and subject as a random term, was used to make comparisons between placebo and active with respect to PEFmax%0-2 at Days 1 and 22, with observed case data. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0074 |
| Comments | significance level of 0.05. | |
| Method | repeated measures ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 7.572 | |
| Confidence Interval |
(2-Sided) 95% 2.077 to 13.067 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 22 A repeated measures mixed model, with terms for treatment, pooled center, study day, treatment by study day interaction, and baseline as a covariate, and subject as a random term, was used to make comparisons between placebo and active with respect to PEFmax%0-2 at Days 1 and 22, with observed case data. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1843 |
| Comments | significance level of 0.05. | |
| Method | repeated measures ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.782 | |
| Confidence Interval |
(2-Sided) 95% -1.832 to 9.397 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
| Title | Baseline Adjusted Area-under-the-Effect Curve for Percent of Predicted Forced Expiratory Volume in One Second (FEV1) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines |
|---|---|
| Description | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Values are then expressed as the percentage of FE1 values predicted for a 'normal' population. Predicted FEV1 values were computed and adjusted for age, height and gender according to Eigen et al. for subjects 4-5 years of age and to Quanjer et al. for subjects aged 6-11 years using American Thoracic Society (ATS) criteria. The area under-the-effect curves for percent-predicted FEV1 were calculated according to the trapezoidal rule and were based on actual (not scheduled) measurement times. |
| Time Frame | Baseline (Day 1 or Day 22: 35±5 and 10±2 minutes prior to dosing), Day 22 (5±2, 15±5, 30±5, 45±5, 60±10, 120±10, 240±10, and 360±10 minutes post-dosing or last observation) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF) |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. |
| Measure Participants | 52 | 51 |
| Day 22 Baseline (n=52, 51) |
31.046
(3.531)
|
21.338
(3.588)
|
| Day 1 Baseline (n=51, 51) |
25.060
(6.748)
|
24.167
(6.773)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 22 Baseline | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0507 |
| Comments | significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | terms for treatment and center, baseline as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 9.707 | |
| Confidence Interval |
(2-Sided) 95% -0.030 to 19.445 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 1 Baseline | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9240 |
| Comments | significance level of 0.05. | |
| Method | ANOVA | |
| Comments | terms for treatment and center | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.892 | |
| Confidence Interval |
(2-Sided) 95% -17.634 to 19.419 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
| Title | Baseline-Adjusted Area-under-the Effect Curve for Peak Expiratory Flow (PEF) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines |
|---|---|
| Description | The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. The area under-the-effect curves for PEF were calculated according to the trapezoidal rule and were based on actual (not scheduled) measurement times. |
| Time Frame | Baseline (Day 1 or Day 22: 30±5 and 5±2 minutes prior to dosing Day 22: 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing or last observation |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF) |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. |
| Measure Participants | 52 | 51 |
| Day 22 Baseline (n=52, 51) |
120.82
(17.486)
|
90.693
(17.753)
|
| Day 1 Baseline (n=52, 51) |
139.42
(25.782)
|
96.842
(26.117)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 22 Baseline | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2186 |
| Comments | significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | terms for treatment and center, baseline as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 30.124 | |
| Confidence Interval |
(2-Sided) 95% -18.169 to 78.417 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 1 Baseline | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2375 |
| Comments | significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | terms for treatment and center, baseline as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 42.578 | |
| Confidence Interval |
(2-Sided) 95% -28.541 to 113.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
| Title | Maximum Percent-Predicted FEV1 (Max PPFEV1, %) Observed up to Two Hours Following Completion of Dosing on Study Days 1 and 22 (Observed Case) |
|---|---|
| Description | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Values are then expressed as the percentage of FE1 values predicted for a 'normal' population. Predicted FEV1 values were computed and adjusted for age, height and gender according to Eigen et al. for subjects 4-5 years of age and to Quanjer et al. for subjects aged 6-11 years using American Thoracic Society (ATS) criteria. |
| Time Frame | Days 1 and 22: 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| Observed cases (i.e. available data only) |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo-HFA-MDI four times a day for 21 days. |
| Measure Participants | 51 | 51 |
| Day 1 (n=51, 51) |
