Characterization of 24-hour Lung Function Profiles of Inh... | NCT01559116 | Trialant
NCT01559116
Sponsor
Boehringer Ingelheim
Status
Completed
Last Update Posted
Jul 16, 2015Estimated
Enrollment
219Actual
Phase
Phase 3
Conditions
Pulmonary Disease, Chronic Obstructive
Interventions
tiotropium + olodaterol
tiotropium
olodaterol
tiotropium
tiotropium + olodaterol
Placebo
Respimat
Countries
United States
Belgium
Canada
Denmark
Germany
Hungary
Netherlands
Protocol Section
Identification Module
NCT ID
NCT01559116
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
1237.20
Secondary IDs
ID
Type
Description
Link
2011-004710-42
EudraCT Number
EudraCT
Brief Title
Characterization of 24-hour Lung Function Profiles of Inhaled Tiotropium + Olodaterol Fixed Dose Combination in Patients Suffering From Chronic Obstructive Pulmonary Disease
Official Title
Randomised, Double-blind, Placebo-controlled, 6 Treatment, 4 Period, Incomplete Cross-over Trial to Characterise the 24-hour Lung Function Profiles of Tiotropium + Olodaterol Fixed Dose Combination (2.5/5 µg, 5/5 µg), Tiotropium (2.5 µg, 5 µg) and Olodaterol (5 µg) (Oral Inhalation, Delivered by the Respimat® Inhaler) After 6 Weeks Once Daily Treatment in Patients With Chronic Obstructive Pulmonary Disease (COPD) [VIVACITOTM]
Acronym
Not provided
Organization
Boehringer IngelheimINDUSTRY
Status Module
Record Verification Date
Jun 2015
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Mar 2012
Primary Completion Date
Aug 2013Actual
Completion Date
Aug 2013Actual
First Submitted Date
Mar 19, 2012
First Submission Date that Met QC Criteria
Mar 20, 2012
First Posted Date
Mar 21, 2012Estimated
Results Waived
Not provided
Results First Submitted Date
Jun 19, 2015
Results First Submitted that Met QC Criteria
Jun 19, 2015
Results First Posted Date
Jul 16, 2015Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Apr 3, 2014
Certification/Extension First Submitted that Passed QC Review
Apr 3, 2014
Certification/Extension First Posted Date
Apr 30, 2014Estimated
Last Update Submitted Date
Jun 19, 2015
Last Update Posted Date
Jul 16, 2015Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Boehringer IngelheimINDUSTRY
Collaborators
Not provided
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
The primary objective of the trial is to determine the 24-hour FEV1-time profile of tiotropium + olodaterol FDC, administered once daily by the RESPIMAT Inhaler after 6 weeks of treatment.
Detailed Description
Not provided
Conditions Module
Conditions
Pulmonary Disease, Chronic Obstructive
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
219Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
tiotropium+olodaterol FDC low dose
Experimental
tiotropium+olodaterol FDC low dose; 2 inhalations once daily (a.m. dosing)
Drug: tiotropium + olodaterol
Device: Respimat
tiotropium+olodaterol FDC high dose
Experimental
tiotropium+olodaterol FDC high dose; 2 inhalations once daily (a.m. dosing)
Drug: tiotropium + olodaterol
Device: Respimat
tiotropium low dose
Active Comparator
tiotropium low dose; 2 inhalations once daily (a.m. dosing)
Drug: tiotropium
Device: Respimat
tiotropium high dose
Active Comparator
tiotropium high dose; 2 inhalations once daily (a.m. dosing)
Drug: tiotropium
Device: Respimat
olodaterol
Active Comparator
one dose only; 2 inhalations once daily (a.m. dosing)
Drug: olodaterol
Device: Respimat
placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
tiotropium + olodaterol
Drug
low dose + one dose only
tiotropium+olodaterol FDC high dose
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Forced Expiratory Volume in 1 Second (FEV1) AUC0-24h Response [L] After 6 Weeks Treatment.
Area under the Forced Expiratory Volume in 1 second (FEV1) after 6 weeks treatement-time curve from 0 to 24 h post-dose, using the trapezoidal rule, divided by the duration (24 h) to report in litres.
Mean is actually the Adjusted mean.
The adjusted mean and standard error (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
day 1 and week 6
Secondary Outcomes
Measure
Description
Time Frame
FEV1 AUC0-12h Response [L] After 6 Weeks Treatment.
