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The primary objective of this trial is to establish superiority of the once-daily Tiotropium plus Salmeterol Inhalation Powder in daytime lung function response and non-inferiority in night-time lung function response over the comparator treatments inhaled in their established dose regimens when administered for 6-week periods to patients with chronic obstructive pulmonary disease (COPD). The main secondary objective is to evaluate the safety of the Tiotropium plus Salmeterol Inhalation Powder versus the comparator treatments.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI | Experimental | 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S_PE)/ 18 µg Tiotropium (Tio18GEL) / 50 µg Salmeterol MDPI (Salm50DPI) / 18 µg Tiotropium (T18GEL) plus 50 µg Salmeterol MDPI (S_DPI) BID |
|
| Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI | Experimental | 18 µg Tiotropium (Tio18GEL) / 18 µg Tiotropium (T18GEL) + 50 µg Salmeterol MDPI (S_DPI) BID / 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S_PE) / 50 µg Salmeterol MDPI (Salm50DPI) |
|
| Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL | Experimental | 50 µg Salmeterol MDPI (Salm50DPI) / 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S_PE) / 18 µg Tiotropium (T18GEL) + 50 µg Salmeterol MDPI (S_DPI) BID / 18 µg Tiotropium (Tio18GEL) |
|
| T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE | Experimental | 18 µg Tiotropium (T18GEL) + 50 µg Salmeterol MDPI (S_DPI) BID / 50 µg Salmeterol MDPI (Salm50DPI) / 18 µg Tiotropium (Tio18GEL) / 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S_PE) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tiotropium (Tio18GEL) | Drug | 18 µg Tiotropium (Tio18GEL) inhalation powder |
|
| Measure | Description | Time Frame |
|---|---|---|
| Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 - 12 Hours (AUC0-12) | FEV1 AUC was defined as the area under the FEV1 curve normalized for time. It was calculated from time 0 to 12 h (FEV1 AUC0-12), using the trapezoidal rule divided by the corresponding duration (12 h) to give the results in liter (L). FEV1 AUC0-12h response is defined as the change from baseline: FEV1 AUC0-12h response = FEV1 AUC0-12h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment. |
| Response in Forced Expiratory Volume in Second (FEV1) Area Under the Curve From 12 - 24 Hours (AUC12 -24) | The FEV1 AUC was defined as the area under the FEV1 curve (AUC) normalised for time. It was calculated from time 12 to 24 h (FEV1 AUC12-24), using the trapezoidal rule divided by the corresponding duration (i.e. 12 h) to give the results in L. AUC12-24h response is defined as the change from baseline: FEV1 AUC12-24h response = FEV1 AUC12-24h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit (Visit 2) just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment. |
| Response in Peak Forced Expiratory Volume in 1 Second (FEV1) | Peak FEV1 was defined as the highest FEV1 reading observed within 3 hours after inhalation of the last morning dose of each randomized treatment. Peak FEV1 response is defined as change from baseline: Peak FEV1 response = Peak FEV1 - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | At baseline and within 3 hours post-morning dose after 6 weeks of treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0-24 Hours (AUC0-24) | FEV1 AUC was defined as the area under the FEV1 curve normalized for time. It was calculated from time 0 to 24 h (FEV1 AUC0-24), using the trapezoidal rule divided by the corresponding duration (24 h) to give the results in liter (L). FEV1 AUC0-24h response is defined as the change from baseline: FEV1 AUC0-24h response = FEV1 AUC0-24h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. |
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Inclusion Criteria:
All patients must sign an informed consent consistent with ICH-GCP guidelines and local legislations prior to any study-related procedures, which includes medication washout and restrictions.
All patients must have a diagnosis of COPD and must meet the following criteria:
relatively stable* airway obstruction with a post-bronchodilator FEV1 < 80% of predicted normal and post-bronchodilator FEV1 < 70% of post-bronchodilator FVC at Visit 1 (according to GOLD criteria).
* The randomisation of patients with any respiratory infection or COPD exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period should be postponed. Patients may be randomised 6 weeks following recovery from the infection or exacerbation. Predicted normal values will be calculated according to ECSC.
Male or female patients 40 years of age or older.
Patients must be current or ex-smokers with a smoking history of 10 pack-years.
Patients must be able to perform technically acceptable pulmonary function tests
Patients must be able to inhale medication in a competent manner.
Patients must be able to perform all necessary recordings in the diary.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1184.13.1302 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||||
| 1184.13.1309 Boehringer Ingelheim Investigational Site |
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| Label | URL |
|---|---|
| Related Info | View source |
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All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Randomised, double-blind, 4-way crossover efficacy and safety comparison of Tiotropium/Salmeterol, Tiotropium Salmeterol and the free combination Tiotropium plus Salmeterol (50 μg) following chronic Administration in patients with COPD.
