Study to Evaluate the Effect on Lung Function and ECG Whe... | NCT02030535

ID	Type	Description	Link
2013-002652-32	EudraCT Number	EudraCT

Label	Type	Description	Intervention Names
Tiotropium/Olodaterol FDC	Experimental	patient will receive tiotropium and olodaterol in a fixed dose combination	Drug: tiotropium Drug: olodaterol
Tiotropium and Olodaterol FC	Experimental	patient will receive tiotropium and olodaterol in a free combination	Drug: olodaterol Drug: tiotropium
Placebo	Placebo Comparator	patient will receive placebo	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
olodaterol	Drug	free combination with tiotropium	Tiotropium and Olodaterol FC

Measure	Description	Time Frame
Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3hours) Response After Single-dose Administration	The response was defined as the change from patient baseline. Patient baseline was the average of the mean pre-dose values (period baseline) on each test day (Visit 2 (Day 1), Visit 3 (Day 22 (±7days)), and Visit 4 (Day 43±7days)). For patients who did not complete all periods, patient baseline was the average of the available period baselines. The means presented are the adjusted means.	1 hour (h) and 10 min pre-dose and at 15 min, 30 min, 1 h, 2 h and 3 h post-dose

Measure	Description	Time Frame
Mean (Heart Rate Corrected QT Interval (Using Fredericia Adjustment)) QTcF Interval Change From Patient Baseline Over All Post-dose Time Points	Mean QTcF interval change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1237.7.49004 Boehringer Ingelheim Investigational Site		Berlin			Germany
1237.7.49005 Boehringer Ingelheim Investigational Site

ID	Title	Description
FG000	Overall Study	Total number of patients randomised and treated in the study. (This is a cross-over trial consisting of a minimum two-week screening period. After screening, eligible patients were randomly assigned to one of 12 treatment sequences. Each patient received all three treatments as single doses on the three test days. Between test days with single dose administration there are 3-week washout periods.)

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

Secondary

Mean (Heart Rate Corrected QT Interval (Using Fredericia Adjustment)) QTcF Interval Change From Patient Baseline Over All Post-dose Time Points

Mean QTcF interval change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Units	Counts
Participants	OG00052 OG00152 OG00252

Title

Denominators

Categories

Title	Measurements
	OG0001.3± 7.1 OG0012.2± 6.9 OG0021.9± 6.9

Secondary

Peak QTcF Interval Change From Patient Baseline Over All Post-dose Time Points

Peak QTcF interval change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

Mean Heart Rate Change From Patient Baseline Over All Post-dose Time Points

Mean heart rate change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

bpm

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

Peak Heart Rate Change From Patient Baseline Over All Post-dose Time Points

Peak heart rate change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

bpm

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations (a.m. dosing) via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations (a.m. dosing) via RESPIMAT® inhaler

Primary

Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3hours) Response After Single-dose Administration

The response was defined as the change from patient baseline. Patient baseline was the average of the mean pre-dose values (period baseline) on each test day (Visit 2 (Day 1), Visit 3 (Day 22 (±7days)), and Visit 4 (Day 43±7days)).

For patients who did not complete all periods, patient baseline was the average of the available period baselines.

The means presented are the adjusted means.

Full Analysis Set (FAS): This patient set included all patients in the TS who had at least 1 visit (Visit 2(Day1), Visit 3(Day22), or Visit 4(Day43)) with both the period baseline value plus any evaluable post-dose spirometry measurement from the same visit.

Posted

Mean

Standard Error

Litres

1 hour (h) and 10 min pre-dose and at 15 min, 30 min, 1 h, 2 h and 3 h post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations ante meridiem (a.m.) dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler.
OG002	Tiotropium 5μg + Olodaterol 5μg

Secondary

Heart Rate Change From Patient Baseline at Individual Post-dose Time Points

Heart rate change from patient baseline at individual post-dose time points

Treated set (observed cases)

Posted

Mean

Standard Deviation

bpm

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

Mean RR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Mean RR change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

Peak RR Change From Patient Baseline Over All Post-dose Time Points

Peak RR change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

RR Change From Patient Baseline at Individual Post-dose Time Points

RR change from patient baseline at individual post-dose time points

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

Mean QT (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Mean QT change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

Peak QT (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Peak QT change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

QT Change From Patient Baseline at Individual Post-dose Time Points

QT change from patient baseline at individual post-dose time points

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

Mean QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment)) Change From Patient Baseline Over All Post-dose Time Points

Mean QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment))change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

Peak QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment)) Change From Patient Baseline Over All Post-dose Time Points

Peak QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment))change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

QTcB Change From Patient Baseline at Individual Post-dose Time Points

QTcB change from patient baseline at individual post-dose time points

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

Mean PR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Mean PR change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

Peak PR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Peak PR change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

PR Change From Patient Baseline at Individual Post-dose Time Points

PR change from patient baseline at individual post-dose time points

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

Mean QRS (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Mean QRS change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

Peak QRS (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Peak QRS change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Secondary

QRS Change From Patient Baseline at Individual Post-dose Time Points

QRS change from patient baseline at individual post-dose time points

Treated set (observed cases)

Posted

Mean

Standard Deviation

40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

ID	Title	Description
OG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.
OG001	Tio+Olo 5/5μg	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation. 2 inhalations a.m. dosing via RESPIMAT® inhaler
OG002	Tiotropium 5μg + Olodaterol 5μg	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination (FC) (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing via RESPIMAT® inhaler

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Prinzmetal angina	Cardiac disorders	MEDDRA 17.0	Systematic Assessment		EG0000 affected53 at risk EG0010 affected52 at risk EG0021 affected52 at risk
Cystocele	Reproductive system and breast disorders	MEDDRA 17.0	Systematic Assessment		EG0000 affected53 at risk EG0010 affected52 at risk EG0021 affected52 at risk

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

ID	Term
C549647	olodaterol
D000069447	Tiotropium Bromide

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

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Single test dose of oral inhalation of Placebo via RESPIMAT inhaler. 2 inhalations a.m. dosing.	0	53	3	53
EG001	Tio+Olo FDC	Single test dose of oral inhalation of Tio+Olo FDC(fixed dose combination) (5/5 μg) inhalation solution as fixed dose inhalation solution (Tio+Olo FDC) 2.5 μg each per actuation via RESPIMAT inhaler. 2 inhalations a.m. dosing.	0	52	1	52
EG002	Tiotropium and Olodaterol FC	Single test dose of oral inhalation of tiotropium (5 μg) and olodaterol (5 μg) free combination FC (Tio/Olo free combination) Olodaterol: 5 μg (2.5 μg per actuation) Tiotropium: 5 μg (2.5 μg per actuation) 2 inhalations a.m. dosing.	2	52	2	52