Area under the Forced Expiratory Volume in 1 second (FEV1) after 6 weeks treatement-time curve from 0 to 12 h post-dose, using the trapezoidal rule, divided by the duration (12h) to report in litres.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion criteria:
Diagnosis of chronic obstructive pulmonary disease
Relatively stable airway obstruction with a post-bronchodilator FEV1< 80% of predicted normal and a post-bronchodilator FEV1/FVC <70%
Male or female patients, 40 years of age or older
Smoking history of more than 10 pack years
Ability to perform technically acceptable pulmonary function tests and maintain records
Ability to inhale medication in a competent manner from the RESPIMAT Inhaler and from a metered dose inhaler (MDI)
Exclusion criteria:
significant disease other than COPD
clinically relevant abnormal lab values
history of asthma
diagnosis of thyrotoxicosis
diagnosis of paroxysmal tachycardia
history of myocardial infarction
unstable or life-threatening cardiac arrhythmia
Hospitalization for heart failure within the past year
known active tuberculosis
malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
history of life-threatening pulmonary obstruction
history of cystic fibrosis
clinically evident bronchiectasis
history of significant alcohol or drug abuse
history of thoracotomy with pulmonary resection
oral or patch ß-adrenergics
oral corticosteroid medication at unstable doses
regular use daytime oxygen therapy for more than one hour per day
Pulmonary rehabilitation program in the six weeks prior to the screening visit
Investigational drug within one month or six half lives (whichever is greater) prior to screening visit
Known hypersensitivity to ß-adrenergic drugs, BAC, EDTA
Pregnant or nursing women
Women of childbearing potential not using a highly effective method of birth control
Patients who have previously been randomised in this study or are currently participating in another study
Patients who are unable to comply with pulmonary medication restrictions prior to randomisation
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
40 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Boehringer Ingelheim
Boehringer Ingelheim
Study Chair
Locations
Facility
Status
City
State
ZIP
Country
Contacts
1237.20.1204 Boehringer Ingelheim Investigational Site
Jasper
Alabama
United States
1237.20.1203 Boehringer Ingelheim Investigational Site
Beeh KM, Westerman J, Kirsten AM, Hebert J, Gronke L, Hamilton A, Tetzlaff K, Derom E. The 24-h lung-function profile of once-daily tiotropium and olodaterol fixed-dose combination in chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2015 Jun;32:53-9. doi: 10.1016/j.pupt.2015.04.002. Epub 2015 May 6.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
This is a randomised, double-blind, placebo-controlled, 6 treatment, 4 period, incomplete cross-over design. Each patient was randomised to one of 30 treatment sequences. Each sequence consisted of four 6-week treatment periods separated by 3-week washout periods.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
All Subjects
Randomised, double-blind, placebo-controlled, 6 treatment, 4 period, incomplete cross-over trial to characterise the 24-hour lung function profiles of tiotropium + olodaterol fixed dose combination (2.5/5 μg, 5/5 μg), tiotropium (2.5 μg, 5 μg) and olodaterol (5 μg) (oral inhalation, delivered by the Respimat® Inhaler) after 6 weeks once daily treatment in patients with Chronic Obstructive Pulmonary Disease (COPD) [VIVACITOTM].
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Mexico
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
Not provided
Placebo Comparator
2 inhalations once daily (a.m. dosing)
Drug: Placebo
Device: Respimat
tiotropium
Drug
low dose
tiotropium low dose
olodaterol
Drug
one dose only
olodaterol
tiotropium
Drug
high dose
tiotropium high dose
tiotropium + olodaterol
Drug
low dose + one dose only
tiotropium+olodaterol FDC low dose
Placebo
Drug
placebo matching tiotropium+olodaterol FDC
placebo
Respimat
Device
Respimat inhaler
olodaterol
placebo
tiotropium high dose
tiotropium low dose
tiotropium+olodaterol FDC high dose
tiotropium+olodaterol FDC low dose
day 1 and week 6
FEV1 AUC12-24h Response [L] After 6 Weeks Treatment.
Area under the Forced Expiratory Volume in 1 second (FEV1) after 6 weeks treatement-time curve from 12 to 24 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
day 1 and week 6
Trough FEV1 Response [L] After 6 Weeks Treatment.
Trough Forced Expiratory Volume in 1 second (FEV1) response after 6 weeks treatment period.
The trough was defined as the mean of the 23 h and 23 h50 min measurements and Response was defined as the change from patient baseline.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
day 1 and week 6
Peak(0-3h) FEV1 Response [L] After 6 Weeks Treatment.
Peak (0-3h) Forced Expiratory Volume in 1 second (FEV1) response.
The peak was defined as the maximum value measured within the first 3 h post dosing and response was defined as the change from patient baseline.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
day 1 and week 6
FVC AUC0-24h Response [L] After 6 Weeks Treatment.
Area under the Forced Vital Capacity (FVC) after 6 weeks treatment period-time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
day 1 and week 6
FVC AUC0-12h Response [L] After 6 Weeks Treatment.
Area under the Forced Vital Capacity (FVC) after 6 weeks treatment period-time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
day 1 and week 6
FVC AUC12-24h Response [L] After 6 Weeks Treatment.
Area under the Forced Vital Capacity (FVC) after 6 weeks treatment period-time curve from 12 to 24 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
The trough was defined as the mean of the 23 h and 23 h50 min measurements and response was defined as the change from patient baseline.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
day1 and week 6
Peak (0-3h) FVC Response [L] After 6 Weeks Treatment.
