Tiotropium Once Daily 18 Mcg Versus Salmeterol Twice Daily 50 Mcg on Time to First Exacerbation in COPD Patients.
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT00563381
Collaborator
Pfizer (Industry)
7,376
752
2
9.8
Study Details
Study Description
Brief Summary
This is a randomised, double-blind, double-dummy, multinational, multicentre, parallel group trial comparing tiotropium (18 mcg) inhalation capsule via HandiHaler and salmeterol (50 mcg) via MDI in patients with COPD. There will be a two-week run-in period followed by a 52-week randomised treatment phase. Patients who withdraw prematurely from trial medication will be encouraged to remain in the trial and participate in follow-up telephone contacts until their predicted normal exit date from the trial (i.e. 52 weeks after taking the first dose of randomised treatment). The phone calls will be made at all scheduled visits.
The primary objective of this study is to compare the effect of tiotropium (18 mcg) inhalation capsule via HandiHaler with that of salmeterol (50 mcg) via MDI on COPD exacerbations.
The primary endpoint is time to first COPD exacerbation during the 52 week randomised treatment period. A COPD exacerbation will be defined as a complex of respiratory events / symptoms (increase or new onset) of more than one of the following: cough, sputum, wheezing, dyspnoea or chest tightness with at least one symptom lasting at least three days requiring treatment with antibiotics and/or systemic steroids and/or hospitalisation.
The onset of an exacerbation is defined as the onset of the first new or increased reported symptom. The end of the exacerbation should be recorded as defined by the investigator.
Only COPD exacerbations with onset during randomised treatment will be included in the analysis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
7376 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double
Primary Purpose:
Treatment
Official Title:
Effect of Inhalation of Tiotropium Once Daily 18 Mcg Versus Salmeterol Twice Daily 50 Mcg on Time to First Exacerbation in COPD Patients (a Randomised, Double-blind, Double-dummy, Parallel Group, One-year Study).
Study Start Date
:
Jan 1, 2008
Actual Primary Completion Date
:
Apr 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Tiotropium + Placebo patients inhale Tiotropium 18mcg once daily via HandiHaler and Placebo MDI twice daily |
Drug: Tiotropium bromide
18 mcg/daily
Drug: Placebo Salmeterol
Placebo identical to Salmeterol device
|
| Active Comparator: Salmeterol + Placebo patients inhale Salmeterol 50mcg twice daily via MDI and Placebo HandiHaler once daily |
Drug: Salmeterol
100 mcg/daily
Drug: Placebo Tiotropium
Placebo identical to Tiotropium device
|
Outcome Measures
Primary Outcome Measures
- First Occurrence of (Moderate or Severe) COPD Exacerbation [52 weeks]
First occurrence analysed by Cox regression as time to first exacerbation and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
Secondary Outcome Measures
- COPD Exacerbations Per Patient-year Leading to Hospitalisation [52 weeks]
An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
- Number of Participants With at Least One COPD Exacerbation [52 weeks]
An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
- COPD Exacerbations Per Patient-year [52 weeks]
- First Occurrence of COPD Exacerbation Leading to Hospitalization [52 weeks]
First occurrence analysed by Cox regression as time to first exacerbation leading to hospitalisation and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
- Number of Participants With at Least One COPD Exacerbation Leading to Hospitalisation [52 weeks]
An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
- Occurrence of Premature Discontinuation of Trial Medication [52 weeks]
Occurrence analysed by Cox regression as time to premature discontinuation of trial medication and reported as hazard ratio
- Number of Participants With Premature Discontinuation of Trial Medication [52 weeks]
- First Occurrence of COPD Exacerbation or Discontinuation of Trial Medication Because of Worsening of Underlying Disease, Whichever Comes First [52 weeks]
First occurrence analysed by Cox regression as time to first exacerbation or discontinuation of trial medication because of worsening of underlying disease, whichever comes first and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
- First Occurrence of COPD Exacerbations Treated With Systemic Steroids [52 weeks]
First occurrence analysed by Cox regression as time to first exacerbation treated with systemic steroids and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
- First Occurrence of COPD Exacerbations Treated With Antibiotics [52 weeks]
First occurrence analysed by Cox regression as time to first exacerbation treated with antibiotics and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
