Safety and Efficacy of 12-wk Treatment With Two Doses of... | NCT00737100

ID	Type	Description	Link
2008-001156-43	EudraCT Number	EudraCT

Safety and Efficacy of 12-wk Treatment With Two Doses of... | NCT00737100 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Tiotropium Respimat 2.5 mcg	Experimental	patient to receive low dose tiotropium once daily	Drug: tiotropium bromide-low dose-2.5mcg
Tiotropium Respimat 5 mcg	Experimental	patient to receive high dose tiotropium once daily	Drug: Tiotropium bromide 5 mcg
Placebo Respimat	Placebo Comparator	patient to receive placebo once daily	Drug: Placebo Respimat

Name	Type	Description	Arm Group Labels	Other Names
Placebo Respimat	Drug	patient to receive placebo matching active drug once daily	Placebo Respimat

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Predicted FEV1 AUC0-4 Response at the End of Week 12	Outcome measure description: Change from baseline in percent predicted Forced Expiratory Volume in one second (FEV1) Area Under the Curve from 0 to 4 hours (AUC0-4). Calculated as percent predicted at week 12 minus percent predicted at baseline.	Baseline, Week 12
Percent Predicted FEV1 Trough Response at the End of Week 12	Outcome measure description: Change from baseline in percent predicted trough Forced Expiratory Volume in one second. Calculated as percent predicted at week 12 minus percent predicted at baseline.	Baseline, Week 12

Secondary Outcomes

Measure	Description	Time Frame
Percent Predicted FVC AUC0-4 Response at the End of Week 12	Change from baseline in percent predicted Forced Vital Capacity (FVC) Area Under the Curve from 0 to 4 hours (AUC0-4). Calculated as percent predicted at week 12 minus percent predicted at baseline.	Baseline, Week 12
Percent Predicted FVC Trough Response at the End of Week 12

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
205.339.006 Boehringer Ingelheim Investigational Site		Tucson	Arizona		United States
205.339.019 Boehringer Ingelheim Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25819269	Derived	Ratjen F, Koker P, Geller DE, Langellier-Cocteaux B, Le Maulf F, Kattenbeck S, Moroni-Zentgraf P, Elborn JS; Tiotropium Cystic Fibrosis Study Group. Tiotropium Respimat in cystic fibrosis: Phase 3 and Pooled phase 2/3 randomized trials. J Cyst Fibros. 2015 Sep;14(5):608-14. doi: 10.1016/j.jcf.2015.03.004. Epub 2015 Mar 26.
25188297

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Patients randomised to receive matching placebo
FG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Adverse Event		FG0006 subjects FG0015 subjects FG0023 subjects
Lost to Follow-up		FG0000 subjects FG0011 subjects FG0020 subjects
Withdrawal by Subject		FG0000 subjects FG0010 subjects FG0023 subjects
Reason discontinued not explained above		FG0001 subjects FG0011 subjects FG0021 subjects

Arm/Group Information

ID	Title	Description
BG000	Placebo	Patients randomised to receive matching placebo
BG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
BG002	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00020.4± 11.6 BG00121.5± 12.0 BG00220.7± 11.3 BG003

Age, Customized

Number

years

Title

Denominators

Categories

<= 11 years

Title	Measurements
	BG00044 BG00142 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00072 BG00181 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Asian

Title	Measurements
	BG0000 BG0011 BG002

Height

Mean

Standard Deviation

centimeters

Title

Denominators

Categories

Title	Measurements
	BG000157.4± 17.2 BG001157.7± 17.0 BG002

Weight

Mean

Standard Deviation

kilograms

Title

Denominators

Categories

Title	Measurements
	BG00052.1± 19.0 BG00151.0± 17.3 BG002

Body Mass Index

Mean

Standard Deviation

kilogram/square meter

Title

Denominators

Categories

Title	Measurements
	BG00020.3± 4.4 BG00119.9± 4.0 BG002

Alcohol history

Number

Participants

Title

Denominators

Categories

Drinks no alcohol

Title	Measurements
	BG000130 BG001112 BG002

Smoking history

Number

Participants

Title

Denominators

Categories

Never smoked

Title	Measurements
	BG000159 BG001157 BG002

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

Percent Predicted FEV1 AUC0-4 Response at the End of Week 12

Outcome measure description: Change from baseline in percent predicted Forced Expiratory Volume in one second (FEV1) Area Under the Curve from 0 to 4 hours (AUC0-4). Calculated as percent predicted at week 12 minus percent predicted at baseline.

Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement

Posted

Least Squares Mean

Standard Error

Percentage change

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Patients randomised to receive matching placebo
OG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG002	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts
Participants	OG000163 OG001158 OG002169

Title

Denominators

Categories

Title	Measurements
	OG000-1.74± 0.65 OG0011.20± 0.66 OG0021.65± 0.63

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	Comparison of Tiotropium 2.5 microgram dose versus placebo	Mixed Models Analysis	Adjusted for baseline, center, visit and age group	0.001	Comment for p-value: Hierarchical testing was applied. Comparison of 2.5 dose to be performed only if superiority of tiotropium 5.0 dose compared to placebo was shown for both primary endpoints.	Mean Difference (Final Values)	2.94				95	1.19	4.70				No	Superiority or Other

Primary

Percent Predicted FEV1 Trough Response at the End of Week 12

Outcome measure description: Change from baseline in percent predicted trough Forced Expiratory Volume in one second. Calculated as percent predicted at week 12 minus percent predicted at baseline.

Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement

Posted

Least Squares Mean

Standard Error

Percentage change

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Patients randomised to receive matching placebo
OG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG002	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts
Participants

Secondary

Percent Predicted FVC AUC0-4 Response at the End of Week 12

Change from baseline in percent predicted Forced Vital Capacity (FVC) Area Under the Curve from 0 to 4 hours (AUC0-4). Calculated as percent predicted at week 12 minus percent predicted at baseline.

Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement

Posted

Least Squares Mean

Standard Error

Percentage change

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Patients randomised to receive matching placebo
OG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG002	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts
Participants

Secondary

Percent Predicted FVC Trough Response at the End of Week 12

Change from baseline in percent predicted trough Forced Vital Capacity (FVC). Calculated as percent predicted at week 12 minus percent predicted at baseline.

Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement

Posted

Least Squares Mean

Standard Error

Percentage change

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Patients randomised to receive matching placebo
OG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG002	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts
Participants

Secondary

Pre-bronchodilator FEF25-75 Percent Predicted at the End of Week 12

Forced Expiratory Flow at 25-75% of vital capacity (FEF25-75). Calculated as percent predicted at week 12 minus percent predicted at baseline.

Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement

Posted

Least Squares Mean

Standard Error

Percentage change

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Patients randomised to receive matching placebo
OG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG002	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts
Participants

Secondary

Change From Baseline in Residual Volume/Total Lung Capacity (RV/TLC) at the End of Week 12

Change from baseline in static lung hyperinflation as measured by RV/TLC. Calculated as percent predicted at week 12 minus percent predicted at baseline.

Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement

Posted

Least Squares Mean

Standard Error

Percentage change

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Patients randomised to receive matching placebo
OG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG002	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts
Participants

Secondary

Respiratory and Systemic Symptoms Questionnaire (RSSQ)

Outcome measure description: The RSSQ questionnaire is used to determine the presence or absence of an exacerbation during the recall period.

Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement

Posted

Number

Participants

12 weeks

ID	Title	Description
OG000	Placebo	Patients randomised to receive matching placebo
OG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG002	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts
Participants

Secondary

Change From Baseline in CFQ Scores - Adult Group

The Cystic Fibrosis questionnaire (CFQ) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adults with CF. This validation questionnaire consists of 50 items on generic and disease-specific scales. The scores range from 0 to 100, with higher scores indicating better health.

Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement

Posted

Mean

Standard Deviation

units on a scale

12 weeks

ID	Title	Description
OG000	Placebo	Patients randomised to receive matching placebo
OG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG002	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts

Secondary

Change From Baseline in CFQ Scores - Adolescents Group

The Cystic Fibrosis questionnaire (CFQ) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents (age 6-13) with CF. This validation questionnaire consists of 50 items on generic and disease-specific scales. The scores range from 0 to 100, with higher scores indicating better health.

Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement

Posted

Mean

Standard Deviation

units on a scale

12 weeks

ID	Title	Description
OG000	Placebo	Patients randomised to receive matching placebo
OG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG002	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts

Secondary

Change From Baseline in CFQ Scores - Parent Questionnaire

The Cystic Fibrosis questionnaire (CFQ) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents with CF - parent questionnaire. This validation questionnaire consists of 50 items on generic and disease-specific scales. The scores range from 0 to 100, with higher scores indicating better health.

Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement

Posted

Mean

Standard Deviation

units on a scale

12 weeks

ID	Title	Description
OG000	Placebo	Patients randomised to receive matching placebo
OG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG002	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts

Secondary

Amount of Tiotropium Eliminated in Urine From 0 to 4 Hours at Steady State (Ae0-4,ss)

Ae0-4,ss represents the amount of tiotropium that is eliminated in urine from time 0 to 4 hours at steady state

Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement - patients >= 12 years

Posted

Geometric Mean

Geometric Coefficient of Variation

pre-dose, and 5 minutes (min), 20 min, 1 hour (h), and 2 h post-dose

ID	Title	Description
OG000	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG001	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts
Participants	OG000

Secondary

Maximum Measured Concentration at Steady State (Cmax,ss)

Cmax,ss represents the maximum measured concentration of tiotropium in plasma at steady state.

Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement - patients >= 12 years

Posted

Geometric Mean

Geometric Coefficient of Variation

pg/mL

pre-dose, and 5 minutes (min), 20 min, 1 hour (h), and 2 h post-dose

ID	Title	Description
OG000	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG001	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts
Participants	OG000

Secondary

Time From Dosing to the Maximum Concentration (Tmax,ss)

Tmax,ss represents the time from dosing to the maximum concentration of tiotropium in plasma

Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement - patients >= 12 years

Posted

Median

Full Range

pre-dose, and 5 minutes (min), 20 min, 1 hour (h), and 2 h post-dose

ID	Title	Description
OG000	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG001	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts
Participants	OG000

Secondary

Clinical Relevant Abnormalities for Vital Signs and Laboratory Evaluation

Clinical Relevant Abnormalities for Vital Signs and Laboratory evaluation. Any new or clinically relevant worsening of baseline conditions was reported as Adverse Event.

Treated set

Posted

Number

participants

From first drug administration until 30 days after last drug administration (up to 121 days)

ID	Title	Description
OG000	Placebo	Patients randomised to receive matching placebo
OG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
OG002	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Patients randomised to receive matching placebo	21	168	87	168
EG001	Tiotropium Respimat 2.5 Micrograms	Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily	28	166	95	166
EG002	Tiotropium Respimat 5 Micrograms	Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily	21	176	110	176