Peak was defined as the maximum value measured within the first 3 h post dosing and response was defined as the change from patient baseline.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
day 1 and week 6
Easley
South Carolina
United States
1237.20.1201 Boehringer Ingelheim Investigational Site
Greenville
South Carolina
United States
1237.20.1202 Boehringer Ingelheim Investigational Site
Spartanburg
South Carolina
United States
1237.20.32203 Boehringer Ingelheim Investigational Site
Genk
Belgium
1237.20.32201 Boehringer Ingelheim Investigational Site
Ghent
Belgium
1237.20.32204 Boehringer Ingelheim Investigational Site
Jambes
Belgium
1237.20.02202 Boehringer Ingelheim Investigational Site
Québec
Quebec
Canada
1237.20.02201 Boehringer Ingelheim Investigational Site
Sherbrooke
Quebec
Canada
1237.20.45002 Boehringer Ingelheim Investigational Site
Hvidovre
Denmark
1237.20.45003 Boehringer Ingelheim Investigational Site
Odense C
Denmark
1237.20.45001 Boehringer Ingelheim Investigational Site
Silkeborg
Denmark
1237.20.49205 Boehringer Ingelheim Investigational Site
Berlin
Germany
1237.20.49204 Boehringer Ingelheim Investigational Site
Großhansdorf
Germany
1237.20.49203 Boehringer Ingelheim Investigational Site
Hamburg
Germany
1237.20.49206 Boehringer Ingelheim Investigational Site
Hamburg
Germany
1237.20.49201 Boehringer Ingelheim Investigational Site
Mannheim
Germany
1237.20.49207 Boehringer Ingelheim Investigational Site
Mönchengladbach
Germany
1237.20.49202 Boehringer Ingelheim Investigational Site
Wiesbaden
Germany
1237.20.36202 Boehringer Ingelheim Investigational Site
Gödöllö
Hungary
1237.20.36204 Boehringer Ingelheim Investigational Site
Komárom
Hungary
1237.20.36203 Boehringer Ingelheim Investigational Site
Pécs
Hungary
1237.20.36201 Boehringer Ingelheim Investigational Site
Szarvas
Hungary
1237.20.36205 Boehringer Ingelheim Investigational Site
Százhalombatta
Hungary
1237.20.31205 Boehringer Ingelheim Investigational Site
Almelo
Netherlands
1237.20.31202 Boehringer Ingelheim Investigational Site
Breda
Netherlands
1237.20.31201 Boehringer Ingelheim Investigational Site
Heerlen
Netherlands
1237.20.31204 Boehringer Ingelheim Investigational Site
Hengelo
Netherlands
1237.20.31203 Boehringer Ingelheim Investigational Site
Zutphen
Netherlands
FG000219 subjectsRandomised
COMPLETED
FG000193 subjectsCompleted all 4 treatment periods
NOT COMPLETED
FG00026 subjects
Type
Comment
Reasons
Adverse Event
FG00010 subjects
Lack of Efficacy
FG0001 subjects
Lost to Follow-up
FG0001 subjects
Protocol Violation
FG0001 subjects
Withdrawal by Subject
FG0004 subjects
other than stated above
FG0009 subjects
Treated Set (TS): This patient set includes all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
All Subjects
Randomised, double-blind, placebo-controlled, 6 treatment, 4 period, incomplete cross-over trial to characterise the 24-hour lung function profiles of tiotropium + olodaterol fixed dose combination (2.5/5 μg, 5/5 μg), tiotropium (2.5 μg, 5 μg) and olodaterol (5 μg) (oral inhalation, delivered by the Respimat® Inhaler) after 6 weeks once daily treatment in patients with Chronic Obstructive Pulmonary Disease (COPD) [VIVACITOTM].
Denominators
Units
Counts
Participants
BG000219
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
BG00061.1± 7.7
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00090
Male
BG000129
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
Forced Expiratory Volume in 1 Second (FEV1) AUC0-24h Response [L] After 6 Weeks Treatment.
Area under the Forced Expiratory Volume in 1 second (FEV1) after 6 weeks treatement-time curve from 0 to 24 h post-dose, using the trapezoidal rule, divided by the duration (24 h) to report in litres.
Mean is actually the Adjusted mean.
The adjusted mean and standard error (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
Full Analysis Set (FAS): This patient set included patients in the Treated Set (TS) who had any period baseline and any evaluable post-dose data for the primary efficacy endpoint at any Week 6 visits.
Posted
Mean
Standard Error
Litres (L)
day 1 and week 6
ID
Title
Description
OG000
Placebo
Placebo matching Tiotropium+Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT:2 Oral inhalations once daily in the morning for 6 weeks.
OG001
Olodaterol (5 µg)
Olodaterol solution for inhalation - RESPIMAT
2 oral inhalations once daily in the morning for 6 weeks.
OG002
Tiotropium (2.5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
OG003
Tiotropium (5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
OG004
Tiotropium+Olodaterol FDC (2.5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG005
Tiotropium+Olodaterol FDC (5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
Units
Counts
Participants
OG000132
OG001136
OG002136
OG003
Title
Denominators
Categories
Title
Measurements
OG000-0.037± 0.014
OG0010.129± 0.013
OG0020.117± 0.013
OG003
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
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.280
Standard Error of the Mean
0.014
2-Sided
95
0.252
0.309
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
Secondary
FEV1 AUC0-12h Response [L] After 6 Weeks Treatment.
Area under the Forced Expiratory Volume in 1 second (FEV1) after 6 weeks treatement-time curve from 0 to 12 h post-dose, using the trapezoidal rule, divided by the duration (12h) to report in litres.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
Full Analysis Set (FAS).
Posted
Mean
Standard Error
Litres (L)
day 1 and week 6
ID
Title
Description
OG000
Placebo
Placebo matching Tiotropium+Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 Oral inhalations once daily in the morning for 6 weeks.
OG001
Olodaterol (5 µg)
Olodaterol solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG002
Tiotropium (2.5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
Secondary
FEV1 AUC12-24h Response [L] After 6 Weeks Treatment.
Area under the Forced Expiratory Volume in 1 second (FEV1) after 6 weeks treatement-time curve from 12 to 24 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
Full Analysis Set (FAS).
Posted
Mean
Standard Error
Litres (L)
day 1 and week 6
ID
Title
Description
OG000
Placebo
Placebo matching Tiotropium+Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 Oral inhalations once daily in the morning for 6 weeks.
OG001
Olodaterol (5 µg)
Olodaterol solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG002
Tiotropium (2.5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
Secondary
Trough FEV1 Response [L] After 6 Weeks Treatment.
Trough Forced Expiratory Volume in 1 second (FEV1) response after 6 weeks treatment period.
The trough was defined as the mean of the 23 h and 23 h50 min measurements and Response was defined as the change from patient baseline.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
Full Analysis Set (FAS)
Posted
Mean
Standard Error
Litres
day 1 and week 6
ID
Title
Description
OG000
Placebo
Placebo matching Tiotropium+Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 Oral inhalations once daily in the morning for 6 weeks.)
OG001
Olodaterol (5 µg)
Olodaterol solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG002
Tiotropium (2.5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
Secondary
Peak(0-3h) FEV1 Response [L] After 6 Weeks Treatment.
Peak (0-3h) Forced Expiratory Volume in 1 second (FEV1) response.
The peak was defined as the maximum value measured within the first 3 h post dosing and response was defined as the change from patient baseline.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
Full Analysis Set (FAS).
Posted
Mean
Standard Error
Litres (L)
day 1 and week 6
ID
Title
Description
OG000
Placebo
Placebo matching Tiotropium+Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 Oral inhalations once daily in the morning for 6 weeks.
OG001
Olodaterol (5 µg)
Olodaterol solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG002
Tiotropium (2.5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
Secondary
FVC AUC0-24h Response [L] After 6 Weeks Treatment.
Area under the Forced Vital Capacity (FVC) after 6 weeks treatment period-time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
Full Analysis Set (FAS).
Posted
Mean
Standard Error
Litres(L)
day 1 and week 6
ID
Title
Description
OG000
Placebo
Placebo matching Tiotropium+Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 Oral inhalations once daily in the morning for 6 weeks.
OG001
Olodaterol (5 µg)
Olodaterol solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG002
Tiotropium (2.5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
Secondary
FVC AUC0-12h Response [L] After 6 Weeks Treatment.
Area under the Forced Vital Capacity (FVC) after 6 weeks treatment period-time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
Full Analysis Set (FAS)
Posted
Mean
Standard Error
Litres (L)
day 1 and week 6
ID
Title
Description
OG000
Placebo
Placebo matching Tiotropium+Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 Oral inhalations once daily in the morning for 6 weeks.
OG001
Olodaterol (5 µg)
Olodaterol solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG002
Tiotropium (2.5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
Secondary
FVC AUC12-24h Response [L] After 6 Weeks Treatment.
Area under the Forced Vital Capacity (FVC) after 6 weeks treatment period-time curve from 12 to 24 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
Full Analysis Set (FAS).
Posted
Mean
Standard Error
Litres (L)
day 1 and week 6
ID
Title
Description
OG000
Placebo
Placebo matching Tiotropium+Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 Oral inhalations once daily in the morning for 6 weeks.
OG001
Olodaterol (5 µg)
Olodaterol solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG002
Tiotropium (2.5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
The trough was defined as the mean of the 23 h and 23 h50 min measurements and response was defined as the change from patient baseline.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
Full Analysis Set (FAS).
Posted
Mean
Standard Error
Litres (L)
day1 and week 6
ID
Title
Description
OG000
Placebo
Placebo matching Tiotropium+Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 Oral inhalations once daily in the morning for 6 weeks.
OG001
Olodaterol (5 µg)
Olodaterol solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG002
Tiotropium (2.5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
Secondary
Peak (0-3h) FVC Response [L] After 6 Weeks Treatment.
Peak was defined as the maximum value measured within the first 3 h post dosing and response was defined as the change from patient baseline.
Mean is actually the Adjusted mean.
The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.
Full Analysis Set (FAS)
Posted
Mean
Standard Error
Litres (L)
day 1 and week 6
ID
Title
Description
OG000
Placebo
Placebo matching Tiotropium+Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 Oral inhalations once daily in the morning for 6 weeks.
OG001
Olodaterol (5 µg)
Olodaterol solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG002
Tiotropium (2.5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
Time Frame
From drug administration until 21 days after the last administration, upto 92 days.
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo
Placebo matching Tiotropium+Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 Oral inhalations once daily in the morning for 6 weeks.
4
138
40
138
EG001
Olodaterol (5 µg)
Olodaterol solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
8
138
21
138
EG002
Tiotropium (2.5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
5
137
30
137
EG003
Tiotropium (5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
3
138
29
138
EG004
Tiotropium+Olodaterol FDC (2.5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
4
136
23
136
EG005
Tiotropium+Olodaterol FDC (5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
1
139
25
139
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Atrial tachycardia
Cardiac disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0021 affected137 at risk
EG0030 affected138 at risk
EG0040 affected136 at risk
EG0050 affected139 at risk
Coronary artery disease
Cardiac disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0011 affected138 at risk
EG0021 affected137 at risk
EG003
Myocardial ischaemia
Cardiac disorders
MEDDRA 16.0
Systematic Assessment
EG0001 affected138 at risk
EG0010 affected138 at risk
EG0020 affected137 at risk
EG003
Impaired healing
General disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0011 affected138 at risk
EG0020 affected137 at risk
EG003
Inflammation
General disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0020 affected137 at risk
EG003
Anaphylactic reaction
Immune system disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0011 affected138 at risk
EG0020 affected137 at risk
EG003
Food allergy
Immune system disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0020 affected137 at risk
EG003
Hypersensitivity
Immune system disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0020 affected137 at risk
EG003
Pneumonia
Infections and infestations
MEDDRA 16.0
Systematic Assessment
EG0002 affected138 at risk
EG0010 affected138 at risk
EG0021 affected137 at risk
EG003
Salpingitis
Infections and infestations
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0020 affected137 at risk
EG003
Arthropod bite
Injury, poisoning and procedural complications
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0020 affected137 at risk
EG003
Comminuted fracture
Injury, poisoning and procedural complications
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0011 affected138 at risk
EG0020 affected137 at risk
EG003
Intervertebral disc protrusion
Musculoskeletal and connective tissue disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0011 affected138 at risk
EG0020 affected137 at risk
EG003
Lung neoplasm malignant
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0021 affected137 at risk
EG003
Rectal cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0020 affected137 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MEDDRA 16.0
Systematic Assessment
EG0001 affected138 at risk
EG0011 affected138 at risk
EG0020 affected137 at risk
EG003
Transient ischaemic attack
Nervous system disorders
MEDDRA 16.0
Systematic Assessment
EG0001 affected138 at risk
EG0010 affected138 at risk
EG0020 affected137 at risk
EG003
Renal infarct
Renal and urinary disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0011 affected138 at risk
EG0020 affected137 at risk
EG003
Ovarian cyst
Reproductive system and breast disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0020 affected137 at risk
EG003
Acute respiratory failure
Respiratory, thoracic and mediastinal disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0020 affected137 at risk
EG003
Chronic obstructive pulmonary disease
Respiratory, thoracic and mediastinal disorders
MEDDRA 16.0
Systematic Assessment
EG0002 affected138 at risk
EG0012 affected138 at risk
EG0020 affected137 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0011 affected138 at risk
EG0020 affected137 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0020 affected137 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0020 affected137 at risk
EG003
Dermatitis allergic
Skin and subcutaneous tissue disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0020 affected137 at risk
EG003
Arterial disorder
Vascular disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0011 affected138 at risk
EG0020 affected137 at risk
EG003
Arterial occlusive disease
Vascular disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0012 affected138 at risk
EG0020 affected137 at risk
EG003
Peripheral artery aneurysm
Vascular disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0011 affected138 at risk
EG0020 affected137 at risk
EG003
Peripheral artery thrombosis
Vascular disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0021 affected137 at risk
EG003
Peripheral vascular disorder
Vascular disorders
MEDDRA 16.0
Systematic Assessment
EG0000 affected138 at risk