- First Occurrence of COPD Exacerbations Treated With Systemic Steroids and Antibiotics [52 weeks]
First occurrence analysed by Cox regression as time to first exacerbation treated with systemic steroids and antibiotics and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
- COPD Exacerbations Treated With Systemic Steroids Per Patient-year [52 weeks]
An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
- COPD Exacerbations Treated With Antibiotics Per Patient-year [52 weeks]
An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
- COPD Exacerbations Treated With Systemic Steroids and Antibiotics Per Patient-year [52 weeks]
An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 1 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 2 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 3 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 4 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 5 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 6 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 7 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 8 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 9 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 10 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 11 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 12 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 13 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 14 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 15 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
- Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 16 [16 weeks]
PEFR means peak expiratory flow rate and is measured in liter per minute
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- All patients must have a diagnosis of chronic obstructive pulmonary disease (COPD) and must meet the following criteria at Visit 1:
Patients must have relatively stable, moderate to very severe airway obstruction with a post-bronchodilator FEV1 <=70% of predicted normal and FEV1 <=70% of FVC post-bronchodilator (i.e. 30 minutes after inhalation of 4 puffs of 100 µg salbutamol or equivalent SABA). Predicted normal values will be calculated according to ECSC.
For Height measured in inches Males: FEV1 predicted (L) = 4.30 x (height (inches) / 39.37)-0.029 x age (yrs) - 2.49 Females:FEV1 predicted (L) = 3.95 x (height (inches) / 39.37)-0.025 x age (yrs) - 2.60 For Height measured in metres Males: FEV1 predicted (L) = 4.30 x (height (metres)) - 0.029 x age (years) - 2.49 Females: FEV1 predicted (L) = 3.95 x (height (metres)) - 0.025 x age (years) - 2.60
-
All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial.
-
Male or female patients 40 years of age or older.
-
Patients with a history of at least one exacerbation within the past year requiring treatment with either antibiotics and/or systemic steroids and/or hospitalisation.
-
Patients must be current or ex-smokers with a smoking history of >= 10 pack-years. (Patients who have never smoked cigarettes must be excluded.)
-
Patients must be able to perform all study-related procedures including technically acceptable pulmonary function tests (PFTs).
-
Patients must be able to inhale medication in a competent manner from the HandiHaler and a metered dose inhaler (MDI).
-
Patients must be able to maintain records (patient daily diary card) during the study period as required in the protocol.
Exclusion Criteria:
-
Significant diseases other than COPD. A significant disease is defined as a disease or condition which, in the opinion of the investigator, may put the patient at risk because of participation in the study or may influence either the results of the study or the patients' ability to participate in the study.
-
Patients with a diagnosis of asthma.
-
Patients with a life-threatening pulmonary obstruction, or a history of cystic fibrosis.
-
Patients with known active tuberculosis.
-
Patients with a known symptomatic prostatic hyperplasia or bladder neck obstruction. Patients with symptomatically-controlled prostatic hyperplasia on medication may be included and should continue their medication.
-
Patients with known narrow-angle glaucoma.
-
Patients with a history of myocardial infarction within the year prior to Visit 1.
-
Patients with a history of hospital admission for heart failure within the year prior to Visit 1.
-
Patients with cardiac arrhythmia requiring medical or surgical treatment.
-
Patients with severe cardiovascular disorders.
-
Patients with a known hypersensitivity to anticholinergic drugs, beta-adrenergics, lactose or any other component of the medication delivery system.
-
Patients with known moderate or severe renal insufficiency (known creatinine clearance of <= 50 mL/min).
-
Patients with untreated known hypokalaemia.
-
Patients with untreated known thyrotoxicosis.
