Trial Outcomes & Findings for Albuterol HFA MDI in Pediatric Participants With Asthma (NCT NCT00577655)

NCT ID: NCT00577655

Last Updated: 2021-11-12

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 103 participants
• Primary outcome timeframe: 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
• Results posted on: 2021-11-12

Participant Flow

208 individual subjects were screened; ten subjects failed the initial screening but were later re-screened and successfully enrolled.

Participant milestones

Measure	Albuterol Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo Placebo HFA-MDI four times a day for 21 days.
Overall Study STARTED	52	51
Overall Study COMPLETED	51	47
Overall Study NOT COMPLETED	1	4

Reasons for withdrawal

Measure	Albuterol Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo Placebo HFA-MDI four times a day for 21 days.
Overall Study Patient Request	0	2
Overall Study Protocol Violation	0	1
Overall Study Lost to Follow-up	1	1

Baseline Characteristics

Albuterol HFA MDI in Pediatric Participants With Asthma

Baseline characteristics by cohort

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo HFA-MDI four times a day for 21 days.	Total n=103 Participants Total of all reporting groups
Age, Continuous	8.3 Years STANDARD_DEVIATION 1.82 • n=5 Participants	8.2 Years STANDARD_DEVIATION 2.09 • n=7 Participants	8.2 Years STANDARD_DEVIATION 1.95 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	20 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	31 Participants n=7 Participants	64 Participants n=5 Participants
Race/Ethnicity, Customized White	30 participants n=5 Participants	39 participants n=7 Participants	69 participants n=5 Participants
Race/Ethnicity, Customized Black	14 participants n=5 Participants	7 participants n=7 Participants	21 participants n=5 Participants
Race/Ethnicity, Customized Asian	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Race/Ethnicity, Customized North American Indian or Alaska native	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United States	52 participants n=5 Participants	51 participants n=7 Participants	103 participants n=5 Participants
Forced Expiratory Volume in One Second (FEV1) on Day 1	1.52 liters STANDARD_DEVIATION 0.38 • n=5 Participants	1.49 liters STANDARD_DEVIATION 0.46 • n=7 Participants	1.50 liters STANDARD_DEVIATION 0.42 • n=5 Participants

PRIMARY outcome

Timeframe: 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

Population: Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF)

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.

Outcome measures

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
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	12.849 percentage change from baseline Standard Error 1.005	9.353 percentage change from baseline Standard Error 1.017

PRIMARY outcome

Timeframe: 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

Population: Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF)

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.

Outcome measures

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) Observed up to Two Hours Post Dose (PEFmax%0-2) on Day 22	17.558 percentage change from baseline Standard Error 1.878	12.127 percentage change from baseline Standard Error 1.907

SECONDARY outcome

Timeframe: 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

Population: Observed cases (i.e. available data only)

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.

Outcome measures

Measure	Albuterol n=51 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
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 Day 1 (n=51, 51)	12.621 percentage change from baseline Standard Error 1.072	8.085 percentage change from baseline Standard Error 1.075
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 Day 22 (n=51, 47)	12.601 percentage change from baseline Standard Error 1.072	9.534 percentage change from baseline Standard Error 1.119

SECONDARY outcome

Timeframe: 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

Population: Observed cases

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.

Outcome measures

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
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 Day 1 (n=52, 51)	20.040 percentage change from baseline Standard Error 1.982	12.468 percentage change from baseline Standard Error 2.004
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 Day 22 (n=51, 47)	16.776 percentage change from baseline Standard Error 1.997	12.994 percentage change from baseline Standard Error 2.076

SECONDARY outcome

Timeframe: 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)

Population: Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF)

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.

Outcome measures

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
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 Day 22 Baseline (n=52, 51)	31.046 Percent of Predicted FEV1 * Hours Standard Error 3.531	21.338 Percent of Predicted FEV1 * Hours Standard Error 3.588
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 Day 1 Baseline (n=51, 51)	25.060 Percent of Predicted FEV1 * Hours Standard Error 6.748	24.167 Percent of Predicted FEV1 * Hours Standard Error 6.773

SECONDARY outcome

Timeframe: 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

Population: Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF)

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.