95.898
(1.451)
|
89.374
(1.462)
|
| Day 22 (n=51, 47) |
94.650
(1.451)
|
90.652
(1.488)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0017 |
| Comments | significance level of 0.05. | |
| Method | ANOVA | |
| Comments | terms for treatment, center, time, time x treatment, subject as a random | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 6.524 | |
| Confidence Interval |
(2-Sided) 95% 2.524 to 10.523 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 22 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0521 |
| Comments | significance level of 0.05. | |
| Method | ANOVA | |
| Comments | terms for treatment, center, time, time x treatment, subject as a random | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.998 | |
| Confidence Interval |
(2-Sided) 95% -0.037 to 8.032 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
| Title | Time To Maximum Forced Expiratory Volume in One Second (FEV1) Over Six Hours Post-Dose On Days 1 and 22 |
|---|---|
| Description | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Time to maximum FEV1 is defined as the number of minutes required for the baseline FEV1 to increase to the highest FEV1 post dose during the 6 hour observation period. Median time and confidence intervals obtained via separate Kaplan-Meier estimates for each study day. |
| Time Frame | Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-To-Treat (ITT) population; Last Observation Carried Forward (LOCF) used for Day 22 |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. |
| Measure Participants | 52 | 51 |
| Day 1 (n=51, 51) |
43.95
|
45.25
|
| Day 22 with LOCF (n=52, 51) |
41.54
|
61.05
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0647 |
| Comments | significance level of 0.05. | |
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.477 | |
| Confidence Interval |
(2-Sided) 95% 0.98 to 2.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active/Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 22 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | significance level of 0.05. | |
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 2.088 | |
| Confidence Interval |
(2-Sided) 95% 1.38 to 3.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active/Placebo | |
| Title | Time To Maximum Peak Expiratory Flow (PEF) Over Six Hours Post-Dose On Days 1 and 22 |
|---|---|
| Description | The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. Time to maximum PEF is defined as the number of minutes required for the baseline PEF to increase to the highest PEF post-dose for the 6 hour observation period. Median time and confidence intervals obtained via separate Kaplan-Meier estimates for each study day. |
| Time Frame | Days 1 and 22: 30±5 and 5±2 minutes prior to dosing, and 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population; Last Observation Carried Forward (LOCF) used for Day 22 |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. |
| Measure Participants | 52 | 51 |
| Day 1 (n=52, 51) |
41.50
|
35.00
|
| Day 22 with LOCF (n=52, 51) |
34.5
|
63.00
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5059 |
| Comments | significance level of 0.05. | |
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.141 | |
| Confidence Interval |
(2-Sided) 95% 0.77 to 1.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active/Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 22 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0333 |
| Comments | significance level of 0.05. | |
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.533 | |
| Confidence Interval |
(2-Sided) 95% 1.03 to 2.27 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active/Placebo | |
| Title | Participant Responses: Percentage of Participants With a >=15% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 |
|---|---|
| Description | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. This outcome counts participants who responded to therapy by obtaining a >+15% increase in FEV1 within 30 minutes of dose. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values. |
| Time Frame | Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. |
| Measure Participants | 51 | 51 |
| Day 1 (n=51, 51) |
17.6
33.8%
|
9.8
19.2%
|
| Day 22 (n=51, 47) |
17.6
33.8%
|
6.4
12.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3888 |
| Comments | significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 22 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1249 |
| Comments | significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Participant Responses: Percentage of Participants With a >=12% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 |
|---|---|
| Description | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. This outcome counts participants who responded to therapy by obtaining a >+12% increase in FEV1 within 30 minutes of dose. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values. |
| Time Frame | Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. |
| Measure Participants | 51 | 51 |
| Day 1 (n=51, 51) |
33.3
64%
|
13.7
26.9%
|
| Day 22 (n=51, 47) |
29.4
56.5%
|
14.9
29.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0343 |
| Comments | significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 22 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0962 |
| Comments | significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Participant Responses: Percentage of Participants With a >=15% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 |
