Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Albuterol HFA MDI in Pediatric Participants With Asthma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00577655
Recruitment Status : Completed
First Posted : December 20, 2007
Results First Posted : December 3, 2009
Last Update Posted : October 25, 2016
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: Albuterol
Drug: Placebo
Drug: Proventil® HFA
Enrollment 103
Recruitment Details  
Pre-assignment Details 208 individual subjects were screened; ten subjects failed the initial screening but were later re-screened and successfully enrolled.
Arm/Group Title Albuterol Placebo
Hide 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 [1] 51 [1]
Completed 51 47
Not Completed 1 4
Reason Not Completed
Patient Request             0             2
Protocol Violation             0             1
Lost to Follow-up             1             1
[1]
This number represents the number of participants randomized.
Arm/Group Title Albuterol Placebo Total
Hide 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 Number of Baseline Participants 52 51 103
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 52 participants 51 participants 103 participants
8.3  (1.82) 8.2  (2.09) 8.2  (1.95)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 51 participants 103 participants
Female
19
  36.5%
20
  39.2%
39
  37.9%
Male
33
  63.5%
31
  60.8%
64
  62.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 52 participants 51 participants 103 participants
White 30 39 69
Black 14 7 21
Asian 5 3 8
North American Indian or Alaska native 1 1 2
Other 2 1 3
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 52 participants 51 participants 103 participants
52 51 103
Forced Expiratory Volume in One Second (FEV1) on Day 1   [1] 
Mean (Standard Deviation)
Unit of measure:  Liters
Number Analyzed 52 participants 51 participants 103 participants
1.52  (0.38) 1.49  (0.46) 1.50  (0.42)
[1]
Measure Description: Baseline measurement is the average of two Day 1 pre-dose FEV1 values. n=51, 51, 103
1.Primary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF)
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 52 51
Mean (Standard Error)
Unit of Measure: percentage change from baseline
12.849  (1.005) 9.353  (1.017)
Show Statistical Analysis 1 Hide 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
Comments [Not Specified]
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
Estimation Comments Active - Placebo
2.Primary Outcome
Title Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) Observed up to Two Hours Post Dose (PEFmax%0-2) on Day 22
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF)
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 52 51
Mean (Standard Error)
Unit of Measure: percentage change from baseline
17.558  (1.878) 12.127  (1.907)
Show Statistical Analysis 1 Hide 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
Comments [Not Specified]
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
Estimation Comments Active - Placebo
3.Secondary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Observed cases (i.e. available data only)
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 51 51
Mean (Standard Error)
Unit of Measure: percentage change from baseline
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)
Show Statistical Analysis 1 Hide 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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0031
Comments significance level of 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.536
Confidence Interval (2-Sided) 95%
1.567 to 7.505
Estimation Comments Active - Placebo
Show Statistical Analysis 2 Hide 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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0470
Comments significance level of 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.067
Confidence Interval (2-Sided) 95%
0.041 to 6.094
Estimation Comments Active - Placebo
4.Secondary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Observed cases
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 52 51
Mean (Standard Error)
Unit of Measure: percentage change from baseline
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)
Show Statistical Analysis 1 Hide 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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0074
Comments significance level of 0.05.
Method repeated measures ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.572
Confidence Interval (2-Sided) 95%
2.077 to 13.067
Estimation Comments Active - Placebo
Show Statistical Analysis 2 Hide 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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1843
Comments significance level of 0.05.
Method repeated measures ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.782
Confidence Interval (2-Sided) 95%
-1.832 to 9.397
Estimation Comments Active - Placebo
5.Secondary Outcome
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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF)
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 52 51
Mean (Standard Error)
Unit of Measure: Percent of Predicted FEV1 * Hours
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 22 Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
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
Estimation Comments Active - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 1 Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
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
Estimation Comments Active - Placebo
6.Secondary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF)
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 52 51
Mean (Standard Error)
Unit of Measure: Liters/Minute*Hours
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 22 Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
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
Estimation Comments Active - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 1 Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
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
Estimation Comments Active - Placebo
7.Secondary Outcome
Title Maximum Percent-Predicted FEV1 (Max PPFEV1, %) Observed up to Two Hours Following Completion of Dosing on Study Days 1 and 22 (Observed Case)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Observed cases (i.e. available data only)
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 51 51
Mean (Standard Error)
Unit of Measure: percentage of predicted FEV1
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
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
Estimation Comments Active - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 22
Type of Statistical Test Superiority or Other
Comments [Not Specified]
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
Estimation Comments Active - Placebo
8.Secondary Outcome
Title Time To Maximum Forced Expiratory Volume in One Second (FEV1) Over Six Hours Post-Dose On Days 1 and 22
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat (ITT) population; Last Observation Carried Forward (LOCF) used for Day 22
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 52 51
Median (95% Confidence Interval)
Unit of Measure: minutes
Day 1 (n=51, 51)
43.95
(32.03 to 51.73)
45.25
(30.32 to 62.82)
Day 22 with LOCF (n=52, 51)
41.54
(29.55 to 45.67)
61.05
(46.53 to 120.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0647
Comments significance level of 0.05.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.477
Confidence Interval (2-Sided) 95%
0.98 to 2.23
Estimation Comments Active/Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 22
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments significance level of 0.05.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 2.088
Confidence Interval (2-Sided) 95%
1.38 to 3.15
Estimation Comments Active/Placebo
9.Secondary Outcome
Title Time To Maximum Peak Expiratory Flow (PEF) Over Six Hours Post-Dose On Days 1 and 22
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; Last Observation Carried Forward (LOCF) used for Day 22
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 52 51
Median (95% Confidence Interval)
Unit of Measure: minutes
Day 1 (n=52, 51)
41.50
(34 to 64)
35.00
(33 to 65)
Day 22 with LOCF (n=52, 51)
34.5
(22 to 50)
63.00
(35 to 115)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5059
Comments significance level of 0.05.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.141
Confidence Interval (2-Sided) 95%
0.77 to 1.69
Estimation Comments Active/Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 22
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0333
Comments significance level of 0.05.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.533
Confidence Interval (2-Sided) 95%
1.03 to 2.27
Estimation Comments Active/Placebo
10.Secondary Outcome
Title Participant Responses: Percentage of Participants With a >=15% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 51 51
Measure Type: Number
Unit of Measure: percentage of participants
Day 1 (n=51, 51) 17.6 9.8
Day 22 (n=51, 47) 17.6 6.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3888
Comments significance level of 0.05.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 22
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1249
Comments significance level of 0.05.
Method Fisher Exact
Comments [Not Specified]
11.Secondary Outcome
Title Participant Responses: Percentage of Participants With a >=12% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 51 51
Measure Type: Number
Unit of Measure: percentage of participants
Day 1 (n=51, 51) 33.3 13.7
Day 22 (n=51, 47) 29.4 14.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0343
Comments significance level of 0.05.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 22
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0962
Comments significance level of 0.05.
Method Fisher Exact
Comments [Not Specified]
12.Secondary Outcome
Title Participant Responses: Percentage of Participants With a >=15% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 52 51
Measure Type: Number
Unit of Measure: percentage of participants
Day 1 (n=52, 51) 44.2 19.6
Day 22 (n=51, 47) 41.2 23.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0109
Comments significance level of 0.05.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 22
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0845
Comments significance level of 0.05.
Method Fisher Exact
Comments [Not Specified]
13.Secondary Outcome
Title Participant Responses: Percentage of Participants With a >=12% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 52 51
Measure Type: Number
Unit of Measure: percentage of participants
Day 1 (n=52, 51) 57.7 25.5
Day 22 (n=51, 47) 56.9 29.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments significance level of 0.05.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Day 22
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0085
Comments significance level of 0.05.
Method Fisher Exact
Comments [Not Specified]
14.Secondary Outcome
Title Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 52 51
Mean (Standard Error)
Unit of Measure: units on a scale
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Week 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
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
Estimation Comments Active - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
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
Estimation Comments Active - Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
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
Estimation Comments Active - Placebo
15.Secondary Outcome
Title The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 52 51
Mean (Standard Deviation)
Unit of Measure: awakenings/week
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)
16.Secondary Outcome
Title Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 52 51
Mean (Standard Error)
Unit of Measure: Liters/minute
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Week 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
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
Estimation Comments Active - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
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
Estimation Comments Active - Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
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
Estimation Comments Active - Placebo
17.Secondary Outcome
Title Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Albuterol Placebo
Hide 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.
Overall Number of Participants Analyzed 52 51
Mean (95% Confidence Interval)
Unit of Measure: Number of puffs per day
Week 1 (N=51, N=50)
0.074
(0.009 to 0.138)
0.075
(0.011 to 0.139)
Week 2 (N=51, N=49)
0.084
(0.011 to 0.158)
0.088
(0.013 to 0.163)
Week 3 (N=49, N=48)
0.078
(0.010 to 0.146)
0.088
(0.013 to 0.163)
Show Statistical Analysis 1 Hide 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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9846
Comments significance level of 0.05.
Method mixed poisson regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of Active to Placebo
Estimated Value 0.989
Confidence Interval (2-Sided) 95%
-0.121 to 2.099
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9447
Comments significance level of 0.05.
Method mixed poisson regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of Active to Placebo
Estimated Value 0.961
Confidence Interval (2-Sided) 95%
-0.116 to 2.039
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide 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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8326
Comments significance level of 0.05.
Method mixed poisson regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of Active to Placebo
Estimated Value 0.887
Confidence Interval (2-Sided) 95%
-0.111 to 1.885
Estimation Comments [Not Specified]
Time Frame Days 1-22
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Albuterol Placebo
Hide 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 (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Albuterol Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/52 (0.00%)      0/51 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Albuterol Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/52 (13.46%)      5/51 (9.80%)    
Infections and infestations     
Nasopharyngitis  1  4/52 (7.69%)  4 0/51 (0.00%)  0
Nervous system disorders     
Headache  1  3/52 (5.77%)  4 5/51 (9.80%)  6
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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 Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT00577655     History of Changes
Other Study ID Numbers: IXR-302-25-105
First Submitted: December 18, 2007
First Posted: December 20, 2007
Results First Submitted: July 21, 2009
Results First Posted: December 3, 2009
Last Update Posted: October 25, 2016