Trial Outcomes & Findings for Efficacy and Safety of 2 Doses of Tiotropium Respimat Compared to Placebo in Adolescents With Severe Persistent Asthma (NCT NCT01277523)

NCT ID: NCT01277523

Last Updated: 2014-10-20

Results Overview

Change from baseline in peak forced expiratory volume in 1 second within the first 3 hours post dosing (FEV1 peak0-3) measured at week 12. Measured values presented are actually adjusted means.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 392 participants
• Primary outcome timeframe: Baseline and 12 weeks
• Results posted on: 2014-10-20

Participant Flow

Participant milestones

Measure	Placebo Respimat Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
Overall Study STARTED	135	127	130
Overall Study COMPLETED	132	126	130
Overall Study NOT COMPLETED	3	1	0

Reasons for withdrawal

Measure	Placebo Respimat Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
Overall Study Adverse Event	1	0	0
Overall Study Protocol Violation	2	0	0
Overall Study Other Reason not Defined	0	1	0

Baseline Characteristics

Efficacy and Safety of 2 Doses of Tiotropium Respimat Compared to Placebo in Adolescents With Severe Persistent Asthma

Baseline characteristics by cohort

Measure	Placebo Respimat n=135 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=127 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Total n=392 Participants Total of all reporting groups
Age, Continuous	14.1 years STANDARD_DEVIATION 1.7 • n=5 Participants	14.4 years STANDARD_DEVIATION 1.8 • n=7 Participants	14.3 years STANDARD_DEVIATION 1.6 • n=5 Participants	14.2 years STANDARD_DEVIATION 1.7 • n=4 Participants
Sex: Female, Male Female	56 Participants n=5 Participants	47 Participants n=7 Participants	47 Participants n=5 Participants	150 Participants n=4 Participants
Sex: Female, Male Male	79 Participants n=5 Participants	80 Participants n=7 Participants	83 Participants n=5 Participants	242 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: 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.

Change from baseline in peak forced expiratory volume in 1 second within the first 3 hours post dosing (FEV1 peak0-3) measured at week 12.

Measured values presented are actually adjusted means.

Outcome measures

Measure	Placebo Respimat n=132 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=126 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
FEV1 peak0-3 Change From Baseline	0.438 litres Standard Error 0.045	0.550 litres Standard Error 0.046	0.528 litres Standard Error 0.045

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: 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.

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.

Outcome measures

Measure	Placebo Respimat n=132 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=126 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
Trough FEV1 Change From Baseline	0.230 litres Standard Error 0.048	0.345 litres Standard Error 0.048	0.284 litres Standard Error 0.048

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: 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.

Change from baseline in Maximum forced vital capacity (FVC) measured within the first 3 hours after administration of trial medication (FVC peak0-3h) after 12 weeks of treatment.

The measured values presented are actually adjusted means.

Outcome measures

Measure	Placebo Respimat n=132 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=126 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
FVC peak0-3 Change From Baseline	0.279 Litres Standard Error 0.048	0.370 Litres Standard Error 0.049	0.342 Litres Standard Error 0.048

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Measure	Placebo Respimat n=132 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=126 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
FEV1 AUC (0-3h) Change From Baseline	0.336 Litres Standard Error 0.043	0.449 Litres Standard Error 0.043	0.423 Litres Standard Error 0.043

SECONDARY outcome

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

Population: 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.

Change from baseline of area under the curve (AUC) from 0 to 3 hours for FVC (Forced vital capacity) (FVC AUC0-3h) 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.

Outcome measures

Measure	Placebo Respimat n=132 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=126 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
FVC AUC (0-3h) Change From Baseline	0.175 litres Standard Error 0.045	0.262 litres Standard Error 0.047	0.227 litres Standard Error 0.046

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: 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.

Change from baseline in Asthma Control Questionnaire (ACQ) 6 score measured at week 12

The ACQ 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. ACQ6 score is calculated as the mean of the responses to the first 6 questions of the ACQ6.

The measured values presented are actually adjusted means.

Outcome measures

Measure	Placebo Respimat n=132 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=126 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
Control of Asthma as Assessed by ACQ6 Score.	1.144 units on a scale Standard Error 0.069	1.262 units on a scale Standard Error 0.071	1.197 units on a scale Standard Error 0.070

SECONDARY outcome

Timeframe: 12 weeks

Population: Full Analysis Set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. 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.

Responder rates based on the ACQ6 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 < change from trial baseline <0.5) and worsening (change from trial baseline >= 0.5).

The ACQ 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. ACQ6 is calculated as the mean of the responses to the first 6 questions of the ACQ6.

No statistical testing was performed on ACQ6 responders.

Outcome measures

Measure	Placebo Respimat n=135 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=127 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
ACQ6 Score Responders Responder	74.1 percentage of participants	74.0 percentage of participants	74.6 percentage of participants
ACQ6 Score Responders No Change	23.7 percentage of participants	19.7 percentage of participants	23.1 percentage of participants
ACQ6 Score Responders Worsening	2.2 percentage of participants	6.3 percentage of participants	2.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: 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.

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

The ACQ 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 total score is calculated as the mean of the responses to all 7 questions.

The measured values presented are actually adjusted means.

Outcome measures

Measure	Placebo Respimat n=132 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=126 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
Control of Asthma as Assessed by ACQ Total Score	1.234 units on a scale Standard Error 0.064	1.292 units on a scale Standard Error 0.066	1.270 units on a scale Standard Error 0.065

SECONDARY outcome

Timeframe: 12 weeks

Population: Full Analysis Set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. 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.

Responder rates based on the ACQ 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 <change from trial baseline <0.5) and worsening (change from trial baseline ≥0.5) No statistical testing was performed for ACQ total score responders.

The ACQ 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.

Outcome measures

Measure	Placebo Respimat n=135 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=127 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
ACQ Total Score Responders Responder	73.3 percentage of participants	74.8 percentage of participants	73.1 percentage of participants
ACQ Total Score Responders No Change	23.7 percentage of participants	22.0 percentage of participants	26.2 percentage of participants
ACQ Total Score Responders Worsening	3.0 percentage of participants	3.1 percentage of participants	0.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: 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 was imputed by the available data from the patient. Completely missing data were handled by the statistical model.

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

The measured values presented are actually adjusted means.

Outcome measures

Measure	Placebo Respimat n=131 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=124 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
Use of PRN Rescue Medication During the Day	-0.482 Number of puffs of rescue medication Standard Error 0.118	-0.483 Number of puffs of rescue medication Standard Error 0.122	-0.540 Number of puffs of rescue medication Standard Error 0.120

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: 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 was imputed by the available data from the patient. Completely missing data were handled by the statistical model.

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.

Outcome measures

Measure	Placebo Respimat n=131 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=124 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
Use of PRN Rescue Medication During the Daytime	-0.262 Number of puffs of rescue medication Standard Error 0.073	-0.295 Number of puffs of rescue medication Standard Error 0.075	-0.312 Number of puffs of rescue medication Standard Error 0.073

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: 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 was imputed by the available data from the patient. Completely missing data were handled by the statistical model.

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

Outcome measures

Measure	Placebo Respimat n=131 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=124 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=129 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
Use of PRN Rescue Medication During the Night-time	-0.180 Number of puffs of rescue medication Standard Error 0.064	-0.092 Number of puffs of rescue medication Standard Error 0.066	-0.159 Number of puffs of rescue medication Standard Error 0.065

SECONDARY outcome

Timeframe: 12 weeks

Population: 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.

Time in days to first severe asthma exacerbation during the 12 week treatment period. The median time to first severe asthma exacerbation was not calculable, so the number of patients who experienced a severe asthma exacerbation are presented for the measured values.

A severe asthma exacerbation was defined as a subgroup of all asthma exacerbations that required an initiation of treatment with systemic corticosteroids for at least 3 days or, in case of ongoing and pre-existing systemic corticosteroid therapy, requiring at least doubling of previous daily doses of systemic corticosteroids for at least 3 days.

Outcome measures

Measure	Placebo Respimat n=135 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=127 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
Time to First Severe Asthma Exacerbation During the 12-week Treatment Period.	1 participants	1 participants	2 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: 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.

Time in days to first asthma exacerbation during the 12 week treatment period. The median time to first asthma exacerbation was not calculable, so the number of patients who experienced an asthma exacerbation are presented for the measured values.

Outcome measures

Measure	Placebo Respimat n=135 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=127 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
Analysis of Time to First Asthma Exacerbation During the 12 Week Treatment Period.	25 participants	18 participants	15 participants

SECONDARY outcome

Timeframe: From first drug administration until 30 days after last drug intake, up to 142 days

Population: Treated set which included all randomised patients who were dispensed and received, at least one documented dose of trial medication.

Clinically relevant abnormalities for physical examination, ECG, vital signs and laboratory tests. New abnormal findings or worsening of baseline conditions were reported as adverse events.

Outcome measures

Measure	Placebo Respimat n=135 Participants Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=127 Participants Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 Participants Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
Clinically Relevant Abnormalities for Physical Examination, ECG, Vital Signs and Laboratory Tests Peak expiratory flow rate decreased	9.6 percentage of participants	7.1 percentage of participants	3.8 percentage of participants
Clinically Relevant Abnormalities for Physical Examination, ECG, Vital Signs and Laboratory Tests Blood glucose decreased	0.0 percentage of participants	0.8 percentage of participants	0.0 percentage of participants

Adverse Events

Placebo Respimat

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Tio R2.5

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

Tio R5

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo Respimat n=135 participants at risk Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=127 participants at risk Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 participants at risk Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
Infections and infestations Pyoderma	0.00% 0/135 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.	0.79% 1/127 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.	0.00% 0/130 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/135 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.	0.00% 0/127 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.	0.77% 1/130 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/135 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.	0.00% 0/127 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.	0.77% 1/130 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/135 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.	0.79% 1/127 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.	0.00% 0/130 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.

Other adverse events

Measure	Placebo Respimat n=135 participants at risk Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R2.5 n=127 participants at risk Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.	Tio R5 n=130 participants at risk Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care.
Investigations Peak expiratory flow rate decreased	9.6% 13/135 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.	7.1% 9/127 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.	3.8% 5/130 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.
Respiratory, thoracic and mediastinal disorders Asthma	10.4% 14/135 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.	11.0% 14/127 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.	10.8% 14/130 • From first drug administration until 30 days after last drug intake, up to 142 days Treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication.

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

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