EG0010 affected138 at risk
EG0021 affected137 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Nasopharyngitis
Infections and infestations
MEDDRA 16.0
Systematic Assessment
EG00014 affected138 at risk
EG00112 affected138 at risk
EG00212 affected137 at risk
EG00312 affected138 at risk
EG00412 affected136 at risk
EG0059 affected139 at risk
Chronic obstructive pulmonary disease
Respiratory, thoracic and mediastinal disorders
MEDDRA 16.0
Systematic Assessment
EG00015 affected138 at risk
EG0015 affected138 at risk
EG00213 affected137 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MEDDRA 16.0
Systematic Assessment
EG0007 affected138 at risk
EG0012 affected138 at risk
EG0023 affected137 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MEDDRA 16.0
Systematic Assessment
EG0009 affected138 at risk
EG0013 affected138 at risk
EG0024 affected137 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Point of Contact
Title
Organization
Phone
Extension
Email
Boehringer Ingelheim Call Center
Boehringer Ingelheim
1-800-243-0127
clintriage.rdg@boehringer-ingelheim.com
ID
Term
D029424
Pulmonary Disease, Chronic Obstructive
Ancestor Terms
ID
Term
D008173
Lung Diseases, Obstructive
D008171
Lung Diseases
D012140
Respiratory Tract Diseases
D002908
Chronic Disease
D020969
Disease Attributes
D010335
Pathologic Processes
D013568
Pathological Conditions, Signs and Symptoms
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C000611386
tiotropium-olodaterol
D000069447
Tiotropium Bromide
C549647
olodaterol
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
Browse Leaves
Not provided
Browse Branches
Not provided
135
OG004135
OG005138
0.133
± 0.014
OG0040.241± 0.014
OG0050.244± 0.013
OG001
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.115
Standard Error of the Mean
0.014
2-Sided
95
0.087
0.143
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG003
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.110
Standard Error of the Mean
0.014
2-Sided
95
0.082
0.139
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG000
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.277
Standard Error of the Mean
0.015
2-Sided
95
0.249
0.306
Adjusted mean difference to placebo is calculated.
No
Superiority or Other
OG001
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Median Difference (Final Values)
0.111
Standard Error of the Mean
0.014
2-Sided
95
0.083
0.140
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG002
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.124
Standard Error of the Mean
0.014
2-Sided
95
0.096
0.152
Adjusted mean difference to Tiotropium low dose (2.5 µg) is calculated.
No
Superiority or Other
OG003
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Median Difference (Final Values)
0.107
Standard Error of the Mean
0.014
2-Sided
95
0.079
0.136
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG003
Tiotropium (5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
OG004
Tiotropium+Olodaterol FDC (2.5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG005
Tiotropium+Olodaterol FDC (5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
Units
Counts
Participants
OG000132
OG001136
OG002136
OG003135
OG004135
OG005138
Title
Denominators
Categories
Title
Measurements
OG000-0.013± 0.015
OG0010.179± 0.015
OG0020.171± 0.015
OG0030.186± 0.015
OG0040.310± 0.015
OG0050.305± 0.015
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
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.319
Standard Error of the Mean
0.015
95
0.289
0.349
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.126
Standard Error of the Mean
0.015
2-Sided
95
0.096
0.156
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG003
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.119
Standard Error of the Mean
0.015
2-Sided
95
0.089
0.149
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG000
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.323
Standard Error of the Mean
0.015
2-Sided
95
0.293
0.354
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.131
Standard Error of the Mean
0.015
2-Sided
95
0.101
0.161
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG002
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.139
Standard Error of the Mean
0.015
2-Sided
95
0.109
0.169
Adjusted mean difference to Tiotropium low dose (2.5 µg) is calculated.
No
Superiority or Other
OG003
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.124
Standard Error of the Mean
0.015
2-Sided
95
0.093
0.154
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG003
Tiotropium (5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
OG004
Tiotropium+Olodaterol FDC (2.5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG005
Tiotropium+Olodaterol FDC (5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
Units
Counts
Participants
OG000132
OG001136
OG002136
OG003135
OG004135
OG005138
Title
Denominators
Categories
Title
Measurements
OG000-0.060± 0.014
OG0010.079± 0.013
OG0020.062± 0.013
OG0030.081± 0.014
OG0040.172± 0.014
OG0050.182± 0.013
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
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.243
Standard Error of the Mean
0.015
2-Sided
95
0.212
0.273
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Median Difference (Final Values)
0.103
Standard Error of the Mean
0.015
2-Sided
95
0.074
0.133
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG003
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Median Difference (Final Values)
0.102
Standard Error of the Mean
0.015
2-Sided
95
0.072
0.132
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG000
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.232
Standard Error of the Mean
0.015
2-Sided
95
0.201
0.262
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.093
Standard Error of the Mean
0.015
2-Sided
95
0.063
0.123
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG002
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.110
Standard Error of the Mean
0.015
2-Sided
95
0.080
0.140
Adjusted mean difference to Tiotropium low dose (2.5 µg) is calculated.