Patients received each of the 4 treatments for 6 weeks in a randomised sequence.
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| ID | Title | Description |
|---|---|---|
| FG000 | T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI | Period 1: Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Period 2: 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Period 3: One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID), in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Period 4: 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
|
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| Salmeterol MDPI (Salm50DPI) | Drug | 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) |
|
| Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI) | Drug | 18 µg Tiotropium (T18GEL) inhalation powder plus 50 µg Salmeterol MDPI (S_DPI) twice daily (BID) |
|
| Tiotropium/Salmeterol (T+S_PE) | Drug | Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S_PE) inhalation powder |
|
| Response in Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 is determined at the end of each treatment period and is defined as the pre-dose FEV1 measured just prior to the last administration of the morning dose of randomized treatment. Trough FEV1 response is defined as the change from baseline: Trough FEV1 response = Trough FEV1 - FEV1 (Baseline) The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment. |
| At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment. |
| Response in Forced Vital Capacity (FVC) Area Under the Curve From 0 to 12 Hours (AUC0-12) | FVC AUC was defined as the area under the FVC curve normalized for time. It was calculated from time 0 to 12 h (FVC AUC0-12), using the trapezoidal rule divided by the corresponding duration (12 h) to give the results in liter (L). FVC AUC0-12h response is defined as the change from baseline: FVC AUC0-12h response = FVC AUC0-12h - FVC (Baseline). The baseline value for FVC based parameters is defined as the pre-dose FVC measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment. |
| Response in Forced Vital Capacity (FVC) Area Under the Curve From 12 to 24 Hours (AUC12-24) | The FVC AUC was defined as the area under the FVC curve (AUC) normalised for time. It was calculated from time 12 to 24 h (FVC AUC12-24), using the trapezoidal rule divided by the corresponding duration (i.e. 12 h) to give the results in L. AUC12-24h response is defined as the change from baseline: FVC AUC12-24h response = FVC AUC12-24h - FVC (Baseline). The FVC baseline value is defined as the pre-dose FVC measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 10, 11 and 12 hours after inhalation of the evening dose after 6 weeks of treatment. |
| Response in Forced Vital Capacity (FVC) Area Under the Curve From 0 - 24 Hours (AUC0-24) | The FVC AUC was defined as the area under the FVC curve (AUC) normalised for time. It was calculated from time 0 to 24 h (FVC AUC0-24), using the trapezoidal rule divided by the corresponding duration (i.e. 24 h) to give the results in L. AUC response was defined as the change from the baseline FVC; baseline was defined as the FVC measured on randomisation visit. Mean is adjusted mean. | At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hour after inhalation the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment. |
| Response in Peak Forced Vital Capacity (FVC) | Peak FEV1 was defined as the highest FEV1 reading observed within 3 hours after inhalation of the last morning dose of each randomized treatment. Peak FEV1 response is defined as change from baseline: Peak FEV1 response = Peak FEV1 - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | At baseline and within 3 hours post-morning dose after 6 weeks of treatment. |
| Response in Trough Forced Vital Capacity (FVC) | Trough FVC1 is determined at the end of each 6-week treatment period and is defined as the pre-dose FVC1 measured just prior to the last administration of the morning dose of randomized treatment. Trough FVC1 response is defined as the change from baseline: Trough FVC1 response = Trough FVC1 - FVC1 (Baseline) The FVC1 baseline value is defined as the pre-dose FVC1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment. |
| Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve Form 0 to 12 Hours (AUC0-12) | PEF(L/min) AUC0-12(h) response is defined as the change from baseline. AUC0-12(h) was calculated as the area under the curve from 0 to 12 hours using the trapezoidal rule, divided by the full duration (12 hours) to report in liter/minutes. PEF AUC0-12h response = PEF AUC0-12h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | At baseline and 10 minutes (min) prior and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment. |
| Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 12 to 24 Hours (AUC12-24) | PEF(L/min) AUC12-24(h) response is defined as the change from baseline. AUC12-24(h) was calculated as the area under the curve from 12 to 24 hours using the trapezoidal rule, divided by the full duration (12 hours) to report in liter/minutes. PEF AUC12-24h response = PEF AUC12-24h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | At baseline and 10 minutes (min) prior and 30 min, 60 min, 2, 10, 11 and 12 hours after inhalation of the evening dose after 6 weeks of treatment. |
| Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 0 to 24 Hours (AUC0-24) | PEF(L/min) AUC0-24(h) response is defined as the change from baseline. AUC0-24(h) was calculated as the area under the curve from 0 to 24 hours using the trapezoidal rule, divided by the full duration (24 hours) to report in liter/minutes. PEF AUC0-24h response = PEF AUC0-24h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment. |
| Response in Peak PEF (Peak Expiratory Flow Rate) | Peak PEF was defined as the highest PEF reading observed within 3 hours after inhalation of the last morning dose of randomized treatment. Peak PEF response is defined as change from baseline: Peak PEF response = Peak PEF - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | At baseline and within 3 hours post-morning dose after 6 weeks of treatment. |
