Evaluation of Tiotropium 2.5 and 5 mcg Once Daily Delivered Via the Respimat® Inhaler Compared to Placebo in 1 to 5 Year Old Patients With Persistent Asthma

Change from baseline in peak Forced expiratory volume in 1 second within the first 3 hours post dosing (FEV1 peak (0-3h)) measured at week 12

Time frame: 10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12

Population: Full analysis set including only 5 years olds capable of providing technically acceptable pulmonary function tests (PFTs). No imputation for missing data was employed.

Change from baseline in the weekly mean combined daytime asthma symptom score as assessed by the Paediatric Asthma Caregivers Diary (PACD) in the last week of the 12 week treatment period. The PACD is a diary designed to evaluate daily asthma symptoms in children aged 2-5 years. The diary consists of three questions to be answered each morning, when the child wakes up, and seven questions to be answered each evening, right after the child goes to bed for the night. A week was defined as 7 days. The combined daytime score is the average of scores from questions 4 - 7 in the diary which are questions regarding severity of cough, wheezing, trouble breathing and interference with activities, scores for each question range from 0 (best) to 5 (worst). The week 12 weekly mean is the mean of the responses for each day averaged over the 7 days in week 12, so combined daytime asthma symptom scores also range from 0 (best) to 5 (worst). The measured values presented are adjusted means.

Time frame: Baseline and 12 weeks

Population: Full analysis set, which included all randomised patients who received at least one dose of trial medication, including patients with available endpoint data at week 12. Missing data in a week was imputed by the available data from the patient during that week, for weeks where data was completely missing no imputation was employed.

Change from baseline of area under the curve (AUC) from 0 to 3 h for FEV1 (FEV1 AUC 0-3h) after 12 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h).

Time frame: 10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12

Population: Full analysis set including only 5 years olds capable of providing technically acceptable pulmonary function tests (PFTs). No imputation for missing data was employed.

Change from baseline of area under the curve (AUC) from 0 to 3 h for FVC (FVC AUC0-3h) after 12 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h).

Time frame: 10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12

Population: Full analysis set including only 5 years olds capable of providing technically acceptable pulmonary function tests (PFTs). No imputation for missing data was employed.

Change from baseline in maximum forced vital capacity (FVC) measured within the first 3 hours after administration of trial medication (FVC peak (0-3h)) after 12 weeks of treatment.

Time frame: 10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12

Population: Full analysis set including only 5 years olds capable of providing technically acceptable pulmonary function tests (PFTs). No imputation for missing data was employed.

Change from baseline in individual FEV1 measurements at each timepoint after 12 weeks

Time frame: Baseline and 12 weeks

Population: Full analysis set including only 5 years olds capable of providing technically acceptable pulmonary function tests (PFTs). No imputation for missing data was employed.

Change from baseline in individual FVC measurements at each timepoint after 12 weeks

Time frame: Baseline and 12 weeks

Population: Full analysis set including only 5 years olds capable of providing technically acceptable pulmonary function tests (PFTs). No imputation for missing data was employed.

Change from baseline in Trough (pre-dose) Forced expiratory volume in 1 second (FEV1) measured at week 12.

Time frame: Baseline and 12 weeks

Population: Full analysis set including only 5 years olds capable of providing technically acceptable pulmonary function tests (PFTs). No imputation for missing data was employed.

Change from baseline of trough (pre-dose) forced vital capacity (FVC) measured 10 min before the administration of trial medication after 12 weeks of treatment.

Time frame: Baseline and 12 weeks

Population: Full analysis set including only 5 years olds capable of providing technically acceptable pulmonary function tests (PFTs). No imputation for missing data was employed.

Change from baseline in the weekly mean nighttime awakenings due to asthma symptoms as assessed by the PACD, in the last week of the 12 week treatment period. The weekly mean was calculated as the average of the weekly scores for the question Did your child wake up during the night due to his/her asthma? The question was answered on a 5-point verbal rating scale, with scores ranging from 1 (did not wake up) to 5 (was awake all night). A week was defined as 7 days. The measured values presented are adjusted means

Time frame: Baseline and 12 weeks

Population: Full analysis set, including patients with available endpoint data at week 12. Missing data in a week was imputed by the available data from the patient during that week, for weeks where data was completely missing no imputation was employed.

Change from baseline in the weekly mean overnight asthma symptom score response as assessed by the PACD in the last week of the 12 week treatment period. The overnight score is the score from the following question in the PACD, How much did your child cough last night after your child was put to bed for the night until he/she awoke this morning?. This endpoint was determined only for patients with 2 or more nights with symptoms per week during the baseline period. In this case, the baseline period is the 7 days used to derive the baseline value. A patient has a night with symptoms if the question was answered with scores 1, 2, 3, 4 or 5 or the patient received β-Agonist at least one time since he/she went to bed. A week was defined as 7 days. Scores range from 0 (best) to 4 (worst), a value of 5 indicates severity of symptoms is unknown. The measured values presented are adjusted means

Time frame: Baseline and 12 weeks

Population: Full analysis set, including patients with available endpoint data at week 12. Missing data in a week was imputed by the available data from the patient during that week, for weeks where data was completely missing no imputation was employed.

Weekly Percentage of days without asthma symptoms at week 12. A day without asthma symptoms was defined as a day during which the patient experienced no asthma symptoms, did not use rescue medication (salbutamol/albuterol) and had no asthma exacerbation/worsening requiring systemic corticosteroids, or unscheduled visits to a doctor's office, emergency department, or hospital. A week was defined as 7 days. The measured values presented are adjusted means

Time frame: 12 weeks

Population: Full analysis set, including patients with available endpoint data at week 12. Missing data in a week was imputed by the available data from the patient during that week, for weeks where data was completely missing no imputation was employed.

Weekly percentage of days with use of salbutamol (albuterol) rescue medication at week 12. A week was defined as 7 days.

Time frame: 12 weeks

Population: Full analysis set, including patients with available endpoint data at week 12. Missing data in a week was imputed by the available data from the patient during that week, for weeks where data was completely missing no imputation was employed.