No
Superiority or Other
OG003
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.091
Standard Error of the Mean
0.015
2-Sided
95
0.061
0.121
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG003
Tiotropium (5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
OG004
Tiotropium+Olodaterol FDC (2.5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG005
Tiotropium+Olodaterol FDC (5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
Units
Counts
Participants
OG000132
OG001136
OG002136
OG003135
OG004135
OG005138
Title
Denominators
Categories
Title
Measurements
OG000-0.006± 0.015
OG0010.109± 0.015
OG0020.095± 0.015
OG0030.122± 0.015
OG0040.196± 0.015
OG0050.201± 0.015
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
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.207
Standard Error of the Mean
0.017
2-Sided
95
0.173
0.241
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.092
Standard Error of the Mean
0.017
2-Sided
95
0.059
0.126
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG003
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.079
Standard Error of the Mean
0.017
2-Sided
95
0.045
0.113
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG000
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.201
Standard Error of the Mean
0.017
2-Sided
95
0.167
0.235
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.086
Standard Error of the Mean
0.017
2-Sided
95
0.052
0.120
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG002
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.101
Standard Error of the Mean
0.017
2-Sided
95
0.067
0.135
Adjusted mean difference to Tiotropium low dose (2.5 µg) is calculated.
No
Superiority or Other
OG003
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.073
Standard Error of the Mean
0.017
2-Sided
95
0.039
0.107
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG003
Tiotropium (5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
OG004
Tiotropium+Olodaterol FDC (2.5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG005
Tiotropium+Olodaterol FDC (5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
Units
Counts
Participants
OG000135
OG001138
OG002136
OG003137
OG004135
OG005138
Title
Denominators
Categories
Title
Measurements
OG0000.072± 0.017
OG0010.291± 0.016
OG0020.290± 0.016
OG0030.300± 0.016
OG0040.422± 0.016
OG0050.411± 0.016
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
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.338
Standard Error of the Mean
0.017
2-Sided
95
0.305
0.371
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.120
Standard Error of the Mean
0.017
2-Sided
95
0.087
0.153
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG003
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.111
Standard Error of the Mean
0.017
2-Sided
95
0.078
0.143
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG000
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.350
Standard Error of the Mean
0.017
2-Sided
95
0.317
0.383
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.131
Standard Error of the Mean
0.017
2-Sided
95
0.098
0.164
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG002
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.132
Standard Error of the Mean
0.017
2-Sided
95
0.099
0.165
Adjusted mean difference to Tiotropium low dose (2.5 µg) is calculated.
No
Superiority or Other
OG003
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.122
Standard Error of the Mean
0.017
2-Sided
95
0.089
0.155
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG003
Tiotropium (5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
OG004
Tiotropium+Olodaterol FDC (2.5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG005
Tiotropium+Olodaterol FDC (5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
Units
Counts
Participants
OG000132
OG001136
OG002136
OG003135
OG004135
OG005138
Title
Denominators
Categories
Title
Measurements
OG000-0.065± 0.023
OG0010.158± 0.022
OG0020.172± 0.022
OG0030.191± 0.022
OG0040.331± 0.022
OG0050.368± 0.022
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
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.433
Standard Error of the Mean
0.022
2-Sided
95
0.389
0.477
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.210
Standard Error of the Mean
0.022
2-Sided
95
0.166
0.253
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG003
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.177
Standard Error of the Mean
0.022
2-Sided
95
0.133
0.221
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG000
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.396
Standard Error of the Mean
0.023
2-Sided
95
0.352
0.441
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.173
Standard Error of the Mean
0.022
2-Sided
95
0.129
0.217
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG002
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.159
Standard Error of the Mean
0.022
2-Sided
95
0.115
0.203
Adjusted mean difference to Tiotropium low dose (2.5 µg) is calculated. is calculated.
No
Superiority or Other
OG003
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.140
Standard Error of the Mean
0.022
2-Sided
95
0.096
0.184
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG003
Tiotropium (5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
OG004
Tiotropium+Olodaterol FDC (2.5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG005
Tiotropium+Olodaterol FDC (5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
Units
Counts
Participants
OG000132
OG001136
OG002136
OG003135
OG004135
OG005138
Title
Denominators
Categories
Title
Measurements
OG000-0.023± 0.024
OG0010.240± 0.024
OG0020.249± 0.024
OG0030.261± 0.024
OG0040.420± 0.024
OG0050.440± 0.024
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
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.463
Standard Error of the Mean
0.024
2-Sided
95
0.417
0.509
Adjusted mean difference to placebo is calculated.
No
Superiority or Other
OG001
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.200
Standard Error of the Mean
0.023
2-Sided
95
0.154
0.246
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG003
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.179
Standard Error of the Mean
0.023
2-Sided
95
0.133
0.225
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG000
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.443
Standard Error of the Mean
0.024
2-Sided
95
0.396
0.490
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.181
Standard Error of the Mean
0.024
2-Sided
95
0.134
0.227
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG002
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.171
Standard Error of the Mean
0.024
2-Sided
95
0.125
0.218
Adjusted mean difference to Tiotropium low dose (2.5 µg) is calculated.
