Efficacy and Safety of 2 Doses of Tiotropium Respimat® Co... | NCT01634152

ID	Type	Description	Link
2011-001777-43	EudraCT Number	EudraCT

Status Module

Name	Class
Pfizer	INDUSTRY

Label	Type	Intervention Names
Placebo QD	Placebo Comparator	Drug: Placebo
Tiotropium low dose QD	Experimental	Drug: Tiotropium low dose mcg
Tiotropium medium dose QD	Experimental	Drug: Tiotropium high dose

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	2 actuations once daily in the evening	Placebo QD
Tiotropium low dose mcg

Measure	Description	Time Frame
FEV1 Peak(0-3h) Change From Baseline	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. Measured values presented are actually adjusted means.	Baseline and 12 weeks

Measure	Description	Time Frame
Trough FEV1 Change From Baseline	Change from baseline in Trough (pre-dose) Forced expiratory volume in 1 second (FEV1) measured at week 12. Measured values presented are actually adjusted means.	Baseline and 12 weeks
FVC Peak(0-3h) Change From Baseline

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Inclusion criteria are:

All patients' parent(s) (or legal guardian) must sign and date an informed consent prior to participation in the trial. 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.
Male or female patients between 6 and 11 years of age.
All patients must have at least a 6-month history of asthma.
All patients must have been on maintenance treatment with an inhaled corticosteroid either at stable high dose in combination with another controller medication, OR at stable medium dose in combination with two other controller medications, for at least 4 weeks before Visit 1.
All patients must be symptomatic (partly controlled) at Visit 1 and prior to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ-IA) mean score >= 1.5.
All patients must have a pre-bronchodilator forced expiratory volume in one second (FEV1) >= 60% and <= 90% of predicted normal at Visit 1.
Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator, considered as 100%) as compared to Visit 2 (pre-dose) must be within ± 30%.
All patients must confirm the diagnosis of asthma by bronchodilator reversibility at Visit 1, resulting in an increase in FEV1 of >= 12% 15 to 30 minutes after 200 mcg salbutamol/albuterol.
Patients must be able to use the Respimat inhaler correctly.
Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of electronic diary/peak flow meter (diary compliance of at least 80% is required).

Exclusion criteria:

Exclusion criteria are:

Patients with a significant disease other than asthma.
Patients with a clinically relevant abnormal haematology or blood chemistry at screening.
Patients with a history of congenital or acquired heart disease, or patients who have been hospitalised for cardiac syncope or failure during the past year.
Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year.
Patients with a malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.
Patients with known active tuberculosis.
Patients who have undergone thoracotomy with pulmonary resection.
Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the six weeks prior to Visit 1.
Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the inhalation solution used with the Respimat inhaler.
Pregnant or nursing female patients, including postmenarchal girls with a positive urine pregnancy test at Visit 1.
Postmenarchal girls of child-bearing potential not using a highly effective method of birth control.
Patients who have been treated with systemic corticosteroids within four weeks prior to Visit 1.
Patients who have been treated with systemic beta-adrenergics within four weeks prior to Visit 1.
Patients who have been treated with oral beta-blocker medication within four weeks prior to Visit 1 and/or during the screening period.
Patients who have been treated with inhaled long-acting anticholinergics or systemic anticholinergic treatment within four weeks prior to Visit 1 and/or during the screening period, or who have been treated with inhaled short-acting anticholinergics within two weeks prior to Visit 1.
Patients who have been treated with short-acting theophylline preparations within two weeks prior to Visit 1.
Patients who have been treated with non-approved and according to international guidelines not recommended experimental drugs for routine asthma therapy within four weeks prior to Visit 1 and/or during the screening period.
Patients who have taken an investigational drug within six half lives according to the investigator's information, or four weeks (whichever is greater) prior to Visit 1 and/or during the screening period.
Patients who have previously been randomised in this trial or are currently participating in another trial.
Patients with any acute asthma exacerbation or respiratory tract infection in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2. In case of an asthma deterioration occurring in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2, the visit must be postponed.
Patients requiring six or more puffs of rescue medication per day on more than two consecutive days in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2. In case of an asthma deterioration occurring in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2, the visit must be postponed.
Patients who are unable to comply with medication restrictions prior to Visit 1 and/or prior to Visit 2.
Patients with a known narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated.
Patients with moderate to severe renal impairment, as defined by a creatinine clearance <50 mL/min/1.73 m2 BSA, as tiotropium is a predominantly renally excreted drug.

