Trial Outcomes & Findings for To Evaluate the Effect of Inhaled Medication Together With Exercise and Activity Training on Exercise Capacity and Daily Activities in Patients With Chronic Lung Disease With Obstruction of Airways (NCT NCT02085161)

NCT ID: NCT02085161

Last Updated: 2017-01-06

Results Overview

Endurance time during ESWT to symptom limitation at walking speed corresponding to 85% of predicted maximum oxygen consumption (VO2 peak) after 8 weeks of pharmacological treatment and non-pharmacological intervention. The numerical value of endurance time in seconds was transformed in log10 scale to correct for skewness and then an analysis of covariance (ANCOVA) was fitted to the log10-transformed data and the least square means (LSMean) and standard error (SE) were obtained. To present the results in a way easier for interpretation, the least square mean from the ANCOVA fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate to obtain the geometric mean and the corresponding SE was transformed using delta method to get the corresponding SE of the geometric mean.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 304 participants
• Primary outcome timeframe: Week 8
• Results posted on: 2017-01-06

Participant Flow

An exploratory, randomised, partially double-blinded, placebo-controlled, parallel group trial to explore the effects of tiotropium + olodaterol fixed dose combination (FDC) or tiotropium, supervised exercise training and behaviour modification on exercise capacity and physical activity in patients with Chronic Obstructive Pulmonary Disease (COPD)

Participant milestones

Measure	Placebo With Behavioural Modification (BM) Placebo matching tiotropium + olodaterol FDC or tiotropium solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium (Tio) 5 Micro-grams (μg) With BM Tiotropium 5 μg solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks; ET was conducted for 8 weeks.
Overall Study STARTED	76	76	76	76
Overall Study COMPLETED	64	66	71	66
Overall Study NOT COMPLETED	12	10	5	10

Reasons for withdrawal

Measure	Placebo With Behavioural Modification (BM) Placebo matching tiotropium + olodaterol FDC or tiotropium solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium (Tio) 5 Micro-grams (μg) With BM Tiotropium 5 μg solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks; ET was conducted for 8 weeks.
Overall Study Not Treated	1	0	0	0
Overall Study Adverse Event	8	5	4	5
Overall Study Protocol Violation	0	1	0	1
Overall Study Withdrawal by Subject	2	4	0	3
Overall Study Other Reason	1	0	1	1

Baseline Characteristics

To Evaluate the Effect of Inhaled Medication Together With Exercise and Activity Training on Exercise Capacity and Daily Activities in Patients With Chronic Lung Disease With Obstruction of Airways

Baseline characteristics by cohort

Measure	Placebo With Behavioural Modification (BM) n=75 Participants Placebo matching tiotropium + olodaterol FDC or tiotropium solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium (Tio) 5 Micro-grams (μg) With BM n=76 Participants Tiotropium 5 μg solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM n=76 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM n=76 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks; ET was conducted for 8 weeks.	Total n=303 Participants Total of all reporting groups
Age, Continuous	64.4 Years STANDARD_DEVIATION 6.6 • n=5 Participants	65.1 Years STANDARD_DEVIATION 6.4 • n=7 Participants	65.0 Years STANDARD_DEVIATION 6.9 • n=5 Participants	64.7 Years STANDARD_DEVIATION 6.5 • n=4 Participants	64.8 Years STANDARD_DEVIATION 6.6 • n=21 Participants
Gender Female	23 Participants n=5 Participants	21 Participants n=7 Participants	28 Participants n=5 Participants	31 Participants n=4 Participants	103 Participants n=21 Participants
Gender Male	52 Participants n=5 Participants	55 Participants n=7 Participants	48 Participants n=5 Participants	45 Participants n=4 Participants	200 Participants n=21 Participants

PRIMARY outcome

Timeframe: Week 8

Population: Full analysis set (FAS): This patient set included all patients in the Treated set (TS) who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint. Patients were assigned to the FAS after implementation of any data handling rules that set measurements to missing. Patients with available data were included.