| Response in Trough Peak Expiratory Flow Rate (PEF) | Trough PEF is determined at the end of each treatment period and is defined as the pre-dose PEF measured just prior to the last administration of the morning dose of randomized treatment. Trough PEF response is defined as the change from baseline: Trough PEF response = Trough PEF - PEF (Baseline) The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment. |
| Response in Individual Forced Expiratory Volume in 1 Second (FEV1) Over a 24 Hour Observation Period | Response in individual forced expiratory volume in 1 second (FEV1) over a 24 hour observation period. Response is defined as change from baseline. Means are adjusted for treatment, centre, treatment period and patient within centre. | At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23, and 24 hours post morning dose after 6 weeks of treatment. |
| Response in Individual Forced Vital Capacity (FVC) Over a 24 Hour Observation Period | Response in forced vital capacity (FVC) over a 24 hour observation period. Response is defined as change from baseline. | At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23 and 24 hours post morning dose after 6 weeks of treatment. |
| Response in Individual Peak Expiratory Flow (PEF) Over a 24 Hour Observation Period | Response in individual peak expiratory flow (PEF) over a 24 hour observation period. Response is defined as change from baseline. Means are adjusted for treatment, centre, treatment period and patient within centre. | At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23, and 24 hours post morning dose after 6 weeks of treatment. |
| Response in Morning and Evening Peak Expiratory Flow Rate (PEF), Recorded by Patients at Home | The mean PEF is defined as the mean of the values obtained during the weeks after the first three weeks of treatment. Morning and evening mean PEF were calculated and analyzed separately. PEF was measured twice daily (in the morning prior to inhalation of study medication and in the evening prior to inhalation of study medication). Morning and evening mean PEF response are defined as the change from morning and evening baseline, respectively. Morning and evening mean PEF baseline are defined as the mean of the morning and evening values, respectively obtained from the last week preceding the randomization visit. Mean is adjusted for treatment, center, treatment period and patient within center. | At baseline and last 3 weeks of 6-week treatment period. |
| Response in Morning and Evening Forced Expiratory Volume in 1 Second (FEV1) Recorded by Participants at Home | Per treatment period, the morning mean FEV1 (mean of the pre-dose morning FEV1 measurements) and evening mean FEV1 (mean of the pre-dose evening FEV1 measurement) were calculated. Per treatment period the data obtained after the first 3 weeks were used for calculating these means. Morning and evening mean FEV1 responses are defined as the change from morning and evening baseline, respectively. The baseline values, morning and evening mean FEV1(Baseline), are defined as the mean of the morning and evening values, respectively obtained from the last week preceding the randomization visit . Mean is adjusted for treatment, centre, treatment period and patient within centre. | At baseline and last 3 weeks of 6-week treatment period. |
| Response in Mean Number of Days With Rescue Medication Use | Response (change from baseline) in mean number of days with rescue medication use in day-time, night-time and 24-hours. Per treatment period, the response in mean number of days using rescue medication was calculated for day-time (from inhalation of morning dose until 12 hours thereafter), night-time (from inhalation of evening dose until 12 hours thereafter) and 24h-total (from inhalation of morning dose until 24 hours thereafter) separately. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating means. Mean is adjusted mean. | At baseline and last 3 weeks of 6-week treatment period. |
| Response in Mean Number of Puffs of Rescue Medication | Response in mean number of puffs of rescue medication. Per treatment period, the response in mean number of puffs rescue medication used was calculated, for day-time (from inhalation of morning dose until 12 hours thereafter), night-time (from inhalation of evening dose until 12 hours thereafter) and 24h-total (from inhalation of morning dose until 24 hours thereafter) separately. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating means. Night-time, day-time and 24h-total mean number of puffs rescue medication used responses are defined as the change from night-time, day-time and 24h-total baseline, respectively. The baseline values, night-time, day-time and 24h-total mean mean number of puffs rescue medication used (Baseline), are defined as the mean of the night-time, day-time and 24h-total values, respectively obtained from the last week preceding the randomisation visit. | At baseline and last 3 weeks of 6-week treatment period. |
| Response in Mean Number of Days With Night-time Awakenings | Response in mean number of days with night-time awakenings. Per treatment period, the mean number days with awakening during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating this mean. Mean number of days with night-time awakenings response is defined as the change from baseline. The baseline value, mean number of days with night-time awakenings (Baseline), is defined as the mean of the number of days with night-time awakenings obtained from the last week preceding the randomization visit. | At baseline and last 3 weeks of 6-week treatment period. |
| Response in Mean Number of Days With Night-time Awakenings Due to Shortness of Breath (SOB) | Per treatment period, the mean number days with awakening (only chronic obstructive pulmonary disease (COPD) related awakenings) during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating the mean. Mean number of days with COPD related awakenings response is defined as the change from baseline. The baseline value, mean number of days with COPD related awakenings (Baseline), is defined as the mean of the number of days with COPD related awakenings obtained from the last week preceding the randomization visit. | At baseline and last 3 weeks of 6-week treatment period. |