Outcome measures

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
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 Day 22 Baseline (n=52, 51)	120.82 Liters/Minute*Hours Standard Error 17.486	90.693 Liters/Minute*Hours Standard Error 17.753
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 Day 1 Baseline (n=52, 51)	139.42 Liters/Minute*Hours Standard Error 25.782	96.842 Liters/Minute*Hours Standard Error 26.117

SECONDARY outcome

Timeframe: Days 1 and 22: 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing

Population: Observed cases (i.e. available data only)

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.

Outcome measures

Measure	Albuterol n=51 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
Maximum Percent-Predicted FEV1 (Max PPFEV1, %) Observed up to Two Hours Following Completion of Dosing on Study Days 1 and 22 (Observed Case) Day 1 (n=51, 51)	95.898 percentage of predicted FEV1 Standard Error 1.451	89.374 percentage of predicted FEV1 Standard Error 1.462
Maximum Percent-Predicted FEV1 (Max PPFEV1, %) Observed up to Two Hours Following Completion of Dosing on Study Days 1 and 22 (Observed Case) Day 22 (n=51, 47)	94.650 percentage of predicted FEV1 Standard Error 1.451	90.652 percentage of predicted FEV1 Standard Error 1.488

SECONDARY outcome

Timeframe: 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

Population: Intent-To-Treat (ITT) population; Last Observation Carried Forward (LOCF) used for Day 22

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.

Outcome measures

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
Time To Maximum Forced Expiratory Volume in One Second (FEV1) Over Six Hours Post-Dose On Days 1 and 22 Day 1 (n=51, 51)	43.95 minutes Interval 32.03 to 51.73	45.25 minutes Interval 30.32 to 62.82
Time To Maximum Forced Expiratory Volume in One Second (FEV1) Over Six Hours Post-Dose On Days 1 and 22 Day 22 with LOCF (n=52, 51)	41.54 minutes Interval 29.55 to 45.67	61.05 minutes Interval 46.53 to 120.7

SECONDARY outcome

Timeframe: 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

Population: ITT population; Last Observation Carried Forward (LOCF) used for Day 22

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.

Outcome measures

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
Time To Maximum Peak Expiratory Flow (PEF) Over Six Hours Post-Dose On Days 1 and 22 Day 1 (n=52, 51)	41.50 minutes Interval 34.0 to 64.0	35.00 minutes Interval 33.0 to 65.0
Time To Maximum Peak Expiratory Flow (PEF) Over Six Hours Post-Dose On Days 1 and 22 Day 22 with LOCF (n=52, 51)	34.5 minutes Interval 22.0 to 50.0	63.00 minutes Interval 35.0 to 115.0

SECONDARY outcome

Timeframe: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing

Population: ITT

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.

Outcome measures

Measure	Albuterol n=51 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
Participant Responses: Percentage of Participants With a >=15% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 Day 1 (n=51, 51)	17.6 percentage of participants	9.8 percentage of participants
Participant Responses: Percentage of Participants With a >=15% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 Day 22 (n=51, 47)	17.6 percentage of participants	6.4 percentage of participants

SECONDARY outcome

Timeframe: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing

Population: ITT

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.

Outcome measures

Measure	Albuterol n=51 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
Participant Responses: Percentage of Participants With a >=12% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 Day 1 (n=51, 51)	33.3 percentage of participants	13.7 percentage of participants
Participant Responses: Percentage of Participants With a >=12% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 Day 22 (n=51, 47)	29.4 percentage of participants	14.9 percentage of participants

SECONDARY outcome

Timeframe: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing

Population: ITT

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.