-
Patients with brittle/unstable diabetes mellitus.
-
Patients with a history of and/or active significant alcohol or drug abuse. See exclusion criterion 1.
-
Patients who have taken an investigational drug within 30 days or six half-lives (whichever is greater) prior to Screening Visit (Visit 1).
-
Use of systemic corticosteroid medication at unstable doses (i.e less than six weeks on stable dose) or at doses in excess of the equivalent of 10 mg prednisolone per day or 20 mg every other day.
-
Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e oral contraceptives, intrauterine devices, diaphragm or subdermal implants e.g Norplant) for at least three months prior to, and for the duration of the trial.
-
Previous participation (receipt of randomised treatment) in this study.
-
Patients who are currently participating in another study.
-
Patients with any respiratory infection or COPD exacerbation in the four weeks prior to the Screening Visit (Visit 1) or during the run-in period should be postponed. In the case of a respiratory infection or COPD exacerbation during the run-in period, the latter may be extended up to four weeks.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 205.389.1020 Boehringer Ingelheim Investigational Site | Feldbach | Austria | ||
| 2 | 205.389.1010 Boehringer Ingelheim Investigational Site | Feldkirch | Austria | ||
| 3 | 205.389.1011 Boehringer Ingelheim Investigational Site | Grimmenstein/Hochegg | Austria | ||
| 4 | 205.389.1003 Boehringer Ingelheim Investigational Site | Gänserndorf | Austria | ||
| 5 | 205.389.1005 Boehringer Ingelheim Investigational Site | Hallein | Austria | ||
| 6 | 205.389.1023 Boehringer Ingelheim Investigational Site | Linz | Austria | ||
| 7 | 205.389.1001 Boehringer Ingelheim Investigational Site | Mittersill | Austria | ||
| 8 | 205.389.1027 Boehringer Ingelheim Investigational Site | Salzburg | Austria | ||
| 9 | 205.389.1026 Boehringer Ingelheim Investigational Site | Schlüßlberg | Austria | ||
| 10 | 205.389.1016 Boehringer Ingelheim Investigational Site | Spittal/Drau | Austria | ||
| 11 | 205.389.1022 Boehringer Ingelheim Investigational Site | Steyr | Austria | ||
| 12 | 205.389.1002 Boehringer Ingelheim Investigational Site | Wien | Austria | ||
| 13 | 205.389.1006 Boehringer Ingelheim Investigational Site | Wien | Austria | ||
| 14 | 205.389.1014 Boehringer Ingelheim Investigational Site | Wien | Austria | ||
| 15 | 205.389.1018 Boehringer Ingelheim Investigational Site | Wien | Austria | ||
| 16 | 205.389.1021 Boehringer Ingelheim Investigational Site | Wien | Austria | ||
| 17 | 205.389.1029 Boehringer Ingelheim Investigational Site | Wien | Austria | ||
| 18 | 205.389.1017 Boehringer Ingelheim Investigational Site | Zwettl | Austria | ||
| 19 | 205.389.1120 Boehringer Ingelheim Investigational Site | Buizingen | Belgium | ||
| 20 | 205.389.1124 Boehringer Ingelheim Investigational Site | Cerexhe Heuseux | Belgium | ||
| 21 | 205.389.1116 Boehringer Ingelheim Investigational Site | Chenée (Liége) | Belgium | ||
| 22 | 205.389.1121 Boehringer Ingelheim Investigational Site | Dour | Belgium | ||
| 23 | 205.389.1113 Boehringer Ingelheim Investigational Site | Gembloux | Belgium | ||
| 24 | 205.389.1117 Boehringer Ingelheim Investigational Site | Gozée | Belgium | ||
| 25 | 205.389.1126 Boehringer Ingelheim Investigational Site | Hasselt | Belgium | ||
