Albuterol Spiromax

Following measurement of the baseline FEV1 and dose administration on Days 1 and 22, FEV1 values (highest of 3 acceptable maneuvers) will be obtained at 5 (±2), 15 (±5), 30 (±5), 45 (±5), 60 (±10), 120 (±10), 240 (±10), and 360 (±10) minutes after the completion of dosing. Predicted FEV1 values were computed and adjusted for age, height, and gender according to Eigen et al (Eigen et al 2001) for participants 4 to 5 years of age and to Quanjer et al (Quanjer et al 1995) for participants aged 6 to 11 years using ATS criteria (American Thoracic Society/European Respiratory Society Statement 2007).

The purpose of the study is to determine if the dose counter on Albuterol Spiromax is counting accurately; accuracy is determined by concordance/agreement between patient-reported Albuterol Spiromax counter readings and patient-reported dose cycles recorded in patient diaries. This outcome measures how often the dose cycle was not counted: the participant completes a full dose cycle (opens the mouthpiece cap, inhales the medication, and closes the mouthpiece cap) but the counter display does not advance (i.e., does not count down) within a dosing session. The discrepancy rate was calculated as "number of discrepancies/total number of dose cycles" \*200.

A centralized spirometry data collection system was used to reduce FEV1 variability between and within patients and between each participating study center. The percentage fall was defined as 100\*(baseline-post baseline)/baseline. The baseline FEV1 is the test day FEV1 measured 5 minutes before the exercise challenge (30 minutes postdose). FEV1 post exercise challenge were measured 5 (±5), 10 (±5), 15 (±5), 30 (±5), and 60 (±10) minutes after completion of the exercise challenge. The exercise challenge consisted of the participant running on a motor-driven treadmill (with adjustable speed and incline). The treadmill was set at a speed and incline sufficient to increase the participant's heart rate to ≥80% of the maximum rate for age (220 bpm-age in years) for a period of either 6, 7, or 8 minutes using a stepped-exercise protocol in accordance with ATS guidelines (American Thoracic Society 2000). Conditions were repeated for subsequent challenges.

FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average (by the trapezoidal rule) of FEV1 AUC 0-6 measures adjusted for the baseline measure (i.e., change from baseline at each timepoint) recorded on days 1, 8 and 85 of the treatment period. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.

Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

A standard 12-lead ECG was performed at screening, week 12, and week 52 or early termination/discontinuation. The ECG recording methods were centralized and standardized across all study participants. A centralized cardiologist was responsible for providing all ECG interpretations.

Participants were seated at least 2 minutes before blood pressure measurements were obtained by either an electronic or manual sphygmomanometer. Week 12 values represent change from Week 0. Week 52 values represent change from Week 12.

Participants were seated at least 2 minutes before pulse measurements were obtained by radial pulse. Week 12 values represent change from Week 0. Week 52 values represent change from Week 12.

The physical exam was performed by a qualified healthcare professional, and when possible, the same qualified healthcare professional that performed the physical examination at study screening performed all the scheduled physical examinations. Abnormalities and clinical relevance were determined by the qualified healthcare professional. HEENT = head, eyes, ears, nose, throat

Percent predicted FEV1: measured FEV1 as a percent of the "predicted values" for the patients of similar characteristics. Predicted FEV1 values were computed and adjusted for age, height, and gender for patients aged 4-5 years (Eigen et al 2001) and for patients aged 6-11 years (Quanjer et al 1995) using ATS/European Thoracic Society (ERS) criteria applicable to pediatric patients (ATS/ERS 2007). The percent predicted FEV1 (PPFEV1) area under the curve (AUC)0-6 was calculated using the linear trapezoidal rule, and baseline adjustment was made by subtracting the average of the 2 pre-dose PPFEV1 values from each post-dose PPFEV1 determination.

FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day. The first baseline spirometry was obtained between 6-11 AM. The highest FEV1 value from two acceptable values was captured for calculation of the efficacy endpoints. Assessments were obtained at approximately 0.5 hours and immediately before dosing, and 5 minutes, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5 and 6 hours after completion of dosing.

Blood samples for plasma albuterol concentration determination will be drawn 5 (±2) minutes prior to dosing and at 30 (±2), 60 (±5), 120 (±10), 360 (±10), and 600 (±10) minutes after the completion of dosing.

Blood samples for plasma albuterol concentration determination will be drawn 5 (±2) minutes prior to dosing and at 30 (±2), 60 (±5), 120 (±10), 360 (±10), and 600 (±10) minutes after the completion of dosing.