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
205.446.01014 Boehringer Ingelheim Investigational Site		Rolling Hills Estates	California		United States

ID	Title	Description
FG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
FG001	Tio R2.5

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

FEV1 Peak(0-3h) Change From Baseline

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.

Measured values presented are actually adjusted means.

Full Analysis Set (FAS) was the same as the treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. Missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Litres

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Units	Counts
Participants	OG000130 OG001135 OG002128

Title

Denominators

Categories

Title	Measurements
	OG0000.252± 0.025 OG0010.287± 0.025 OG0020.391± 0.026

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Stepwise testing of the null hypothesis was used to test the efficacy of Tio R5 and then Tio R2.5, each over placebo. The analysis was performed in a stepwise manner, firstly for this endpoint, then Trough FEV1. Each step was only considered confirmatory if all previous steps were successful.	Mixed Models Analysis	Repeated measures restricted maximum likelihood model	0.2724		Mean Difference (Net)	0.035	Standard Error of the Mean	0.032	2-Sided	95	-0.028	0.099			Difference calculated as Tio R2.5 minus placebo	No

Secondary

Trough FEV1 Change From Baseline

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

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Litres

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

FVC Peak(0-3h) Change From Baseline

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.

The measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Litres

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Trough FVC Change From Baseline

Change from baseline in Trough (pre-dose) FVC measured at week 12.

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Litres

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Units

Secondary

FEV1 AUC (0-3h) Change From Baseline

Change from baseline of area under the curve (AUC) from 0 to 3 hours 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).

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Litres

Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

FVC AUC (0-3h) Change From Baseline

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

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Litres

Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

FEV1 Change From Baseline at Each Individual Timepoint

Forced expiratory volume in one second (FEV1) change from baseline at each individual timepoint.

The measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Litres

Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

FVC Change From Baseline at Each Individual Timepoint

FVC change from baseline at each individual timepoint.

The measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Litres

Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Control of Asthma as Assessed by ACQ-IA Total Score

Change from baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) total score measured at week 12.

The ACQ-IA is a scale containing 7 questions. Each question has a 7 point scale which ranges from 0 to 6. A score of 0 corresponds to no impairment and a score of 6 corresponds to maximum impairment. ACQ-IA total score is calculated as the mean of the responses to all 7 questions.

The measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Units on a scale

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

ACQ-IA Total Score Responders

Responder categories based on the ACQ-IA total score after 12 weeks of treatment. Analysis was performed using the following categories and definitions: responder (change from trial baseline ≤-0.5), no change (-0.5 \

FAS, missing data for patients not withdrawn from the study were either categorised as no change or based on available data, withdrawn patients were imputed based upon discontinuation reason.

Posted

Number

Percentage of participants

12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5

Secondary

Use of PRN Rescue Medication Per Day

Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used per day (24 hour period) based on the weekly mean at week 12.

The measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Number of puffs of rescue medication

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Use of PRN Rescue Medication During the Daytime

Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during the daytime based on the weekly mean at week 12.

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Number of puffs of rescue medication

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Use of PRN Rescue Medication During the Night-time

Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during the night-time based on the weekly mean at week 12.

Measured values presented are actually adjusted means

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Number of puffs of rescue medication

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Peak Expiratory Flow (PEF) a.m. Change From Baseline

Change from baseline in the morning (a.m.) peak expiratory flow based on the weekly mean at week 12.

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

L/min

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Peak Expiratory Flow (PEF) p.m. Change From Baseline

Change from baseline in the evening (p.m.) peak expiratory flow based on the weekly mean at week 12.