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Aplastic anaemia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk
Cystic fibrosis	Congenital, familial and genetic disorders	MedDRA 13.0	Systematic Assessment	EG0005 affected168 at risk EG0018 affected166 at risk EG0028 affected176 at risk
Cystic fibrosis lung	Congenital, familial and genetic disorders	MedDRA 13.0	Systematic Assessment	EG0007 affected168 at risk EG0014 affected166 at risk EG0024 affected176 at risk
Constipation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0021 affected176 at risk
Distal intestinal obstruction syndrome	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0021 affected176 at risk
Gastritis	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Gastrointestinal obstruction	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0010 affected166 at risk EG0021 affected176 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0010 affected166 at risk EG0021 affected176 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0021 affected176 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Application site hypersensitivity	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Infusion related reaction	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Multi-organ failure	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Bronchitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0002 affected168 at risk EG0012 affected166 at risk EG0020 affected176 at risk
Bronchopneumonia	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0011 affected166 at risk EG0021 affected176 at risk
Cellulitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk
Chronic sinusitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk
Lung infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Lung infection pseudomonal	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0011 affected166 at risk EG0021 affected176 at risk
Oral herpes	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Overgrowth bacterial	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk
Pleurisy viral	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Pneumonia	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Pseudomonas infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0021 affected176 at risk
Respiratory tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk
Sepsis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk
Stenotrophomonas infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Pulmonary function test decreased	Investigations	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk
Hyperlipasaemia	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0010 affected166 at risk EG0021 affected176 at risk
Suicide attempt	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Renal disorder	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0021 affected176 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0010 affected166 at risk EG0023 affected176 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0012 affected166 at risk EG0020 affected176 at risk
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected168 at risk EG0011 affected166 at risk EG0020 affected176 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk
Antibiotic prophylaxis	Surgical and medical procedures	MedDRA 13.0	Systematic Assessment	EG0001 affected168 at risk EG0010 affected166 at risk EG0020 affected176 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cystic fibrosis	Congenital, familial and genetic disorders	MedDRA 13.0	Systematic Assessment	EG00012 affected168 at risk EG00115 affected166 at risk EG00217 affected176 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00010 affected168 at risk EG00113 affected166 at risk EG0029 affected176 at risk
Pyrexia	General disorders	MedDRA 13.0	Systematic Assessment	EG00017 affected168 at risk EG0019 affected166 at risk EG00218 affected176 at risk
Bronchitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0007 affected168 at risk EG0014 affected166 at risk EG00210 affected176 at risk
Nasopharyngitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG00014 affected168 at risk EG00111 affected166 at risk EG00214 affected176 at risk
Sinusitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0006 affected168 at risk EG0013 affected166 at risk EG0029 affected176 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0006 affected168 at risk EG0018 affected166 at risk EG00211 affected176 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0009 affected168 at risk EG0015 affected166 at risk EG0024 affected176 at risk
Headache	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG00018 affected168 at risk EG0017 affected166 at risk EG00214 affected176 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG00034 affected168 at risk EG00134 affected166 at risk EG00246 affected176 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0009 affected168 at risk EG0018 affected166 at risk EG0026 affected176 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0007 affected168 at risk EG00112 affected166 at risk EG00211 affected176 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0004 affected168 at risk EG0019 affected166 at risk EG00210 affected176 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG00013 affected168 at risk EG0015 affected166 at risk EG00211 affected176 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0009 affected168 at risk EG0016 affected166 at risk EG0029 affected176 at risk
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0008 affected168 at risk EG00111 affected166 at risk EG00213 affected176 at risk

Ancestor Terms

ID	Term
D010182	Pancreatic Diseases
D004066	Digestive System Diseases
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232	Infant, Newborn, Diseases

Ancestor Terms

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

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	Comparison of Tiotropium 2.5 microgram dose versus placebo	Mixed Models Analysis	Adjusted for baseline, center, visit and age group	0.0184	Comment for p-value: Hierarchical testing was applied. Comparison of 2.5 dose to be performed only if superiority of tiotropium 5.0 dose compared to placebo was shown for both primary endpoints.	Mean Difference (Final Values)	2.24				95	0.38	4.11				No	Superiority or Other
OG000 OG002	Comparison of Tiotropium 5.0 microgram dose versus placebo	Mixed Models Analysis	Adjusted for baseline, center, visit and age group	0.0179	Comment for p-value: Hierarchical testing was applied. Comparison of 2.5 dose to be performed only if superiority of tiotropium 5.0 dose compared to placebo was shown for both primary endpoints.	Mean Difference (Final Values)	2.22				95	0.38	4.06				No	Superiority or Other

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	Comparison of Tiotropium 2.5 microgram dose versus placebo	Mixed Models Analysis	Adjusted for baseline, center, visit and age group	0.0756		Mean Difference (Final Values)	1.83				95	-0.19	3.86				No	Superiority or Other
OG000 OG002	Comparison of Tiotropium 5.0 microgram dose versus placebo	Mixed Models Analysis	Adjusted for baseline, center, visit and age group	0.0023		Mean Difference (Final Values)	3.12				95	1.12	5.12				No	Superiority or Other