Outcome measures

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
Participant Responses: Percentage of Participants With a >=15% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 Day 1 (n=52, 51)	44.2 percentage of participants	19.6 percentage of participants
Participant Responses: Percentage of Participants With a >=15% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 Day 22 (n=51, 47)	41.2 percentage of participants	23.4 percentage of participants

SECONDARY outcome

Timeframe: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing

Population: ITT

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.

Outcome measures

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
Participant Responses: Percentage of Participants With a >=12% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 Day 1 (n=52, 51)	57.7 percentage of participants	25.5 percentage of participants
Participant Responses: Percentage of Participants With a >=12% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 Day 22 (n=51, 47)	56.9 percentage of participants	29.8 percentage of participants

SECONDARY outcome

Timeframe: Weeks 1, 2, 3

Population: ITT population.

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

Outcome measures

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3 Week 1 (N=50, N=50)	0.370 units on a scale Standard Error 0.070	0.442 units on a scale Standard Error 0.070
Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3 Week 2 (N=50, N=49)	0.376 units on a scale Standard Error 0.070	0.547 units on a scale Standard Error 0.071
Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3 Week 3 (N=47, N=48)	0.336 units on a scale Standard Error 0.072	0.474 units on a scale Standard Error 0.071

SECONDARY outcome

Timeframe: Run-in (Days -21 to -1), Weeks 1, 2, 3

Population: ITT population

Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night.

Outcome measures

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication Run-In (N=52, N=51)	1.15 awakenings/week Standard Deviation 2.97	1.06 awakenings/week Standard Deviation 2.44
The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication Week 1 (N=51, N=50)	1.14 awakenings/week Standard Deviation 3.25	1.00 awakenings/week Standard Deviation 2.84
The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication Week 2 (N=51, N=49)	1.16 awakenings/week Standard Deviation 3.82	0.73 awakenings/week Standard Deviation 1.97
The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication Week 3 (N=49, N=48)	0.65 awakenings/week Standard Deviation 2.21	1.33 awakenings/week Standard Deviation 3.13

SECONDARY outcome

Timeframe: Weeks 1, 2, 3

Population: ITT population

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.

Outcome measures

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning Week 1 (N=51, N=50)	229.65 Liters/minute Standard Error 4.800	219.72 Liters/minute Standard Error 4.854
Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning Week 2 (N=51, N=49)	229.90 Liters/minute Standard Error 4.800	218.97 Liters/minute Standard Error 4.870
Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning Week 3 (N=49, N=48)	231.28 Liters/minute Standard Error 4.820	221.73 Liters/minute Standard Error 4.880

SECONDARY outcome

Timeframe: Weeks 1, 2, 3

Population: ITT population

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.

Outcome measures

Measure	Albuterol n=52 Participants Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days.	Placebo n=51 Participants Placebo-HFA-MDI four times a day for 21 days.
Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3 Week 3 (N=49, N=48)	0.078 Number of puffs per day Interval 0.01 to 0.146	0.088 Number of puffs per day Interval 0.013 to 0.163
Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3 Week 1 (N=51, N=50)	0.074 Number of puffs per day Interval 0.009 to 0.138	0.075 Number of puffs per day Interval 0.011 to 0.139
Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3 Week 2 (N=51, N=49)	0.084 Number of puffs per day Interval 0.011 to 0.158	0.088 Number of puffs per day Interval 0.013 to 0.163

Adverse Events

Albuterol

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Albuterol n=52 participants at risk Albuterol-HFA-MDI 180 mcg, four times a day	Placebo n=51 participants at risk Placebo HFA-MDI four times a day for 21 days.
Infections and infestations Nasopharyngitis	7.7% 4/52 • Number of events 4 • Days 1-22	0.00% 0/51 • Days 1-22
Nervous system disorders Headache	5.8% 3/52 • Number of events 4 • Days 1-22	9.8% 5/51 • Number of events 6 • Days 1-22

Additional Information

Teva Study Physician

Teval Global Respiratory Research LLC

Phone: 215-293-6482

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER