Trial Outcomes & Findings for Evaluation of Tiotropium 5 µg/Day Delivered Via the Respimat® Inhaler Over 48 Weeks in Patients With Severe Persistent Asthma on Top of Usual Care (Study I) (NCT NCT00772538)

Results Overview

Peak FEV1 0-3h response was defined as the difference between the maximum FEV1 measured within the first 3 hours post dosing after a treatment period of 24 weeks and the FEV1 baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

459 participants

Primary outcome timeframe

Baseline and 24 weeks

Results posted on

2014-08-18

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Patients treated with matching placebo	Tio R5 Patients treated with tiotropium inhalation solution 5 microgram qd
Overall Study STARTED	222	237
Overall Study COMPLETED	202	211
Overall Study NOT COMPLETED	20	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Patients treated with matching placebo	Tio R5 Patients treated with tiotropium inhalation solution 5 microgram qd
Overall Study Adverse Event	6	6
Overall Study Protocol Violation	3	3
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Subject	3	8
Overall Study Lack of Efficacy	0	1
Overall Study Other	7	7

Baseline Characteristics

Evaluation of Tiotropium 5 µg/Day Delivered Via the Respimat® Inhaler Over 48 Weeks in Patients With Severe Persistent Asthma on Top of Usual Care (Study I)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd	Total n=459 Participants Total of all reporting groups
Age, Continuous	53.9 Years STANDARD_DEVIATION 12.8 • n=5 Participants	52.9 Years STANDARD_DEVIATION 12.4 • n=7 Participants	53.4 Years STANDARD_DEVIATION 12.6 • n=5 Participants
Sex: Female, Male Female	143 Participants n=5 Participants	146 Participants n=7 Participants	289 Participants n=5 Participants
Sex: Female, Male Male	79 Participants n=5 Participants	91 Participants n=7 Participants	170 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 24 weeks

Population: All patients from Full Analysis Set (FAS) FAS is defined as all patients in the treated set who have baseline data and at least one on-treatment efficacy value.

Peak FEV1 0-3h response was defined as the difference between the maximum FEV1 measured within the first 3 hours post dosing after a treatment period of 24 weeks and the FEV1 baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Peak Forced Expiratory Volume in 1 Second (FEV1) Response Within 3 Hours Post Dosing (0-3h) After a Treatment Period of 24 Weeks.	0.315 Liter Standard Error 0.026	0.401 Liter Standard Error 0.025

PRIMARY outcome

Timeframe: Baseline and 24 weeks

Population: All patients from FAS.

The trough FEV1 is defined as the pre-dose FEV1 measured 10 minutes before the last administration of randomised treatment. Trough FEV1 response was defined as the difference between the trough FEV1 measured after a treatment period of 24 weeks and the FEV1 baseline measurement. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Trough FEV1 Response Determined After a Treatment Period of 24 Weeks.	0.056 Liter Standard Error 0.025	0.144 Liter Standard Error 0.024

PRIMARY outcome

Timeframe: 48 weeks

Population: All patients from FAS of the pooled twin studies 205.416 and 205.417. As \<50percent (149 of 454 patients in the placebo group and 122 of 453 patients in the Tio R5 group) of patients had severe exacerbation, the median time was not calculable.

Severe asthma exacerbations were pre-defined as all asthma exacerbations that required treatment with systemic (including oral) corticosteroids for at least 3 days or (in case of ongoing and pre-existing systemic corticosteroid therapy) that required at least a doubling of the previous daily dose of systemic corticosteroids for at least 3 days.

Outcome measures

Outcome measures
Measure	Placebo n=454 Participants Patients treated with matching placebo	Tio R5 n=453 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Time to First Severe Asthma Exacerbation During the 48-week Treatment of the Pooled Data From the Two Twin Trials 205.416 (NCT00772538) and the Present 205.417 (NCT00776984).	NA Days Inter-Quartile Range NA As \<50percent (149 of 454 patients in the placebo group) of patients had severe exacerbation, the median time was not calculable.	NA Days Inter-Quartile Range NA As \<50percent (122 of 453 patients in the Tio R5 group) of patients had severe exacerbation, the median time was not calculable.

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All patients from FAS.

Peak FVC 0-3h response was defined as the difference between the maximum FVC measured within the first 3 hours post dosing after a treatment period of 24 weeks and the FVC baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Peak (Within 3 Hours Post-dosing) Forced Vital Capacity (FVC) Response at the End of the 24-week Treatment Period.	0.355 Liter Standard Error 0.033	0.445 Liter Standard Error 0.032

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All patients from FAS.

The trough FVC is defined as the pre-dose FVC measured 10 minutes before the last administration of randomised treatment. Trough FVC response was defined as the difference between the trough FVC measured after a treatment period of 24 weeks and the FVC baseline measurement. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Trough FVC Response at the End of the 24-week Treatment Period.	0.022 Liter Standard Error 0.031	0.157 Liter Standard Error 0.031

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All patients from FAS.

The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FEV1 AUC0-3h after a treatment period of 24 weeks. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
FEV1 Area Under the Curve (AUC0-3h) Response at the End of the 24-week Treatment Period.	0.229 Liter Standard Error 0.024	0.315 Liter Standard Error 0.024

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All patients from FAS.

The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FVC AUC0-3h after a treatment period of 24 weeks. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
FVC (AUC0-3h) Response at the End of the 24-week Treatment Period.	0.230 Liter Standard Error 0.031	0.328 Liter Standard Error 0.030

SECONDARY outcome

Timeframe: Baseline and 48 weeks

Population: All patients from FAS.

Peak FEV1 0-3h response was defined as the difference between the maximum FEV1 measured within the first 3 hours post dosing after a treatment period of 48 weeks and the FEV1 baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Peak FEV1 0-3h Response at the End of the 48-week Treatment Period.	0.295 Liter Standard Error 0.026	0.367 Liter Standard Error 0.026

SECONDARY outcome

Timeframe: Baseline and 48 weeks

Population: All patients from FAS.

The trough FEV1 is defined as the pre-dose FEV1 measured 10 minutes before the last administration of randomised treatment. Trough FEV1 response was defined as the difference between the trough FEV1 measured after a treatment period of 48 weeks and the FEV1 baseline measurement. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Trough FEV1 Response at the End of the 48-week Treatment Period.	0.087 Liter Standard Error 0.025	0.129 Liter Standard Error 0.025

SECONDARY outcome

Timeframe: Baseline and 48 weeks

Population: All patients from FAS.

The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FEV1 AUC0-3h after a treatment period of 48 weeks. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
AUC0-3h FEV1 Response at the End of the 48-week Treatment Period.	0.217 Liter Standard Error 0.025	0.289 Liter Standard Error 0.024

SECONDARY outcome

Timeframe: Baseline and 48 weeks

Population: All patients from FAS.

Peak FVC 0-3h response was defined as the difference between the maximum FVC measured within the first 3 hours post dosing after a treatment period of 48 weeks and the FVC baseline measurement (10 minutes before the first dose of trial medication). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Peak FVC 0-3h Response at the End of the 48-week Treatment Period.	0.337 Liter Standard Error 0.033	0.462 Liter Standard Error 0.032

SECONDARY outcome

Timeframe: Baseline and 48 weeks

Population: All patients from FAS.

The trough FVC is defined as the pre-dose FVC measured 10 minutes before the last administration of randomised treatment. Trough FVC response was defined as the difference between the trough FVC measured after a treatment period of 48 weeks and the FVC baseline measurement. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Trough FVC Response at the End of the 48-week Treatment Period.	0.062 Liter Standard Error 0.032	0.173 Liter Standard Error 0.031

SECONDARY outcome

Timeframe: Baseline and 48 weeks

Population: All patients from FAS.

The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FVC AUC0-3h after a treatment period of 48 weeks. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
FVC AUC0-3h Response at the End of the 48-week Treatment Period.	0.223 Liter Standard Error 0.031	0.344 Liter Standard Error 0.030

SECONDARY outcome

Timeframe: Baseline and last 7 days before week 24 visit

Population: All patients from FAS.

Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Mean Pre-dose Morning Peak Expiratory Flow (PEFa.m.) Response (Diary Data) of Last-7-days-before-week-24-visit .	-6.996 L/min Standard Error 3.754	15.297 L/min Standard Error 3.602

SECONDARY outcome

Timeframe: Baseline and last 7 days before week 24 visit

Population: All patients from FAS.

Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Mean Pre-dose Evening Peak Expiratory Flow (PEFp.m.) Response (Diary Data) of Last-7-days-before-week 24-visit.	-3.865 L/min Standard Error 3.856	19.402 L/min Standard Error 3.670

SECONDARY outcome

Timeframe: Baseline and last 7 days before week 24 visit

Population: All patients from FAS.

Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Mean Pre-dose FEV1 a.m. Response (Diary Data) of Last-7-days-before-week 24-visit.	-0.055 Liter Standard Error 0.023	0.062 Liter Standard Error 0.022

SECONDARY outcome

Timeframe: Baseline and last 7 days before week 24 visit

Population: All patients from FAS.

Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Mean Pre-dose FEV1-p.m.Response (Diary Data) of Last-7-days-before-week 24-visit.	-0.050 Liter Standard Error 0.024	0.075 Liter Standard Error 0.023

SECONDARY outcome

Timeframe: Baseline and last 7 days before week 24 visit

Population: All patients from FAS.

Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). The PEF variability is the absolute difference between morning and evening PEF value divided by their mean, expressed as a percent. Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Mean PEF Variability Response (Absolute Difference Between Morning and Evening PEF Value Divided by Their Mean) of Last-7-days-before-week 24-visit.	-0.997 Percent Standard Error 0.602	-0.714 Percent Standard Error 0.578

SECONDARY outcome

Timeframe: 48 weeks

Population: All patients from FAS.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Number of Hospitalisations for Asthma Exacerbations Per Patient During the 48-week Treatment Period. 1 hospitalisations	9 Participants	6 Participants
Number of Hospitalisations for Asthma Exacerbations Per Patient During the 48-week Treatment Period. 0 hospitalisations	212 Participants	229 Participants
Number of Hospitalisations for Asthma Exacerbations Per Patient During the 48-week Treatment Period. 2+ hospitalisations	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 48 weeks

Population: All patients from FAS.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Number of Patients With at Least One Hospitalisation for Asthma Exacerbation During the 48-week Treatment Period.	10 Participants	8 Participants

SECONDARY outcome

Timeframe: 24 weeks

Population: All patients from FAS.

The AQLQ(S) total score was calculated as the mean of the responses to 32 questions for the domains Symptoms, Activity Limitations, Emotional Function and Environmental Stimuli and was analysed as an absolute value. The AQLQ(S) total score ranges from 1 (worst controlled) to 7 (best). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Quality of Life as Assessed by Standardised Asthma Quality of Life Questionnaire (AQLQ(S)) at the End of the 24-week Treatment Period.	5.084 Scores on a scale Standard Error 0.059	5.125 Scores on a scale Standard Error 0.057

SECONDARY outcome

Timeframe: 48 weeks

Population: All patients from FAS.

The AQLQ(S) total score was calculated as the mean of the responses to 32 questions for the domains Symptoms, Activity Limitations, Emotional Function and Environmental Stimuli and was analysed as an absolute value. The AQLQ(S) total score ranges from 1 (worst controlled) to 7 (best). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
AQLQ(S) Total Score at the End of the 48-week Treatment Period.	5.109 Scores on a scale Standard Error 0.060	5.147 Scores on a scale Standard Error 0.058

SECONDARY outcome

Timeframe: 24 weeks

Population: All patients from FAS.

For the ACQ, the total score was calculated as the mean of the responses to 7 questions and was analysed as an absolute value. The score ranges from 0 (no impairment) to 6 (maximum impairment). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Asthma Control as Assessed by Asthma Control Questionnaire (ACQ) at the End of the 24-week Treatment Period.	2.120 Scores on a scale Standard Error 0.053	1.995 Scores on a scale Standard Error 0.051

SECONDARY outcome

Timeframe: 48 weeks

Population: All patients from FAS.

For the ACQ, the total score was calculated as the mean of the responses to 7 questions and was analysed as an absolute value. The score ranges from 0 (no impairment) to 6 (maximum impairment). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
ACQ at the End of the 48-week Treatment Period.	2.107 Scores on a scale Standard Error 0.054	1.986 Scores on a scale Standard Error 0.052

SECONDARY outcome

Timeframe: Baseline and last 7 days before week 24 visit

Population: All patients from FAS.

Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). The response is defined as the change of the weekly mean from the baseline weekly mean. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Asthma Symptom Free Days Response During the Last-7-days-before-week-24-visit .	0.105 Days Standard Error 0.020	0.105 Days Standard Error 0.019

SECONDARY outcome

Timeframe: Baseline and last 7 days before week 24 visit

Population: All patients from FAS.