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	Comparison of Tiotropium 2.5 microgram dose versus placebo	Mixed Models Analysis	Adjusted for baseline, center, visit and age group	0.3857		Mean Difference (Final Values)	0.85				95	-1.08	2.79				No	Superiority or Other
OG000 OG002	Comparison of Tiotropium 5.0 microgram dose versus placebo	Mixed Models Analysis	Adjusted for baseline, center, visit and age group	0.2199		Mean Difference (Final Values)	1.19				95	-0.72	3.11				No	Superiority or Other

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	Comparison of Tiotropium 2.5 microgram dose versus placebo	Mixed Models Analysis	Adjusted for baseline, center, visit and age group	0.0363		Mean Difference (Final Values)	4.19				95	0.27	8.11				No	Superiority or Other
OG000 OG002	Comparison of Tiotropium 5.0 microgram dose versus placebo	Mixed Models Analysis	Adjusted for baseline, center, visit and age group	0.0073		Mean Difference (Final Values)	5.34				95	1.45	9.23				No	Superiority or Other

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	Comparison of Tiotropium 2.5 microgram dose versus placebo	Mixed Models Analysis	Adjusted for baseline, center, visit and age group	0.7414		Mean Difference (Final Values)	0.01				95	-0.06	0.08				No	Superiority or Other
OG000 OG002	Comparison of Tiotropium 5.0 microgram dose versus placebo	Mixed Models Analysis	Adjusted for baseline, center, visit and age group	0.1418		Mean Difference (Final Values)	0.05				95	-0.02	0.12				No	Superiority or Other

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	Comparison of Tiotropium 2.5 microgram dose versus placebo	Regression, Logistic	Covariates of treatment and age group	0.8515		Odds Ratio (OR)	0.79				95	0.37	1.72				No	Superiority or Other
OG000 OG002	Comparison of Tiotropium 5.0 microgram dose versus placebo	Regression, Logistic	Adjusted for baseline, center, visit and age group	0.5565		Odds Ratio (OR)	0.72				95	0.33	1.59				No	Superiority or Other

Title

Denominators

Categories

Physical (N=99, 102, 105)

Title	Measurements
	OG000-2.5± 14.8 OG001-0.0± 14.1 OG002-2.9± 11.4

Role (N=94, 100, 103)

Title	Measurements
	OG0000.7± 12.0 OG001-2.7± 12.0 OG002-2.1± 15.1

Vitality (N=99, 101, 105)

Title	Measurements
	OG000-2.3± 15.0 OG001-1.8± 16.4 OG002-3.3± 17.7

Emotion (N=99, 101, 105)

Title	Measurements
	OG000-1.1± 11.5 OG001-1.3± 13.5 OG0020.1± 12.1

Social (N=99, 101, 106)

Title	Measurements
	OG000-1.1± 12.3 OG001-1.0± 10.7 OG002-0.8± 11.1

Body (N=99,101, 106)

Title	Measurements
	OG0000.4± 18.4 OG001-0.9± 15.3 OG0021.7± 16.4

Eat (N=99,101,106)

Title	Measurements
	OG0001.5± 9.5 OG0010.2± 10.3 OG0020.0± 16.4

Treat (N=99, 101, 106)

Title	Measurements
	OG0000.9± 15.5 OG001-1.4± 14.1 OG002-1.7± 12.7

Health (N=99, 101, 106)

Title	Measurements
	OG000-1.9± 15.1 OG001-3.2± 18.3 OG002-0.6± 18.1

Weight (N=95, 101, 103)

Title	Measurements
	OG0001.4± 22.2 OG001-3.3± 28.9 OG002-0.0± 26.0

Respirat (N=93, 101, 103)