| Response in Means Number of Awakenings Due to Shortness of Breath (SOB) | Per treatment period, the mean number of awakening (only chronic obstructive pulmonary disease (COPD) related awakenings) during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating this mean. Mean number of COPD related awakenings response is defined as the change from baseline. The baseline value, mean number of COPD related awakenings (Baseline), is defined as the mean of the number of days with COPD related awakenings obtained from the last week preceding the randomization visit. | At baseline and last 3 weeks of 6-week treatment period. |
| Response in Average Shortness of Breath (SOB) Score at Night | Response in average shortness of breath (SOB) score at night. The SOB measured the shortness of breath, ranging from 1 to 5, where 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit and 5 = very much. A higher score indicates a worse outcome. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating the mean. | At baseline and last 3 weeks of 6-week treatment period. |
| Number of Participants With Drug Related Adverse Events | Number of participants with drug related adverse events. | From first drug administration until last drug administration (average duration of 42 days) + 30 days, up to 91 days for T+S_PE, up to 98 days for Tio18GEL, up 89 days for Salm50DPI and up to 113 days for T18GEL+S_DPI. |
| Number of Patients With Marked Changes in Vital Signs | Marked changes from baseline in vital signs were defined as followed: Systolic blood pressure
Diastolic blood pressure
Pulse
Baseline is defined as the pre-dose measurement at randomisation visit. | At baseline and 6 hours following the morning dose of study medication after 6 weeks of treatment. |
| Berlin |
| Germany |
| 1184.13.1308 Boehringer Ingelheim Investigational Site | Cottbus | Germany |
| 1184.13.1311 Boehringer Ingelheim Investigational Site | Großhansdorf | Germany |
| 1184.13.1312 Boehringer Ingelheim Investigational Site | Hamburg | Germany |
| 1184.13.1305 Boehringer Ingelheim Investigational Site | Mainz | Germany |
| 1184.13.1301 Boehringer Ingelheim Investigational Site | Mannheim | Germany |
| 1184.13.1306 Boehringer Ingelheim Investigational Site | Rodgau-Dudenhofen | Germany |
| 1184.13.1310 Boehringer Ingelheim Investigational Site | Rüdersdorf | Germany |
| 1184.13.1307 Boehringer Ingelheim Investigational Site | Schwerin | Germany |
| 1184.13.1304 Boehringer Ingelheim Investigational Site | Wiesbaden | Germany |
| 1184.13.1303 Boehringer Ingelheim Investigational Site | Wiesloch | Germany |
| FG001 | Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI | Period 1: 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Period 2: 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Period 3: Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Period 4: One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID), in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| FG002 | Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL | Period 1: One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID), in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Period 2: Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Period 3: 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Period 4: 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| FG003 | T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE | Period 1: 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Period 2: One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID), in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Period 3: 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Period 4: Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| Treated |
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| COMPLETED | Not prematurely discontinued study medication |
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| NOT COMPLETED |
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| Period 2 |
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| Period 3 |
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| Period 4 |
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Treated Set: All randomised patients who took at least one dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Study Total | Total number of patients treated in the study. This was a randomized, double-blind 4-way cross over study. Patients were assigned randomly to one of 4 treatment sequences in which they received each of the 4 treatments (7.5 µg/25 µg Tio/Salmeterol, 18 µg Tiotropium, 50 µg Salmeterol MDPI and 18 µg Tiotropium Free combination). The duration of each treatment period was 6 weeks on average with no washout period between treatments. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| FEV1 AUC0-12 at baseline | FEV1 AUC was defined as the area under the FEV1 curve normalized for time. It was calculated from time 0 to 12 h (FEV1 AUC0-12), using the trapezoidal rule divided by the corresponding duration (12 h) to give the results in liter (L). FEV1 AUC0-12 at baseline is reported. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. | Mean | Standard Deviation | Liter (L) |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 - 12 Hours (AUC0-12) | FEV1 AUC was defined as the area under the FEV1 curve normalized for time. It was calculated from time 0 to 12 h (FEV1 AUC0-12), using the trapezoidal rule divided by the corresponding duration (12 h) to give the results in liter (L). FEV1 AUC0-12h response is defined as the change from baseline: FEV1 AUC0-12h response = FEV1 AUC0-12h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter (L) | At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment. |