Endurance time during ESWT to symptom limitation at walking speed corresponding to 85% of predicted maximum oxygen consumption (VO2 peak) after 8 weeks of pharmacological treatment and non-pharmacological intervention. The numerical value of endurance time in seconds was transformed in log10 scale to correct for skewness and then an analysis of covariance (ANCOVA) was fitted to the log10-transformed data and the least square means (LSMean) and standard error (SE) were obtained. To present the results in a way easier for interpretation, the least square mean from the ANCOVA fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate to obtain the geometric mean and the corresponding SE was transformed using delta method to get the corresponding SE of the geometric mean.

Outcome measures

Measure	Placebo With Behavioural Modification (BM) n=65 Participants Placebo matching tiotropium + olodaterol FDC or tiotropium solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium (Tio) 5 Micro-grams (μg) With BM n=67 Participants Tiotropium 5 μg solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM n=72 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM n=70 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks; ET was conducted for 8 weeks.
Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 8 Weeks	244.07 Second Standard Error 17.666	254.18 Second Standard Error 18.099	315.32 Second Standard Error 21.671	355.73 Second Standard Error 24.787

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set (FAS): This patient set included all patients in the TS who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint. Patients were assigned to the FAS after implementation of any data handling rules that set measurements to missing. Patients with available data were included.

Average daily walking time measured by the activity monitor in the week prior to Week 12.

Outcome measures

Measure	Placebo With Behavioural Modification (BM) n=55 Participants Placebo matching tiotropium + olodaterol FDC or tiotropium solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium (Tio) 5 Micro-grams (μg) With BM n=57 Participants Tiotropium 5 μg solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM n=60 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM n=57 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks; ET was conducted for 8 weeks.
Average Daily Walking Time Measured by the Activity Monitor in the Week Prior to Week 12	4670.78 Second Standard Error 211.798	4145.85 Second Standard Error 207.351	4831.85 Second Standard Error 202.261	4338.80 Second Standard Error 207.252

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set (FAS): This patient set included all patients in the TS who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint. Patients were assigned to the FAS after implementation of any data handling rules that set measurements to missing. Patients with available data were included.

Average daily walking intensity measured by the activity monitor in the week prior to 12 weeks of treatment. The Movement Intensity (MI) is derived from the acceleration signals. Since seismic sensors measure gravitational acceleration (g) in static situations, the acceleration signal is expressed relative to g (1g = 9.81m/s2). To calculate movement intensity (MI) the gravitational acceleration in static situations was removed and the rotation vector of the three accelerometer signals was calculated. The MI gives an indication of the power of movements.

Outcome measures

Measure	Placebo With Behavioural Modification (BM) n=54 Participants Placebo matching tiotropium + olodaterol FDC or tiotropium solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium (Tio) 5 Micro-grams (μg) With BM n=56 Participants Tiotropium 5 μg solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM n=58 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM n=57 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks; ET was conducted for 8 weeks.
Average Daily Walking Intensity Measured by the Activity Monitor in the Week Prior to 12 Weeks of Treatment	0.20 Multiple of 9.8*(meters / (second^2)) Standard Error 0.003	0.20 Multiple of 9.8*(meters / (second^2)) Standard Error 0.003	0.20 Multiple of 9.8*(meters / (second^2)) Standard Error 0.003	0.20 Multiple of 9.8*(meters / (second^2)) Standard Error 0.003

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set (FAS): This patient set included all patients in the TS who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint. Patients were assigned to the FAS after implementation of any data handling rules that set measurements to missing. Patients with available data were included.

Perceived difficulties as evaluated with FPI-SF. FPI-SF self-report questionnaire has 6 domains: Body care(5 items), Household maintenance(8 items), Physical exercise(5 items), Recreation(5 items), Spiritual activities(4 items) and Social interaction(5 items) with five possible answers on each item: Do with no difficulty - 3, Do with some difficulty - 2, Do with great difficulty - 1, don't do because of health reasons - 0, and don't do because choose not to - 0. Domain scores are expressed as mean values, with at least 6 non-missing items required for the household maintenance domain and at least 3 non-missing items for the other domains. Total score is the mean across the six domains. So total and domain scores range from 0 to 3, with higher scores indicating higher levels of functional activity within and across domains. Respondents engaged in many activities with no difficulty will score high on the FPI, while those who perform few activities with much difficulty will score low.