| 26 | 205.389.1129 Boehringer Ingelheim Investigational Site | Natoye | Belgium | ||
| 27 | 205.389.1130 Boehringer Ingelheim Investigational Site | Quaregnon | Belgium | ||
| 28 | 205.389.1115 Boehringer Ingelheim Investigational Site | Thuillies | Belgium | ||
| 29 | 205.389.1107 Boehringer Ingelheim Investigational Site | Wetteren | Belgium | ||
| 30 | 205.389.3911 Boehringer Ingelheim Investigational Site | Pazardjik | Bulgaria | ||
| 31 | 205.389.3903 Boehringer Ingelheim Investigational Site | Plovdiv | Bulgaria | ||
| 32 | 205.389.3915 Boehringer Ingelheim Investigational Site | Plovdiv | Bulgaria | ||
| 33 | 205.389.3918 Boehringer Ingelheim Investigational Site | Rousse | Bulgaria | ||
| 34 | 205.389.3914 Boehringer Ingelheim Investigational Site | Sliven | Bulgaria | ||
| 35 | 205.389.3902 Boehringer Ingelheim Investigational Site | Sofia | Bulgaria | ||
| 36 | 205.389.3906 Boehringer Ingelheim Investigational Site | Sofia | Bulgaria | ||
| 37 | 205.389.3907 Boehringer Ingelheim Investigational Site | Sofia | Bulgaria | ||
| 38 | 205.389.3908 Boehringer Ingelheim Investigational Site | Stara Zagora | Bulgaria | ||
| 39 | 205.389.3916 Boehringer Ingelheim Investigational Site | Troyan | Bulgaria | ||
| 40 | 205.389.3912 Boehringer Ingelheim Investigational Site | Varna | Bulgaria | ||
| 41 | 205.389.3901 Boehringer Ingelheim Investigational Site | Veliko Turnovo | Bulgaria | ||
| 42 | 205.389.1211 Boehringer Ingelheim Investigational Site | Benesov | Czech Republic | ||
| 43 | 205.389.1213 Boehringer Ingelheim Investigational Site | Beroun | Czech Republic | ||
| 44 | 205.389.1220 Boehringer Ingelheim Investigational Site | Beroun | Czech Republic | ||
| 45 | 205.389.1204 Boehringer Ingelheim Investigational Site | Brno-Kralovo Pole | Czech Republic | ||
| 46 | 205.389.1212 Boehringer Ingelheim Investigational Site | Cheb | Czech Republic | ||
| 47 | 205.389.1205 Boehringer Ingelheim Investigational Site | Havlickuv Brod | Czech Republic | ||
| 48 | 205.389.1230 Boehringer Ingelheim Investigational Site | Humpolec | Czech Republic | ||
| 49 | 205.389.1208 Boehringer Ingelheim Investigational Site | Jaromer | Czech Republic | ||
| 50 | 205.389.1219 Boehringer Ingelheim Investigational Site | Kyjov | Czech Republic | ||
| 51 | 205.389.1225 Boehringer Ingelheim Investigational Site | Liberec | Czech Republic | ||
| 52 | 205.389.1218 Boehringer Ingelheim Investigational Site | Litomerice | Czech Republic | ||
| 53 | 205.389.1214 Boehringer Ingelheim Investigational Site | Lovosice | Czech Republic | ||
| 54 | 205.389.1207 Boehringer Ingelheim Investigational Site | Neratovice | Czech Republic | ||
| 55 | 205.389.1222 Boehringer Ingelheim Investigational Site | Ostrava | Czech Republic | ||
| 56 | 205.389.1209 Boehringer Ingelheim Investigational Site | Plzen | Czech Republic | ||
| 57 | 205.389.1216 Boehringer Ingelheim Investigational Site | Plzen | Czech Republic | ||
| 58 | 205.389.1217 Boehringer Ingelheim Investigational Site | Praha 13 | Czech Republic | ||
| 59 | 205.389.1215 Boehringer Ingelheim Investigational Site | Praha 17 | Czech Republic | ||
| 60 | 205.389.1232 Boehringer Ingelheim Investigational Site | Praha 3 | Czech Republic | ||
| 61 | 205.389.1229 Boehringer Ingelheim Investigational Site | Praha 4 | Czech Republic | ||
| 62 | 205.389.1223 Boehringer Ingelheim Investigational Site | Praha 5 | Czech Republic | ||
| 63 | 205.389.1227 Boehringer Ingelheim Investigational Site | Praha 5 | Czech Republic | ||
| 64 | 205.389.1224 Boehringer Ingelheim Investigational Site | Praha 6 - Brevnov | Czech Republic | ||
| 65 | 205.389.1228 Boehringer Ingelheim Investigational Site | Prerov | Czech Republic | ||
| 66 | 205.389.1231 Boehringer Ingelheim Investigational Site | Rokycany | Czech Republic | ||
| 67 | 205.389.1221 Boehringer Ingelheim Investigational Site | Strakonice | Czech Republic | ||
| 68 | 205.389.1206 Boehringer Ingelheim Investigational Site | Tremosna | Czech Republic | ||
| 69 | 205.389.1201 Boehringer Ingelheim Investigational Site | Zatec | Czech Republic | ||
| 70 | 205.389.1210 Boehringer Ingelheim Investigational Site | Znojmo | Czech Republic | ||
| 71 | 205.389.1304 Boehringer Ingelheim Investigational Site | Copenhagen | Denmark | ||
| 72 | 205.389.1309 Boehringer Ingelheim Investigational Site | Frederikssund | Denmark | ||
| 73 | 205.389.1301 Boehringer Ingelheim Investigational Site | Helsingor | Denmark | ||
| 74 | 205.389.1308 Boehringer Ingelheim Investigational Site | Helsingør | Denmark | ||
| 75 | 205.389.1311 Boehringer Ingelheim Investigational Site | Holstebro | Denmark | ||
| 76 | 205.389.1302 Boehringer Ingelheim Investigational Site | Næstved | Denmark | ||
| 77 | 205.389.1303 Boehringer Ingelheim Investigational Site | Roskilde | Denmark | ||
| 78 | 205.389.1310 Boehringer Ingelheim Investigational Site | Skive | Denmark | ||
| 79 | 205.389.1312 Boehringer Ingelheim Investigational Site | Sonderborg | Denmark | ||
| 80 | 205.389.1307 Boehringer Ingelheim Investigational Site | Værløse | Denmark | ||
| 81 | 205.389.1402 Boehringer Ingelheim Investigational Site | Helsinki | Finland | ||
| 82 | 205.389.1416 Boehringer Ingelheim Investigational Site | Hyvinkää | Finland | ||
| 83 | 205.389.1410 Boehringer Ingelheim Investigational Site | Jyväskylä | Finland | ||
| 84 | 205.389.1404 Boehringer Ingelheim Investigational Site | Lahti | Finland | ||
| 85 | 205.389.1417 Boehringer Ingelheim Investigational Site | Lappeenranta | Finland | ||
| 86 | 205.389.1415 Boehringer Ingelheim Investigational Site | Lohja | Finland | ||
| 87 | 205.389.1411 Boehringer Ingelheim Investigational Site | Mikkeli | Finland | ||
| 88 | 205.389.1409 Boehringer Ingelheim Investigational Site | Pori | Finland | ||
| 89 | 205.389.1412 Boehringer Ingelheim Investigational Site | Preitilä Paimio | Finland | ||
| 90 | 205.389.1407 Boehringer Ingelheim Investigational Site | Turku | Finland | ||
| 91 | 205.389.1607 Boehringer Ingelheim Investigational Site | Bauge | France | ||
| 92 | 205.389.1525 Boehringer Ingelheim Investigational Site | Beauvais | France | ||
| 93 | 205.389.1523 Boehringer Ingelheim Investigational Site | Bethune | France | ||
| 94 | 205.389.1571 Boehringer Ingelheim Investigational Site | Cestas | France | ||
| 95 | 205.389.1561 Boehringer Ingelheim Investigational Site | Charry le Rouet | France | ||
| 96 | 205.389.1507 Boehringer Ingelheim Investigational Site | Cholet | France | ||
| 97 | 205.389.1606 Boehringer Ingelheim Investigational Site | Ecouflant | France | ||
| 98 | 205.389.1554 Boehringer Ingelheim Investigational Site | Ermont | France | ||
| 99 | 205.389.1597 Boehringer Ingelheim Investigational Site | La Barre de Monts | France | ||
| 100 | 205.389.1581 Boehringer Ingelheim Investigational Site | La Jubaudière | France | ||