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| Primary | Response in Forced Expiratory Volume in Second (FEV1) Area Under the Curve From 12 - 24 Hours (AUC12 -24) | The FEV1 AUC was defined as the area under the FEV1 curve (AUC) normalised for time. It was calculated from time 12 to 24 h (FEV1 AUC12-24), using the trapezoidal rule divided by the corresponding duration (i.e. 12 h) to give the results in L. AUC12-24h response is defined as the change from baseline: FEV1 AUC12-24h response = FEV1 AUC12-24h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit (Visit 2) just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter (L) | At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment. |
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| Primary | Response in Peak Forced Expiratory Volume in 1 Second (FEV1) | Peak FEV1 was defined as the highest FEV1 reading observed within 3 hours after inhalation of the last morning dose of each randomized treatment. Peak FEV1 response is defined as change from baseline: Peak FEV1 response = Peak FEV1 - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter | At baseline and within 3 hours post-morning dose after 6 weeks of treatment. |
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| Primary | Response in Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 is determined at the end of each treatment period and is defined as the pre-dose FEV1 measured just prior to the last administration of the morning dose of randomized treatment. Trough FEV1 response is defined as the change from baseline: Trough FEV1 response = Trough FEV1 - FEV1 (Baseline) The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter | At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment. |
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| Secondary | Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0-24 Hours (AUC0-24) | FEV1 AUC was defined as the area under the FEV1 curve normalized for time. It was calculated from time 0 to 24 h (FEV1 AUC0-24), using the trapezoidal rule divided by the corresponding duration (24 h) to give the results in liter (L). FEV1 AUC0-24h response is defined as the change from baseline: FEV1 AUC0-24h response = FEV1 AUC0-24h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter | At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment. |
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| Secondary | Response in Forced Vital Capacity (FVC) Area Under the Curve From 0 to 12 Hours (AUC0-12) | FVC AUC was defined as the area under the FVC curve normalized for time. It was calculated from time 0 to 12 h (FVC AUC0-12), using the trapezoidal rule divided by the corresponding duration (12 h) to give the results in liter (L). FVC AUC0-12h response is defined as the change from baseline: FVC AUC0-12h response = FVC AUC0-12h - FVC (Baseline). The baseline value for FVC based parameters is defined as the pre-dose FVC measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter | At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment. |
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| Secondary | Response in Forced Vital Capacity (FVC) Area Under the Curve From 12 to 24 Hours (AUC12-24) | The FVC AUC was defined as the area under the FVC curve (AUC) normalised for time. It was calculated from time 12 to 24 h (FVC AUC12-24), using the trapezoidal rule divided by the corresponding duration (i.e. 12 h) to give the results in L. AUC12-24h response is defined as the change from baseline: FVC AUC12-24h response = FVC AUC12-24h - FVC (Baseline). The FVC baseline value is defined as the pre-dose FVC measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter | At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 10, 11 and 12 hours after inhalation of the evening dose after 6 weeks of treatment. |
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| Secondary | Response in Forced Vital Capacity (FVC) Area Under the Curve From 0 - 24 Hours (AUC0-24) | The FVC AUC was defined as the area under the FVC curve (AUC) normalised for time. It was calculated from time 0 to 24 h (FVC AUC0-24), using the trapezoidal rule divided by the corresponding duration (i.e. 24 h) to give the results in L. AUC response was defined as the change from the baseline FVC; baseline was defined as the FVC measured on randomisation visit. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter | At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hour after inhalation the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment. |
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| Secondary | Response in Peak Forced Vital Capacity (FVC) | Peak FEV1 was defined as the highest FEV1 reading observed within 3 hours after inhalation of the last morning dose of each randomized treatment. Peak FEV1 response is defined as change from baseline: Peak FEV1 response = Peak FEV1 - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analyzed may vary across endpoints. | Posted | Mean | Standard Error | Liter | At baseline and within 3 hours post-morning dose after 6 weeks of treatment. |
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| Secondary | Response in Trough Forced Vital Capacity (FVC) | Trough FVC1 is determined at the end of each 6-week treatment period and is defined as the pre-dose FVC1 measured just prior to the last administration of the morning dose of randomized treatment. Trough FVC1 response is defined as the change from baseline: Trough FVC1 response = Trough FVC1 - FVC1 (Baseline) The FVC1 baseline value is defined as the pre-dose FVC1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Deviation | Liter | At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment. |
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| Secondary | Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve Form 0 to 12 Hours (AUC0-12) | PEF(L/min) AUC0-12(h) response is defined as the change from baseline. AUC0-12(h) was calculated as the area under the curve from 0 to 12 hours using the trapezoidal rule, divided by the full duration (12 hours) to report in liter/minutes. PEF AUC0-12h response = PEF AUC0-12h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter/minutes (L/min) | At baseline and 10 minutes (min) prior and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment. |
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| Secondary | Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 12 to 24 Hours (AUC12-24) | PEF(L/min) AUC12-24(h) response is defined as the change from baseline. AUC12-24(h) was calculated as the area under the curve from 12 to 24 hours using the trapezoidal rule, divided by the full duration (12 hours) to report in liter/minutes. PEF AUC12-24h response = PEF AUC12-24h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter/minutes (L/min) | At baseline and 10 minutes (min) prior and 30 min, 60 min, 2, 10, 11 and 12 hours after inhalation of the evening dose after 6 weeks of treatment. |
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| Secondary | Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 0 to 24 Hours (AUC0-24) | PEF(L/min) AUC0-24(h) response is defined as the change from baseline. AUC0-24(h) was calculated as the area under the curve from 0 to 24 hours using the trapezoidal rule, divided by the full duration (24 hours) to report in liter/minutes. PEF AUC0-24h response = PEF AUC0-24h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter/minutes (L/min) | At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment. |
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| Secondary | Response in Peak PEF (Peak Expiratory Flow Rate) | Peak PEF was defined as the highest PEF reading observed within 3 hours after inhalation of the last morning dose of randomized treatment. Peak PEF response is defined as change from baseline: Peak PEF response = Peak PEF - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter/minutes (L/min) | At baseline and within 3 hours post-morning dose after 6 weeks of treatment. |
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| Secondary | Response in Trough Peak Expiratory Flow Rate (PEF) | Trough PEF is determined at the end of each treatment period and is defined as the pre-dose PEF measured just prior to the last administration of the morning dose of randomized treatment. Trough PEF response is defined as the change from baseline: Trough PEF response = Trough PEF - PEF (Baseline) The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean. | Full Analysis Set: All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter/minutes (L/min) | At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment. |
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| Secondary | Response in Individual Forced Expiratory Volume in 1 Second (FEV1) Over a 24 Hour Observation Period | Response in individual forced expiratory volume in 1 second (FEV1) over a 24 hour observation period. Response is defined as change from baseline. Means are adjusted for treatment, centre, treatment period and patient within centre. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter (L) | At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23, and 24 hours post morning dose after 6 weeks of treatment. |
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| Secondary | Response in Individual Forced Vital Capacity (FVC) Over a 24 Hour Observation Period | Response in forced vital capacity (FVC) over a 24 hour observation period. Response is defined as change from baseline. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter | At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23 and 24 hours post morning dose after 6 weeks of treatment. |
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| Secondary | Response in Individual Peak Expiratory Flow (PEF) Over a 24 Hour Observation Period | Response in individual peak expiratory flow (PEF) over a 24 hour observation period. Response is defined as change from baseline. Means are adjusted for treatment, centre, treatment period and patient within centre. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter/minutes (L/min) | At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23, and 24 hours post morning dose after 6 weeks of treatment. |
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| Secondary | Response in Morning and Evening Peak Expiratory Flow Rate (PEF), Recorded by Patients at Home | The mean PEF is defined as the mean of the values obtained during the weeks after the first three weeks of treatment. Morning and evening mean PEF were calculated and analyzed separately. PEF was measured twice daily (in the morning prior to inhalation of study medication and in the evening prior to inhalation of study medication). Morning and evening mean PEF response are defined as the change from morning and evening baseline, respectively. Morning and evening mean PEF baseline are defined as the mean of the morning and evening values, respectively obtained from the last week preceding the randomization visit. Mean is adjusted for treatment, center, treatment period and patient within center. | Full Analysis Set (FAS): All patients where baseline data and any on-Treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints | Posted | Mean | Standard Error | Liter / minute (L/min) | At baseline and last 3 weeks of 6-week treatment period. |
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| Secondary | Response in Morning and Evening Forced Expiratory Volume in 1 Second (FEV1) Recorded by Participants at Home | Per treatment period, the morning mean FEV1 (mean of the pre-dose morning FEV1 measurements) and evening mean FEV1 (mean of the pre-dose evening FEV1 measurement) were calculated. Per treatment period the data obtained after the first 3 weeks were used for calculating these means. Morning and evening mean FEV1 responses are defined as the change from morning and evening baseline, respectively. The baseline values, morning and evening mean FEV1(Baseline), are defined as the mean of the morning and evening values, respectively obtained from the last week preceding the randomization visit . Mean is adjusted for treatment, centre, treatment period and patient within centre. | Full Analysis Set (FAS): All patients where baseline data and any on-Treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Liter (L) | At baseline and last 3 weeks of 6-week treatment period. |
