A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP TRIAL TO EVALUATE EFFICACY AND SAFETY OF TIOTROPIUM INHALATION SOLUTION (2.5 µG AND 5 µG) DELIVERED VIA RESPIMAT® INHALER ONCE DAILY IN THE EVENING OVER 48 WEEKS IN CHILDREN (6 TO 11 YEARS OLD) WITH MODERATE PERSISTENT ASTHMA

INTERVENTION: PATIENT WILL BE ON TREATMENT WITH INHALED CORTICOIDS AS A CONTROLLER MAINTENANCE THERAPY FOR THEIR ASTHMA DURING THE WHOLE TRIAL. THE TRIAL DESIGN HAS BEEN SELECTED TO ALLOW ASSESSMENT OF SAFETY AND EFFICACY ON PULMONARY FUNCTION AND PATIENT‐REPORTED OUTCOMES OF TWO DOSES OF TIOTROPIUM COMPARED TO PLACEBO IN CHILDREN WITH MODERATE PERSISTENT ASTHMA NOT FULLY CONTROLLED, DESPITE OF ICS MAINTENANCE THERAPY. IN ADDITION, LONG TERM SAFETY DATA ARE COLLECTED. TO GUARANTEE RELIABILITY OF STUDY RESULTS, ONE PATIENT IN THREE WILL BE ON PLACEBO FOR THE DURATION OF THE TRIAL. FURTHER INFORMATION ON MEASURES UNDERTAKEN TO LIMIT POTENTIAL ISSUES RELATED TO THE USE OF PLACEBO ARE DESCRIBED IN SECTION 2.3 OF THIS PROTOCOL. A SUFFICIENT NUMBER OF PATIENTS OF EITHER SEX, 6 TO 11 YEARS OLD, WITH A DIAGNOSIS OF MODERATE PERSISTENT ASTHMA WILL BE ENROLLED IN THE STUDY TO ENSURE THAT AT LEAST 381 CHILDREN ARE ENTERED (RANDOMISED) IN THE TRIAL. RECRUITMENT WILL CONTINUE UNTIL 381 PATIENTS ARE. PATIENT RECRUITMENT WILL BE COMPETITIVE AND CARRIED OUT AT APPROXIMATELY 70‐80 INVESTIGATIONAL SITES. EACH SITE IS EXPECTED TO ENTER ´4 TO 5 PATIENTS ON AVERAGE. SITES WHICH DO NOT RECRUIT WILL BE CLOSED PREMATURELY, AND ADDITIONAL SITES COULD BE INITIATED. CONDITION: PRIMARY OUTCOME: Peak forced expiratory volume in one second response within 3 hours post dosing (FEV1 peak0‐3h response).; NAME OF THE RESULT: Peak forced expiratory volume in one second response within 3 hours post dosing (FEV1 peak0‐3h response).; USED MEASURING METHOD :Analysed using a restricted maximum likehood (REML)‐based Mixed Model Repeated Measures (MMRM).; PERIOD OF TIME WHERE THE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: After 24 weeks. SECONDARY OUTCOME: Area under the curve from zero to 3 hours of the forced expiratory volume in one second (FEV1) response and area under the curve from zero to 3 hours of the forced vital capacity (FVC) response. ; NAME OF THE RESULT: Area under the curve from zero to 3 hours of the forced expiratory volume in one second response and area under the curve from zero to 3 hours ofthe forced vital capacity response. ; USED MEASURING METHOD :Analysed using a restricted maximum likehood (REML)‐based Mixed Model Repeated Measures (MMRM). ; PERIOD OF TIME WHERE THE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE SECONDARY RESULT: 24 Weeks. INCLUSION CRITERIA: 1. ALL PATIENTS´ PARENT(S) (OR LEGAL GUARDIAN) MUST SIGN AND DATE AN INFORMED CONSENT CONSISTENT WITH ICH GCP GUIDELINES AND LOCAL LEGISLATION PRIOR TO PARTICIPATION IN THE TRIAL, I.E. PRIOR TO ANY STUDY PROCEDURES INCLUDING MEDICATION WASH‐OUT AND RESTRICTIONS. IN ADDITION, AN INFORMED ASSENT SUITABLE FOR THIS AGE GROUP HAS TO BE OBTAINED FROM PATIENTS. A SEPARATE INFORMED CONSENT/ASSENT IS REQUIRED FOR PHARMACOGENOMIC SAMPLING (CONSENT/ASSENT FOR PHARMACOGENOMIC SAMPLING IS NOT A PREREQUISITE FOR STUDY ENTRY). 2. MALE OR FEMALE PATIENTS BETWEEN 6 AND 11 YEARS OF AGE (AT DAY OF INFORMED CONSENT/ASSENT), 3. ALL PATIENTS MUST HAVE AT LEAST A 6‐MONTH HISTORY OF ASTHMA AT THE TIME OF ENROLMENT INTO THE TRIAL. 4. ALL PATIENTS MUST HAVE BEEN ON MAINTENANCE TREATMENT WITH AN INHALED CORTICOSTEROID AT A STABLE MEDIUM DOSE, EITHER AS MONO TREATMENT OR IN COMBINATION WITH ANOTHER CONTROLLER MEDICATION (E.G. A LABA OR A LEUKOTRIENE MODIFIER), FOR AT LEAST 4 WEEKS