A Phase II, randomised, double- blind, placebo controlled, cross-over efficacy and safety comparison of tiotropium 5 µg administered once daily (in the evening) and tiotropium 2.5 µg administered twice daily delivered by the Respimat® inhaler for four weeks versus placebo in patients with moderate persistent asthma

INTERVENTION: Trade Name: Spiriva Respimat 2.5 Mikrogramm‐Lösung zur Inhalation Product Name: Spiriva Respimat 2.5 mcg Product Code: Tiotropium Respimat Pharmaceutical Form: Inhalation vapour, solution CAS Number: 411207313 Current Sponsor code: Ba 679 Br Other descriptive name: TIOTROPIUM BROMIDE MONOHYDRATE Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 3.124‐ Pharmaceutical form of the placebo: Inhalation vapour* Route of administration of the placebo: Inhalation use Product Name: Tiotropium Respimat 1.25 mcg Product Code: Tiotropium Respimat 1.25 mcg Pharmaceutical Form: Inhalation vapour, solution CAS Number: 411207313 Current Sponsor code: Ba 679 Br Other descriptive name: TIOTROPIUM BROMIDE MONOHYDRATE Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 1.562‐ Pharmaceutical form of the placebo: Inhalation vapour* Route of administration of the placebo: Inhalation use CONDITION: moderate persistent asthma ; MedDRA version: 12.1 Level: LLT Classification code 10003553 Term: Asthma PRIMARY OUTCOME: Main Objective: Demonstrate 24 hour bronchodilator efficacy and safety of tiotropium 5 µg; administered once daily (in the evening) delivered by the Respimat® inhaler for four; weeks in comparison to placebo. Evaluate efficacy and safety of tiotropium 2.5 µg; administered twice daily delivered by the Respimat® inhaler for four weeks in; comparison to placebo and to tiotropium 5 µg administered once daily (in the; evening) delivered by the Respimat® inhaler for four weeks in patients with moderate persistent asthma. Primary end point(s): The primary efficacy variable will be the forced expiratory volume in one second (FEV1).; The primary endpoint is the FEV1 area under the curve (AUC) 0‐24 hours (AUC0‐24h) (L) determined at the end of each 4 week treatment period. All measurements will be performed in relation to evening (p.m.) dosing Secondary Objective: The effect on asthma control, nighttime awakenings and rescue medication use will be evaluated. INCLUSION CRITERIA: Outpatients with a history of asthma and a current diagnosis of moderate persistent asthma (according to GINA guideline) are eligible for inclusion if they fulfil all the inclusion criteria and none of the exclusion criteria. 1. All patients must sign and date an Informed Consent Form consistent with ICH‐GCP guidelines and local legislation prior to participation in the trial (i.e. prior to any trial procedures, including any pre‐trial washout of medications and medication restrictions for pulmonary function test at Visit 1). 2. Male or female patients aged at least 18 years but not more than 75 years. 3. All patients must have at least a 3 months history of asthma at the time of enrolment into the trial. The diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility (15 minutes after 400 µg salbutamol) resulting in a FEV1 increase of = 12% and = 200mL. 4. The initial diagnosis of asthma must have been made before the pati