A 12-week Safety and Efficacy Study of Beclomethasone Dipropionate (80 and 160 mcg/Day) Delivered Via Breath-Actuated Inhaler (BAI) in Patients >=12 Years Old With Persistent Asthma

The primary efficacy variable was the standardized baseline-adjusted trough morning (pre-dose and pre-rescue bronchodilator) FEV1 AUEC(0-12wk). Pulmonary function measurements such as FEV1 were obtained electronically by spirometry at the randomization visit (Day 1), each treatment visit (Weeks 2, 4, 8 and 12) and any unscheduled visit (such as the early termination visit). This summary is based on observed values recorded as 'best attempt'.

The least-square (LS) means, difference of LS means and its 95% confidence interval (CI), and p-value represent the results obtained from the analysis of covariance with covariate adjustment for baseline, sex, age, current asthma therapy, and treatment.

Change from baseline in the weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) PEF by handheld spirometer over the 12-week treatment period.

PEF were determined twice daily, in the morning and in the evening, before administration of study drug or rescue medications. A handheld spirometer was provided to patients and used to determine the morning and evening PEF throughout the study. The spirometer was programmed to record the highest PEF obtained from 3 valid attempts.

Baseline was defined as the average of recorded trough morning PEF assessments over the 7 days prior to the first dose of double-blind study treatment, including the morning assessment at the randomization visit.

The LS means, difference of LS means and its 95% confidence interval, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week, and treatment by week interaction.

A hand-held peak flow meter was provided to patients at the screening visit and used to determine the morning and evening PEF throughout the course of the study. The patient recorded the highest value of 3 measurements obtained in the morning and evening in the patient diary.

Baseline in evening PEF is defined as the average of recorded evening PEF assessments over the 7-day window before randomization.

The LS means, difference of LS means and its 95% confidence interval, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week, and treatment by week interaction.

Change from baseline in the use of rescue medication, albuterol/salbutamol, during the treatment period offers an indication of asthma control.

The LS means, difference of LS means and its 95% CI, and p-value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week and treatment by week interaction.

Baseline was defined as the average of recorded daily usage of albuterol/salbutamol inhalation aerosol over the 7 days prior to the first dose of double-blind study treatment, including morning usage at the randomization visit.

Asthma symptom scores were recorded in the patient's diary each morning and evening before determining FEV1 and PEF and before administration of study or rescue medications.

The Daytime Symptom Score was recorded in the evening on a scale of 0 (No symptoms during the day) to 5 (Symptoms so severe that I could not go to work or perform normal daily activities) plus the Nighttime Symptom Score in the morning on a scale of 0 (No symptoms during the night) to 4 (Symptoms so severe that I did not sleep at all) for a total score range of 0-9.

Baseline was defined as the average of recorded daily asthma symptom scores (average of daytime and nighttime score) over the 7 days prior to the first dose of study treatment, including the morning assessment at the randomization visit.

The LS means, difference of LS means and its 95% CI, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy,

The time to patient study drug treatment withdrawal due to worsening asthma was defined as the number of days elapsed from the date of randomization to the date of withdrawal due to meeting stopping criteria. Alert criteria for individual patients with worsening asthma were designed to ensure patient safety. The investigator determined whether the patient's overall clinical picture is consistent with worsening asthma and if the patient should be withdrawn from study drug treatment (but not the study) and be placed on appropriate asthma therapy in the interest of patient safety.

An example of alert criteria is:

• FEV1 as measured at the study center is below the FEV1 stability limit value calculated at randomization visit (Day 1).
• Other criteria as defined in the protocol.

A count of participants who were withdrawn from the study due to meeting stopping criteria. Alert criteria for individual patients with worsening asthma were designed to ensure patient safety. The investigator determined whether the patient's overall clinical picture is consistent with worsening asthma and if the patient should be withdrawn from study drug treatment (but not the study) and be placed on appropriate asthma therapy in the interest of patient safety.

An example of alert criteria is:

• FEV1 as measured at the study center is below the FEV1 stability limit value calculated at randomization visit (Day 1).
• Other criteria as defined in the protocol.

An adverse event was defined 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 inability to carry out usual 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 1 of the outcomes listed in this definition.

Criteria for the select vital signs that showed a potentially clinically relevant abnormal result are:

• Sitting systolic BP (low); <=90 mm Hg and decrease of >=20 mm Hg from baseline
• Sitting diastolic BP (high): >=105 mm Hg and increase of >=15 mm Hg from baseline

Baseline is defined as the last available assessment prior to the first dose of double-blind study treatment (usually Day 1 predose).

Oropharyngeal examinations were performed at every visit by a qualified healthcare professional: during treatment visits are summarized. Any visual evidence of oral candidiasis during the treatment period of the study was evaluated by obtaining and analyzing a swab of the suspect area for culturing. Appropriate therapy was to be initiated immediately at the discretion of the investigator and was not to be delayed for culture confirmation.