Outcome measures

Measure	Placebo With Behavioural Modification (BM) n=64 Participants Placebo matching tiotropium + olodaterol FDC or tiotropium solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium (Tio) 5 Micro-grams (μg) With BM n=65 Participants Tiotropium 5 μg solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM n=71 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM n=67 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks; ET was conducted for 8 weeks.
Perceived Difficulties as Evaluated With Functional Performance Inventory-Short Form (FPI-SF) Total Score at Week 12	2.191 Units on a scale Standard Error 0.040	2.207 Units on a scale Standard Error 0.040	2.335 Units on a scale Standard Error 0.038	2.268 Units on a scale Standard Error 0.039

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set (FAS): This patient set included all patients in the TS who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint. Patients were assigned to the FAS after implementation of any data handling rules that set measurements to missing. Patients with available data were included.

Endurance time during ESWT to symptom limitation at walking speed corresponding to 85% of maximum oxygen consumption (VO2 peak) after 12 weeks of pharmacological treatment and non-pharmacological intervention. The numerical value of endurance time in seconds was transformed in log10 scale to correct for skewness and then the ANCOVA was fitted to the log10-transformed data and the least square means and SE were obtained. To present the results in a way easier for interpretation, the least square mean from the ANCOVA fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate to obtain the geometric mean and the corresponding SE was transformed using delta method to get the corresponding SE of the geometric mean.

Outcome measures

Measure	Placebo With Behavioural Modification (BM) n=62 Participants Placebo matching tiotropium + olodaterol FDC or tiotropium solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium (Tio) 5 Micro-grams (μg) With BM n=64 Participants Tiotropium 5 μg solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM n=71 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM n=66 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks; ET was conducted for 8 weeks.
Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 12 Weeks	243.30 Second Standard Error 18.680	255.67 Second Standard Error 19.292	302.61 Second Standard Error 21.691	324.21 Second Standard Error 24.095

SECONDARY outcome

Timeframe: Week 8

Population: Full analysis set (FAS): This patient set included all patients in the TS who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint. Patients were assigned to the FAS after implementation of any data handling rules that set measurements to missing. Patients with available data were included.

One hour, Post-dose Forced Expiratory Volume in One Second (FEV1) after 8 weeks of treatment.

Outcome measures

Measure	Placebo With Behavioural Modification (BM) n=65 Participants Placebo matching tiotropium + olodaterol FDC or tiotropium solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium (Tio) 5 Micro-grams (μg) With BM n=67 Participants Tiotropium 5 μg solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM n=72 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM n=70 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks; ET was conducted for 8 weeks.
One Hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 8 Weeks of Treatment	1.375 Liter Standard Error 0.027	1.550 Liter Standard Error 0.027	1.731 Liter Standard Error 0.026	1.705 Liter Standard Error 0.026

SECONDARY outcome

Timeframe: Week 8

Population: Full analysis set (FAS): This patient set included all patients in the TS who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint. Patients were assigned to the FAS after implementation of any data handling rules that set measurements to missing. Patients with available data were included.

One hour, Post-dose Forced Vital Capacity (FVC) after 8 weeks of treatment.

Outcome measures

Measure	Placebo With Behavioural Modification (BM) n=65 Participants Placebo matching tiotropium + olodaterol FDC or tiotropium solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium (Tio) 5 Micro-grams (μg) With BM n=67 Participants Tiotropium 5 μg solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM n=72 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM n=70 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks; ET was conducted for 8 weeks.
One Hour, Post-dose Forced Vital Capacity (FVC) After 8 Weeks of Treatment	2.974 Liter Standard Error 0.047	3.259 Liter Standard Error 0.046	3.504 Liter Standard Error 0.044	3.452 Liter Standard Error 0.045

SECONDARY outcome

Timeframe: Week 8

Population: Full analysis set (FAS): This patient set included all patients in the TS who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint. Patients were assigned to the FAS after implementation of any data handling rules that set measurements to missing. Patients with available data were included.

Resting inspiratory capacity (IC) measured at 1.5 hours post dose after 8 weeks of treatment.