Weekly means obtained during the last 7 days before week 24 visit were compared. The response is defined as the change of the weekly mean from the baseline weekly mean. The use of PRN salbutamol (albuterol rescue medication) is determined by the number of puffs of rescue therapy used per day. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Patients treated with matching placebo	Tio R5 n=237 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Mean Pro Re Nata (as Needed, PRN) Rescue Medication Use Response During the Last-7-days-before-week-24-visit .	-0.714 Puffs Standard Error 0.140	-0.806 Puffs Standard Error 0.135

POST_HOC outcome

Timeframe: 24 weeks, 48 weeks

Population: FAS of combined data from the two twin trials 205.416 (NCT00772538) and 205.417 (NCT00776984)

The responder rate as assessed by the Asthma Control Questionnaire (ACQ) determined at 24-weeks and 48-weeks (on combined data from the two twin trials 205.416 (NCT00772538) and 205.417 (NCT00776984)). A patient was considered to be a responder if he or she was reported with an improvement (decrease) in the ACQ total score of at least 0.5 points. The ACQ total score was calculated as the mean of the responses to 7 questions and was analysed as an absolute value. The score ranges from 0 (no impairment) to 6 (maximum impairment). This outcome definition is taken from the primary outcome definition for the twin trials 205.418 (NCT01172808) and 205.419 (NCT01172821) of the same development program.

Outcome measures

Outcome measures
Measure	Placebo n=454 Participants Patients treated with matching placebo	Tio R5 n=453 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
The Responder Rate as Assessed by the ACQ From the Two Twin Trials 205.417 (NCT00776984) and the Present 205.416 (NCT00772538) 24 weeks	46.9 percentage of participants	53.9 percentage of participants
The Responder Rate as Assessed by the ACQ From the Two Twin Trials 205.417 (NCT00776984) and the Present 205.416 (NCT00772538) 48 weeks	45.2 percentage of participants	58.1 percentage of participants

Adverse Events

Placebo

Serious events: 15 serious events

Other events: 148 other events

Deaths: 0 deaths

Tio R5

Serious events: 18 serious events

Other events: 136 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=222 participants at risk Patients treated with matching placebo	Tio R5 n=237 participants at risk Patients treated with tiotropium inhalation solution 5 Î¼g qd
Cardiac disorders Arrhythmia supraventricular	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Cardiac disorders Atrial fibrillation	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Cardiac disorders Coronary artery occlusion	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Cardiac disorders Coronary artery stenosis	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Cardiac disorders Ventricular tachycardia	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Eye disorders Cataract	0.45% 1/222 • 48 weeks	0.00% 0/237 • 48 weeks
Gastrointestinal disorders Abdominal discomfort	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Gastrointestinal disorders Diverticulum	0.45% 1/222 • 48 weeks	0.00% 0/237 • 48 weeks
Gastrointestinal disorders Inguinal hernia	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Gastrointestinal disorders Small intestinal obstruction	0.45% 1/222 • 48 weeks	0.00% 0/237 • 48 weeks
General disorders Fat necrosis	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Infections and infestations Cellulitis	0.45% 1/222 • 48 weeks	0.00% 0/237 • 48 weeks
Infections and infestations Lobar pneumonia	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Infections and infestations Pneumonia	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Injury, poisoning and procedural complications Burns first degree	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Injury, poisoning and procedural complications Fall	0.45% 1/222 • 48 weeks	0.00% 0/237 • 48 weeks
Injury, poisoning and procedural complications Traumatic haematoma	0.45% 1/222 • 48 weeks	0.00% 0/237 • 48 weeks
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Musculoskeletal and connective tissue disorders Back disorder	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer stage unspecified	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Nervous system disorders Cerebrovascular accident	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Nervous system disorders Paraesthesia	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Respiratory, thoracic and mediastinal disorders Asthma	4.5% 10/222 • 48 weeks	3.8% 9/237 • 48 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks
Respiratory, thoracic and mediastinal disorders Sinus polyp	0.00% 0/222 • 48 weeks	0.42% 1/237 • 48 weeks

Other adverse events

Other adverse events
Measure	Placebo n=222 participants at risk Patients treated with matching placebo	Tio R5 n=237 participants at risk Patients treated with tiotropium inhalation solution 5 Î¼g qd
Infections and infestations Bronchitis	4.5% 10/222 • 48 weeks	5.1% 12/237 • 48 weeks
Infections and infestations Nasopharyngitis	9.0% 20/222 • 48 weeks	8.0% 19/237 • 48 weeks
Infections and infestations Upper respiratory tract infection	2.7% 6/222 • 48 weeks	5.5% 13/237 • 48 weeks
Investigations Peak expiratory flow rate decreased	26.1% 58/222 • 48 weeks	20.7% 49/237 • 48 weeks
Nervous system disorders Headache	5.9% 13/222 • 48 weeks	5.1% 12/237 • 48 weeks
Respiratory, thoracic and mediastinal disorders Asthma	44.6% 99/222 • 48 weeks	34.6% 82/237 • 48 weeks

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
Publication restrictions are in place

Restriction type: OTHER