Title	Measurements
	OG000-1.3± 14.8 OG001-3.7± 15.8 OG002-1.8± 14.3

Digest (N=93, 101, 103)

Title	Measurements
	OG0000.8± 14.9 OG001-1.3± 13.7 OG0020.3± 14.9

Title

Denominators

Categories

Physical (N=46, 42, 54)

Title	Measurements
	OG0001.1± 18.0 OG0013.2± 14.8 OG002-1.9± 15.0

School (N=46, 42, 55)

Title	Measurements
	OG0001.1± 14.3 OG001-1.6± 10.9 OG002-1.1± 13.5

Body (N=46, 42, 55)

Title	Measurements
	OG0002.8± 13.9 OG001-0.3± 16.1 OG002-0.1± 15.7

School (N=46, 42, 55)

Title	Measurements
	OG0001.2± 18.8 OG0014.2± 19.2 OG0022.4± 20.9

Eat (N=46, 42, 55)

Title	Measurements
	OG000-1.4± 19.7 OG001-2.4± 17.3 OG0021.6± 22.8

Treat (N=46, 42, 55)

Title	Measurements
	OG0000.2± 16.5 OG001-1.9± 20.1 OG0025.7± 19.5

Respirat (N=46, 42, 55)

Title	Measurements
	OG000-1.4± 15.2 OG0011.2± 16.7 OG002-3.0± 20.2

Digest (N=46, 42, 55)

Title	Measurements
	OG000-5.1± 26.3 OG0012.4± 26.9 OG002-3.0± 35.3

Title

Denominators

Categories

Physical (N=46, 45, 53)

Title	Measurements
	OG000-0.1± 15.4 OG0014.9± 15.9 OG0020.2± 12.7

Emotion (N=46, 45, 52)

Title	Measurements
	OG000-0.3± 11.2 OG0010.0± 16.0 OG002-0.1± 15.7

Vitality (N=46, 44, 53)

Title	Measurements
	OG000-0.1± 12.3 OG0013.3± 13.1 OG002-1.5± 14.9

School (N=46, 45, 52)

Title	Measurements
	OG000-4.8± 19.5 OG0012.2± 26.3 OG0020.4± 17.0

Eat (N=46, 43, 49)

Title	Measurements
	OG000-2.2± 23.7 OG001-0.8± 21.2 OG0023.4± 15.9

Body (N=46, 45, 52)

Title	Measurements
	OG000-3.9± 18.6 OG001-1.7± 21.7 OG002-3.2± 22.6

Treat (N=46, 45, 52)

Title	Measurements
	OG000-2.4± 18.6 OG0012.5± 16.4 OG002-0.2± 21.4

Health (N=46, 45, 52)

Title	Measurements
	OG000-2.7± 21.4 OG0013.5± 23.1 OG002-3.0± 20.7

Respirat (N=45, 43, 50)

Title	Measurements
	OG000-2.8± 16.4 OG001-2.2± 18.8 OG002-6.0± 14.2

Digest (N=46, 43, 50)

Title	Measurements
	OG000-0.7± 15.6 OG001-1.8± 17.0 OG0021.1± 16.8

Weight (N=45, 45, 49)

Title	Measurements
	OG000-5.2± 35.5 OG0011.5± 30.1 OG0024.1± 31.6

Title

Denominators

Categories

Blood chloride decreased

Title	Measurements
	OG0000 OG0010 OG0021

Blood glucose increased

Title	Measurements
	OG0001 OG0011 OG0020

Blood pressure increased

Title	Measurements
	OG0002 OG0011 OG0020

Blood sodium decreased

Title	Measurements
	OG0000 OG0010 OG0021

Eosinophil count increased

Title	Measurements
	OG0000 OG0011 OG0020

Hepatic enzyme increased

Title	Measurements
	OG0002 OG0010 OG0020

Oxygen saturation decreased

Title	Measurements
	OG0000 OG0010 OG0021

Vitamin K decreased

Title	Measurements
	OG0001 OG0010 OG0020

White blood cell count increased

Title	Measurements
	OG0000 OG0011 OG0020