No
Superiority or Other
OG003
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.159
Standard Error of the Mean
0.024
2-Sided
95
0.113
0.206
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG003
Tiotropium (5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
OG004
Tiotropium+Olodaterol FDC (2.5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG005
Tiotropium+Olodaterol FDC (5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
Units
Counts
Participants
OG000132
OG001136
OG002136
OG003135
OG004135
OG005138
Title
Denominators
Categories
Title
Measurements
OG000-0.108± 0.023
OG0010.077± 0.023
OG0020.095± 0.023
OG0030.122± 0.023
OG0040.243± 0.023
OG0050.296± 0.023
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
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.404
Standard Error of the Mean
0.025
2-Sided
95
0.355
0.453
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.219
Standard Error of the Mean
0.025
2-Sided
95
0.170
0.267
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG003
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.174
Standard Error of the Mean
0.025
2-Sided
95
0.126
0.223
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG000
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.351
Standard Error of the Mean
0.025
2-Sided
95
0.301
0.400
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.166
Standard Error of the Mean
0.025
2-Sided
95
0.117
0.214
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG002
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.148
Standard Error of the Mean
0.025
2-Sided
95
0.099
0.197
Adjusted mean difference to Tiotropium low dose (2.5 µg) is calculated.
No
Superiority or Other
OG003
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.121
Standard Error of the Mean
0.025
2-Sided
95
0.072
0.170
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG003
Tiotropium (5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
OG004
Tiotropium+Olodaterol FDC (2.5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG005
Tiotropium+Olodaterol FDC (5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
Units
Counts
Participants
OG000132
OG001136
OG002136
OG003135
OG004135
OG005138
Title
Denominators
Categories
Title
Measurements
OG000-0.025± 0.026
OG0010.134± 0.026
OG0020.115± 0.026
OG0030.183± 0.026
OG0040.282± 0.026
OG0050.304± 0.026
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.329
Standard Error of the Mean
0.028
2-Sided
95
0.274
0.385
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.170
Standard Error of the Mean
0.028
2-Sided
95
0.115
0.225
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG003
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.121
Standard Error of the Mean
0.028
2-Sided
95
0.066
0.176
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG000
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Median Difference (Final Values)
0.307
Standard Error of the Mean
0.029
2-Sided
95
0.251
0.363
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.147
Standard Error of the Mean
0.028
2-Sided
95
0.092
0.203
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG002
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.166
Standard Error of the Mean
0.028
2-Sided
95
0.111
0.222
Adjusted mean difference to Tiotropium low dose (2.5 µg) is calculated.
No
Superiority or Other
OG003
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.099
Standard Error of the Mean
0.028
2-Sided
95
0.043
0.154
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG003
Tiotropium (5 µg)
Tiotropium solution for inhalation - RESPIMAT : 2 oral inhalations once daily in the morning for 6 weeks.
OG004
Tiotropium+Olodaterol FDC (2.5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
OG005
Tiotropium+Olodaterol FDC (5/5 µg)
Tiotropium + Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 oral inhalations once daily in the morning for 6 weeks.
Units
Counts
Participants
OG000132
OG001136
OG002136
OG003135
OG004135
OG005138
Title
Denominators
Categories
Title
Measurements
OG0000.159± 0.029
OG0010.463± 0.029
OG0020.450± 0.029
OG0030.470± 0.029
OG0040.612± 0.029
OG0050.621± 0.028
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
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.462
Standard Error of the Mean
0.028
2-Sided
95
0.408
0.516
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.159
Standard Error of the Mean
0.027
2-Sided
95
0.105
0.212
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG003
OG005
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.151
Standard Error of the Mean
0.027
2-Sided
95
0.098
0.205
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.
No
Superiority or Other
OG000
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.452
Standard Error of the Mean
0.028
2-Sided
95
0.398
0.507
Adjusted mean difference to Placebo is calculated.
No
Superiority or Other
OG001
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.149
Standard Error of the Mean
0.028
2-Sided
95
0.095
0.203
Adjusted mean difference to Olodaterol (5 µg) is calculated.
No
Superiority or Other
OG002
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.161
Standard Error of the Mean
0.028
2-Sided
95
0.107
0.216
Adjusted mean difference to Tiotropium low dose (2.5 µg) is calculated.
No
Superiority or Other
OG003
OG004
Mixed Models Analysis
Mixed effect model repeated measures (MMRM) with fixed effects for treatment,period and random effect for patient.
<0.0001
Mean Difference (Final Values)
0.142
Standard Error of the Mean
0.028
2-Sided
95
0.087
0.196
Adjusted mean difference to Tiotropium high dose (5 µg) is calculated.