Outcome measures

Measure	Placebo With Behavioural Modification (BM) n=64 Participants Placebo matching tiotropium + olodaterol FDC or tiotropium solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium (Tio) 5 Micro-grams (μg) With BM n=66 Participants Tiotropium 5 μg solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM n=72 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM n=68 Participants Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks; ET was conducted for 8 weeks.
Resting Inspiratory Capacity (IC) Measured at 1.5 Hours Post Dose After 8 Weeks of Treatment	2.452 Liter Standard Error 0.051	2.627 Liter Standard Error 0.050	2.755 Liter Standard Error 0.048	2.771 Liter Standard Error 0.049

Adverse Events

Placebo With Behavioural Modification (BM)

Serious events: 4 serious events

Other events: 22 other events

Deaths: 0 deaths

Tiotropium (Tio) 5 Micro-grams (μg) With BM

Serious events: 11 serious events

Other events: 19 other events

Deaths: 0 deaths

Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM

Serious events: 3 serious events

Other events: 16 other events

Deaths: 0 deaths

Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM

Serious events: 8 serious events

Other events: 19 other events

Deaths: 0 deaths

Total

Serious events: 26 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo With Behavioural Modification (BM) n=75 participants at risk Placebo matching tiotropium + olodaterol FDC or tiotropium solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium (Tio) 5 Micro-grams (μg) With BM n=76 participants at risk Tiotropium 5 μg solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM n=76 participants at risk Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM n=76 participants at risk Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks; ET was conducted for 8 weeks.	Total n=303 participants at risk Total
Cardiac disorders Acute myocardial infarction	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Cardiac disorders Angina pectoris	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Cardiac disorders Atrial fibrillation	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Cardiac disorders Coronary artery disease	1.3% 1/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Hepatobiliary disorders Cholelithiasis	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Hepatobiliary disorders Hepatotoxicity	1.3% 1/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Infections and infestations Abdominal abscess	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Infections and infestations Pneumonia	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Infections and infestations Urinary tract infection	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Injury, poisoning and procedural complications Alcohol poisoning	1.3% 1/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Musculoskeletal and connective tissue disorders Compartment syndrome	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant genitourinary tract neoplasm	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma unspecified histology indolent stage IV	1.3% 1/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic neoplasm	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer metastatic	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.66% 2/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Nervous system disorders Carotid artery stenosis	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Nervous system disorders Syncope	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Reproductive system and breast disorders Prostatitis	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.3% 1/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	2.6% 2/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.7% 5/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.66% 2/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Respiratory, thoracic and mediastinal disorders Pulmonary hilum mass	1.3% 1/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Vascular disorders Aortic aneurysm	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Vascular disorders Aortic stenosis	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.00% 0/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	0.33% 1/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.

Other adverse events

Measure	Placebo With Behavioural Modification (BM) n=75 participants at risk Placebo matching tiotropium + olodaterol FDC or tiotropium solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium (Tio) 5 Micro-grams (μg) With BM n=76 participants at risk Tiotropium 5 μg solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM n=76 participants at risk Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks.	Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM n=76 participants at risk Tiotropium 5 μg plus olodaterol 5 μg FDC solution was delivered to the patients orally once daily via RESPIMAT inhaler, with BM for 12 weeks; ET was conducted for 8 weeks.	Total n=303 participants at risk Total
Infections and infestations Nasopharyngitis	10.7% 8/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	11.8% 9/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	5.3% 4/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	13.2% 10/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	10.2% 31/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Musculoskeletal and connective tissue disorders Back pain	5.3% 4/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	2.6% 2/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	1.3% 1/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	2.6% 8/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	21.3% 16/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	13.2% 10/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	15.8% 12/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	17.1% 13/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	16.8% 51/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.7% 2/75 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	7.9% 6/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	2.6% 2/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	2.6% 2/76 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.	4.0% 12/303 • From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days. All adverse events, serious and non-serious, occurring during the course of the clinical trial (i.e. from signing the informed consent onwards through the observational phase) were to be collected, documented and reported to the sponsor by the investigator on the appropriate electronic case report form / serious adverse event reporting forms.

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
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Restriction type: OTHER