| 101 | 205.389.1536 Boehringer Ingelheim Investigational Site | La Roche Sur Yon | France | ||
| 102 | 205.389.1598 Boehringer Ingelheim Investigational Site | La Roche sur Yon | France | ||
| 103 | 205.389.1501 Boehringer Ingelheim Investigational Site | Le Kremlin Bicetre | France | ||
| 104 | 205.389.1503 Boehringer Ingelheim Investigational Site | Le Mans Cedex | France | ||
| 105 | 205.389.1586 Boehringer Ingelheim Investigational Site | Le Pradet | France | ||
| 106 | 205.389.1528 Boehringer Ingelheim Investigational Site | Marseille | France | ||
| 107 | 205.389.1530 Boehringer Ingelheim Investigational Site | Marseille | France | ||
| 108 | 205.389.1558 Boehringer Ingelheim Investigational Site | Marseille | France | ||
| 109 | 205.389.1564 Boehringer Ingelheim Investigational Site | Marseille | France | ||
| 110 | 205.389.1565 Boehringer Ingelheim Investigational Site | Marseille | France | ||
| 111 | 205.389.1539 Boehringer Ingelheim Investigational Site | Montfermeil | France | ||
| 112 | 205.389.1608 Boehringer Ingelheim Investigational Site | Nantes | France | ||
| 113 | 205.389.1526 Boehringer Ingelheim Investigational Site | Nice | France | ||
| 114 | 205.389.1504 Boehringer Ingelheim Investigational Site | Nimes | France | ||
| 115 | 205.389.1502 Boehringer Ingelheim Investigational Site | Ollioules | France | ||
| 116 | 205.389.1541 Boehringer Ingelheim Investigational Site | Orleans | France | ||
| 117 | 205.389.1527 Boehringer Ingelheim Investigational Site | Perpignan | France | ||
| 118 | 205.389.1532 Boehringer Ingelheim Investigational Site | PIERRE BENITE cédex | France | ||
| 119 | 205.389.1553 Boehringer Ingelheim Investigational Site | Rennes cedex 9 | France | ||
| 120 | 205.389.1555 Boehringer Ingelheim Investigational Site | Saint Dié des Vosges | France | ||
| 121 | 205.389.1575 Boehringer Ingelheim Investigational Site | Saint Germain du Puch | France | ||
| 122 | 205.389.1547 Boehringer Ingelheim Investigational Site | Saint Laurent du Var | France | ||
| 123 | 205.389.1572 Boehringer Ingelheim Investigational Site | Saint Laurent | France | ||
| 124 | 205.389.1567 Boehringer Ingelheim Investigational Site | Saint Orens de Cameville | France | ||
| 125 | 205.389.1577 Boehringer Ingelheim Investigational Site | Saint Pierre Montlimard | France | ||
| 126 | 205.389.1531 Boehringer Ingelheim Investigational Site | Saint Quentin | France | ||
| 127 | 205.389.1569 Boehringer Ingelheim Investigational Site | Seysses | France | ||
| 128 | 205.389.1514 Boehringer Ingelheim Investigational Site | St-Etienne | France | ||
| 129 | 205.389.1510 Boehringer Ingelheim Investigational Site | Strasbourg | France | ||
| 130 | 205.389.1522 Boehringer Ingelheim Investigational Site | Strasbourg | France | ||
| 131 | 205.389.1520 Boehringer Ingelheim Investigational Site | Sélestat | France | ||
| 132 | 205.389.1512 Boehringer Ingelheim Investigational Site | Toulon | France | ||
| 133 | 205.389.1515 Boehringer Ingelheim Investigational Site | Toulon | France | ||
| 134 | 205.389.1519 Boehringer Ingelheim Investigational Site | Toulon | France | ||
| 135 | 205.389.1588 Boehringer Ingelheim Investigational Site | Toulon | France | ||
| 136 | 205.389.1589 Boehringer Ingelheim Investigational Site | Toulon | France | ||
| 137 | 205.389.1590 Boehringer Ingelheim Investigational Site | Toulon | France | ||