|---|---|
| Description | The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. This outcome counts participants who responded to therapy by obtaining a >+15% increase in PEF within 30 minutes of dose. The baseline PEF was defined as the average of the two test-day pre-dose baseline PEF values. |
| Time Frame | Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. |
| Measure Participants | 52 | 51 |
| Day 1 (n=52, 51) |
44.2
85%
|
19.6
38.4%
|
| Day 22 (n=51, 47) |
41.2
79.2%
|
23.4
45.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0109 |
| Comments | significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 22 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0845 |
| Comments | significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Participant Responses: Percentage of Participants With a >=12% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 |
|---|---|
| Description | The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. This outcome counts participants who responded to therapy by obtaining a >+12% increase in PEF within 30 minutes of dose. The baseline PEF was defined as the average of the two test-day pre-dose baseline PEF values. |
| Time Frame | Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. |
| Measure Participants | 52 | 51 |
| Day 1 (n=52, 51) |
57.7
111%
|
25.5
50%
|
| Day 22 (n=51, 47) |
56.9
109.4%
|
29.8
58.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0013 |
| Comments | significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Day 22 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0085 |
| Comments | significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3 |
|---|---|
| Description | Highest daily asthma symptom scores by study week. For this assessment, patients self-evaluate and record on the diary card the following asthma symptoms experienced during the day (i.e. last 12-14 hours): wheeze, shortness of breath, cough, tightness of chest. The worst of these symptoms were scored daily on a four-point scale: 0 = No symptoms occurred 1 = Symptom occurred but did not interfere with daily activity 2 = Symptom occurred but was sometimes annoying or interfered with daily activity 3 = Symptom present even at rest and was annoying or interfered with daily activity |
| Time Frame | Weeks 1, 2, 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. |
| Measure Participants | 52 | 51 |
| Week 1 (N=50, N=50) |
0.370
(0.070)
|
0.442
(0.070)
|
| Week 2 (N=50, N=49) |
0.376
(0.070)
|
0.547
(0.071)
|
| Week 3 (N=47, N=48) |
0.336
(0.072)
|
0.474
(0.071)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Week 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4674 |
| Comments | significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | terms for treatment, center, week, week by treatment, baseline as a covariate, subject as random. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.072 | |
| Confidence Interval |
(2-Sided) 95% -0.265 to 0.122 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Week 2 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0840 |
| Comments | significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | terms for treatment, center, week, week by treatment, baseline as covariate, subject as random | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.171 | |
| Confidence Interval |
(2-Sided) 95% -0.365 to 0.023 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Week 3 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1699 |
| Comments | significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | terms for treatment, center, week, week by treatment, baseline as covariate, subject as random | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.138 | |
| Confidence Interval |
(2-Sided) 95% -0.335 to 0.059 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
| Title | The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication |
|---|---|
| Description | Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night. |
| Time Frame | Run-in (Days -21 to -1), Weeks 1, 2, 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. |
| Measure Participants | 52 | 51 |
| Run-In (N=52, N=51) |
1.15
(2.97)
|
1.06
(2.44)
|
| Week 1 (N=51, N=50) |
1.14
(3.25)
|
1.00
(2.84)
|
| Week 2 (N=51, N=49) |
1.16
(3.82)
|
0.73
(1.97)
|
| Week 3 (N=49, N=48) |
0.65
(2.21)
|
1.33
(3.13)
|
| Title | Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning |
|---|---|
| Description | Participants measured their PEF as trained by taking as deep a breath as possible, placing their mouth firmly around the mouthpiece of the flow meter to form a tight seal, and exhaling as hard and as fast as possible. Subjects repeated the process twice at intervals of approximately 30 seconds, and then recorded the highest of the three PEF values on the diary card. |
| Time Frame | Weeks 1, 2, 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. |
| Measure Participants | 52 | 51 |
| Week 1 (N=51, N=50) |
229.65
(4.800)
|
219.72
(4.854)
|
| Week 2 (N=51, N=49) |
229.90
(4.800)
|
218.97
(4.870)
|
| Week 3 (N=49, N=48) |
231.28
(4.820)
|
221.73
(4.880)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Week 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1391 |
| Comments | significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | terms for treatment, center, week, week by treatment, baseline as a covariate, subject as random. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 9.926 | |
| Confidence Interval |