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| Secondary | Response in Mean Number of Days With Rescue Medication Use | Response (change from baseline) in mean number of days with rescue medication use in day-time, night-time and 24-hours. Per treatment period, the response in mean number of days using rescue medication was calculated for day-time (from inhalation of morning dose until 12 hours thereafter), night-time (from inhalation of evening dose until 12 hours thereafter) and 24h-total (from inhalation of morning dose until 24 hours thereafter) separately. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating means. Mean is adjusted mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Days | At baseline and last 3 weeks of 6-week treatment period. |
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| Secondary | Response in Mean Number of Puffs of Rescue Medication | Response in mean number of puffs of rescue medication. Per treatment period, the response in mean number of puffs rescue medication used was calculated, for day-time (from inhalation of morning dose until 12 hours thereafter), night-time (from inhalation of evening dose until 12 hours thereafter) and 24h-total (from inhalation of morning dose until 24 hours thereafter) separately. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating means. Night-time, day-time and 24h-total mean number of puffs rescue medication used responses are defined as the change from night-time, day-time and 24h-total baseline, respectively. The baseline values, night-time, day-time and 24h-total mean mean number of puffs rescue medication used (Baseline), are defined as the mean of the night-time, day-time and 24h-total values, respectively obtained from the last week preceding the randomisation visit. | Full Analysis Set (FAS): All patients where baseline data any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Puffs | At baseline and last 3 weeks of 6-week treatment period. |
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| Secondary | Response in Mean Number of Days With Night-time Awakenings | Response in mean number of days with night-time awakenings. Per treatment period, the mean number days with awakening during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating this mean. Mean number of days with night-time awakenings response is defined as the change from baseline. The baseline value, mean number of days with night-time awakenings (Baseline), is defined as the mean of the number of days with night-time awakenings obtained from the last week preceding the randomization visit. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Days | At baseline and last 3 weeks of 6-week treatment period. |
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| Secondary | Response in Mean Number of Days With Night-time Awakenings Due to Shortness of Breath (SOB) | Per treatment period, the mean number days with awakening (only chronic obstructive pulmonary disease (COPD) related awakenings) during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating the mean. Mean number of days with COPD related awakenings response is defined as the change from baseline. The baseline value, mean number of days with COPD related awakenings (Baseline), is defined as the mean of the number of days with COPD related awakenings obtained from the last week preceding the randomization visit. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Days | At baseline and last 3 weeks of 6-week treatment period. |
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| Secondary | Response in Means Number of Awakenings Due to Shortness of Breath (SOB) | Per treatment period, the mean number of awakening (only chronic obstructive pulmonary disease (COPD) related awakenings) during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating this mean. Mean number of COPD related awakenings response is defined as the change from baseline. The baseline value, mean number of COPD related awakenings (Baseline), is defined as the mean of the number of days with COPD related awakenings obtained from the last week preceding the randomization visit. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Awakenings | At baseline and last 3 weeks of 6-week treatment period. |
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| Secondary | Response in Average Shortness of Breath (SOB) Score at Night | Response in average shortness of breath (SOB) score at night. The SOB measured the shortness of breath, ranging from 1 to 5, where 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit and 5 = very much. A higher score indicates a worse outcome. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating the mean. | Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints. | Posted | Mean | Standard Error | Score on a scale | At baseline and last 3 weeks of 6-week treatment period. |
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| Secondary | Number of Participants With Drug Related Adverse Events | Number of participants with drug related adverse events. | Treated Set (TS): All randomised patients who took at least one dose of study medication. | Posted | Count of Participants | Participants | From first drug administration until last drug administration (average duration of 42 days) + 30 days, up to 91 days for T+S_PE, up to 98 days for Tio18GEL, up 89 days for Salm50DPI and up to 113 days for T18GEL+S_DPI. |
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| Secondary | Number of Patients With Marked Changes in Vital Signs | Marked changes from baseline in vital signs were defined as followed: Systolic blood pressure
Diastolic blood pressure
Pulse
Baseline is defined as the pre-dose measurement at randomisation visit. | Treated Set (TS): All randomised patients who took at least one dose of study medication and who had available data. | Posted | Count of Participants | Participants | At baseline and 6 hours following the morning dose of study medication after 6 weeks of treatment. |
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From first drug administration until last drug administration (average duration of 42 days) + 30 days, up to 91 days for T+S_PE, up to 98 days for Tio18GEL, up 89 days for Salm50DPI and up to 113 days for T18GEL+S_DPI.