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

L/min

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Peak Expiratory Flow (PEF) Variability Change From Baseline

Change from baseline in the peak expiratory flow variability based on the weekly mean at week 12.

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Percentage of PEF

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

FEV1 a.m. Change From Baseline

Change from baseline in morning (a.m.) FEV1 based on the weekly mean at week 12.

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Litres

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

FEV1 p.m. Change From Baseline

Change from baseline in evening (p.m.) FEV1 based on the weekly mean at week 12.

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Litres

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Change From Baseline in Nighttime Awakenings

Change from baseline in nighttime awakenings based on the weekly mean at week 12.

Nighttime awakenings was assessed by the question "Did you wake up during the night due to your asthma?" from the e-diary. Scores range from 1 (did not wake up) to 5 (was awake all night).

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Units on a scale

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Change From Baseline in Morning Asthma Symptoms

Change from baseline in morning asthma symptoms based on the weekly mean at week 12.

Morning asthma symptoms was assessed by the question "how were your asthma symptoms this morning?" from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms).

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Units on a scale

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Change From Baseline in Daytime Asthma Symptoms

Change from baseline in daytime asthma symptoms based on the weekly mean at week 12.

Daytime asthma symptoms was assessed by the question "how were your asthma symptoms during the day?" from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms).

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Units on a scale

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Change From Baseline in Daytime Activity Limitations

Change from baseline in daytime activity limitations based on the weekly mean at week 12.

Daytime activity limitations was assessed by the question "how limited were you in your activities today because of your asthma?" from the e-diary. Scores range from 1 (not limited) to 5 (totally limited).

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Units on a scale

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Change From Baseline in Daytime Experiences of Shortness of Breath

Change from baseline in daytime experiences of shortness of breath based on the weekly mean at week 12.

Daytime experiences of shortness of breath was assessed by the question "how much shortness of breath did you experience during the day" from the e-diary. Scores range from 1 (none) to 5 (a very great deal).

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Units on a scale

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Change From Baseline in Daytime Experiences of Wheeze or Cough

Change from baseline in daytime experiences of wheeze or cough based on the weekly mean at week 12.

Daytime experiences of wheeze or cough was assessed by the question "did you experience wheeze or cough during the day?" from the e-diary. Scores range from 1 (not at all) to 5 (all the time).

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Units on a scale

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

Secondary

Change From Baseline in Asthma Symptom-free Days

Change from baseline in asthma symptom-free days based on the weekly mean at week 12.

A day was considered as an asthma symptom-free day if there were no symptoms reported via the e-Diary and no use of rescue medication reported via the eDiary during that day.

Measured values presented are actually adjusted means.

FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.

Posted

Mean

Standard Error

Days

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
OG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.	2	134	49	134
EG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.	2	136	36	136
EG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.	4	130	35	130

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Appendicitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected134 at risk EG0010 affected136 at risk EG0021 affected130 at risk
Epilepsy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected134 at risk EG0011 affected136 at risk EG0020 affected130 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected134 at risk EG0011 affected136 at risk EG0023 affected130 at risk
Asthmatic crisis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected134 at risk EG0010 affected136 at risk EG0020 affected130 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00011 affected134 at risk EG0016 affected136 at risk EG0026 affected130 at risk
Peak expiratory flow rate decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG00020 affected134 at risk EG00115 affected136 at risk EG00215 affected130 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00029 affected134 at risk EG00120 affected136 at risk EG00222 affected130 at risk

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Term
D012602	Scopolamine Derivatives
D014326	Tropanes
D053961	Azabicyclo Compounds
D001372	Aza Compounds
D009930	Organic Chemicals
D000470	Alkaloids
D006571	Heterocyclic Compounds
D019086	Bridged Bicyclo Compounds, Heterocyclic
D006572	Heterocyclic Compounds, Bridged-Ring

ID	Title	Description
BG000	Placebo Respimat	Inhalation of placebo solution (2 puffs) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
BG001	Tio R2.5	Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
BG002	Tio R5	Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 12 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
BG003	Total	Total of all reporting groups