(2-Sided) 95% -3.256 to 23.108 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Week 2 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1043 |
| Comments | significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | terms for treatment, center, week, week by treatment, baseline as a covariate, subject as random. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 10.923 | |
| Confidence Interval |
(2-Sided) 95% -2.278 to 24.124 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Week 3 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1570 |
| Comments | significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | terms for treatment, center, week, week by treatment, baseline as a covariate, subject as random. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 9.546 | |
| Confidence Interval |
(2-Sided) 95% -3.705 to 22.798 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Active - Placebo | |
| Title | Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3 |
|---|---|
| Description | Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night and the number of puffs of rescue albuterol used during the night after going to bed. At the end of each day, the number of puffs of albuterol rescue medication used during the day were recorded. |
| Time Frame | Weeks 1, 2, 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Albuterol | Placebo |
|---|---|---|
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | Placebo HFA-MDI four times a day for 21 days. |
| Measure Participants | 52 | 51 |
| Week 1 (N=51, N=50) |
0.074
|
0.075
|
| Week 2 (N=51, N=49) |
0.084
|
0.088
|
| Week 3 (N=49, N=48) |
0.078
|
0.088
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Week 1 P-value, mean and confidence interval calculated from a 0 inflated mixed poisson regression model with fixed effect terms for treatment, week, treatment by week interaction, baseline as a covariate and a random term for subject. The null hypothesis is that the ratio equals 1. Estimated means are conditional upon the random effect, assume a random effect of 0 and a covariate value at the average. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9846 |
| Comments | significance level of 0.05. | |
| Method | mixed poisson regression model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio of Active to Placebo |
| Estimated Value | 0.989 | |
| Confidence Interval |
(2-Sided) 95% -0.121 to 2.099 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Week 2 P-value, mean and confidence interval calculated from a 0 inflated mixed poisson regression model with fixed effect terms for treatment, week, treatment by week interaction, baseline as a covariate and a random term for subject. The null hypothesis is that the ratio equals 1. Estimated means are conditional upon the random effect, assume a random effect of 0 and a covariate value at the average. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9447 |
| Comments | significance level of 0.05. | |
| Method | mixed poisson regression model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio of Active to Placebo |
| Estimated Value | 0.961 | |
| Confidence Interval |
(2-Sided) 95% -0.116 to 2.039 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Albuterol, Placebo |
|---|---|---|
| Comments | Week 3 P-value, mean and confidence interval calculated from a 0 inflated mixed poisson regression model with fixed effect terms for treatment, week, treatment by week interaction, baseline as a covariate and a random term for subject. The null hypothesis is that the ratio equals 1. Estimated means are conditional upon the random effect, assume a random effect of 0 and a covariate value at the average. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8326 |
| Comments | significance level of 0.05. | |
| Method | mixed poisson regression model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio of Active to Placebo |
| Estimated Value | 0.887 | |
| Confidence Interval |
(2-Sided) 95% -0.111 to 1.885 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Days 1-22 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Albuterol | Placebo | ||
| Arm/Group Description | Albuterol-HFA-MDI 180 mcg, four times a day | Placebo HFA-MDI four times a day for 21 days. | ||
All Cause Mortality |
||||
| Albuterol | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Albuterol | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/52 (0%) | 0/51 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Albuterol | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/52 (13.5%) | 5/51 (9.8%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 4/52 (7.7%) | 4 | 0/51 (0%) | 0 |
| Nervous system disorders | ||||
| Headache | 3/52 (5.8%) | 4 | 5/51 (9.8%) | 6 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor has the right 60 days before submission for publication to review/provide comments. If review shows that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for up to 90 additional days to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure of multicenter data, but not longer than 12 months from study completion/termination at all participating sites.
Results Point of Contact
| Name/Title | Teva Study Physician |
|---|---|
| Organization | Teval Global Respiratory Research LLC |
| Phone | 215-293-6482 |
Responsible Party:
Teva Branded Pharmaceutical Products R&D, Inc.
ClinicalTrials.gov Identifier:
NCT00577655
Other Study ID Numbers:
- IXR-302-25-105
First Posted:
Dec 20, 2007
Last Update Posted:
Nov 12, 2021
Last Verified:
Nov 1, 2021