Treated Set (TS): All randomised patients who took at least one dose of study medication.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 7.5 µg /25 µg Tio /Salmeterol (T+S_PE) | Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. | 0 | 132 | 1 | 132 | 14 | 132 |
| EG001 | 18 µg Tiotropium (Tio18GEL) | 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. | 1 | 135 | 7 | 135 | 15 | 135 |
| EG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. | 0 | 137 | 4 | 137 | 14 | 137 |
| EG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. | 0 | 132 | 2 | 132 | 11 | 132 |
| EG004 | Total Treated | All patients who received at least one dose of study medication. | 1 | 146 | 13 | 146 | 47 | 146 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
| |
| Mastoiditis | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
| |
| Meningitis pneumococcal | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
| |
| Pneumococcal infection | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
| |
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 12.1 | Systematic Assessment |
| |
| Hepatic neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 12.1 | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 12.1 | Systematic Assessment |
| |
| Haemorrhagic anaemia | Blood and lymphatic system disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Intracranial aneurysm | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Subarachnoid haemorrhage | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Congestive cardiomyopathy | Cardiac disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Right ventricular failure | Cardiac disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Diarrhoea haemorrhagic | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Diverticulum intestinal haemorrhagic | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Intestinal haemorrhage | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 12.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069447 | Tiotropium Bromide |
| D000068299 | Salmeterol Xinafoate |
| ID | Term |
|---|---|
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D000420 | Albuterol |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D000588 | Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
Not provided
Not provided
| Other adverse event (AE) |
|
| Other adverse event (AE) |
|
| Worsening of disease under study (AE) |
|
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
H1: Superiority of FDC Tiotropium/Salmeterol (T+S_PE) vs Tiotropium (Tio18GEL) for FEV1 AUC0- 12 |
| ANOVA |
Analysis of variance with terms for centre, patient with centre, treatment, and period. α = 0.025 one-sided |
| <.0001 |
| Difference of adjusted means |
| 0.070 |
| Standard Error of the Mean |
| 0.014 |
| 2-Sided |
| 95 |
| 0.042 |
| 0.097 |
(T+S_PE) - (Tio18GEL) |
| Superiority |
| The Tiotropium free combination (T18GEL+S_DPI) was included in order to characterise this treatment in comparison with the FDC Tiotropium/Salmeterol (T+S_PE). No formal hypotheses were defined. | ANOVA | Analysis of variance with terms for centre, patient with centre, treatment, and period. α = 0.025 one-sided | 0.0914 | Difference of adjusted means | -0.024 | Standard Error of the Mean | 0.014 | 2-Sided | 95 | -0.052 | 0.004 | (T+S_PE) - (T18GEL+S-DPI) | Other |
| OG001 | 18 µg Tiotropium (Tio18GEL) | 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
|
|
|
18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
|
|
|
| 18µg Tiotropium (Tio18GEL) |
18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
|
|
|
| OG001 | 18µg Tiotropium (Tio18GEL) | 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
|
|
|
| OG001 | 18µg Tiotropium (Tio18GEL) | 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
|
|
|
| OG001 | 18µg Tiotropium (Tio18GEL) | 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
|
|
|
| OG001 |
| 18µg Tiotropium (Tio18GEL) |
18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
|
|
|
18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
|
|
|
| 18µg Tiotropium (Tio18GEL) |
18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
|
|
|
| OG001 | 18µg Tiotropium (Tio18GEL) | 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
|
|
|
| OG001 | 18µg Tiotropium (Tio18GEL) | 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
|
|
|
| OG001 | 18µg Tiotropium (Tio18GEL) | 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
|
|
|
18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
|
|
|
| 18µg Tiotropium (Tio18GEL) |
18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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| OG001 | 18µg Tiotropium (Tio18GEL) | 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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| OG001 | 18µg Tiotropium (Tio18GEL) | 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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| 18 µg Tiotropium (Tio18GEL) |
18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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| OG001 | 18 µg Tiotropium (Tio18GEL) | 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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| 18 µg Tiotropium (Tio18GEL) |
18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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| OG001 | 18 µg Tiotropium (Tio18GEL) | 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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| 18 µg Tiotropium (Tio18GEL) |
18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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| OG001 | 18 µg Tiotropium (Tio18GEL) | 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG002 | 50 µg Salmeterol MDPI (Salm50DPI) | One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
| OG003 | 18 µg Tiotropium Free Combination (T18GEL+S_DPI) | 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods. |
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