| 138 | 205.389.1595 Boehringer Ingelheim Investigational Site | Toulon | France | ||
| 139 | 205.389.1542 Boehringer Ingelheim Investigational Site | Toulouse | France | ||
| 140 | 205.389.1574 Boehringer Ingelheim Investigational Site | Villenave D'ornon | France | ||
| 141 | 205.389.1741 Boehringer Ingelheim Investigational Site | Aachen | Germany | ||
| 142 | 205.389.1857 Boehringer Ingelheim Investigational Site | Aalen | Germany | ||
| 143 | 205.389.1934 Boehringer Ingelheim Investigational Site | Auerbach | Germany | ||
| 144 | 205.389.1868 Boehringer Ingelheim Investigational Site | Augsburg | Germany | ||
| 145 | 205.389.1887 Boehringer Ingelheim Investigational Site | Augsburg | Germany | ||
| 146 | 205.389.1707 Boehringer Ingelheim Investigational Site | Bad Lippspringe | Germany | ||
| 147 | 205.389.1722 Boehringer Ingelheim Investigational Site | Bad Pymont | Germany | ||
| 148 | 205.389.1850 Boehringer Ingelheim Investigational Site | Bad Wörishofen | Germany | ||
| 149 | 205.389.1765 Boehringer Ingelheim Investigational Site | Bahrdorf | Germany | ||
| 150 | 205.389.1792 Boehringer Ingelheim Investigational Site | Beckum | Germany | ||
| 151 | 205.389.1801 Boehringer Ingelheim Investigational Site | Bensheim | Germany | ||
| 152 | 205.389.1946 Boehringer Ingelheim Investigational Site | Bensheim | Germany | ||
| 153 | 205.389.1824 Boehringer Ingelheim Investigational Site | Bergisch Gladbach | Germany | ||
| 154 | 205.389.1709 Boehringer Ingelheim Investigational Site | Bergkamen | Germany | ||
| 155 | 205.389.1750 Boehringer Ingelheim Investigational Site | Berkatal-Frankershausen | Germany | ||
| 156 | 205.389.1701 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 157 | 205.389.1743 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 158 | 205.389.1769 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 159 | 205.389.1789 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 160 | 205.389.1790 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 161 | 205.389.1847 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 162 | 205.389.1855 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 163 | 205.389.1861 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 164 | 205.389.1862 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 165 | 205.389.1867 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 166 | 205.389.1903 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 167 | 205.389.1931 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 168 | 205.389.1932 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 169 | 205.389.1937 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 170 | 205.389.1960 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 171 | 205.389.1969 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 172 | 205.389.1981 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 173 | 205.389.1983 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 174 | 205.389.1984 Boehringer Ingelheim Investigational Site | Berlin | Germany | ||
| 175 | 205.389.1747 Boehringer Ingelheim Investigational Site | Bocholt | Germany | ||
| 176 | 205.389.1808 Boehringer Ingelheim Investigational Site | Bochum | Germany | ||
| 177 | 205.389.1811 Boehringer Ingelheim Investigational Site | Bochum | Germany | ||
| 178 | 205.389.1828 Boehringer Ingelheim Investigational Site | Bonn | Germany | ||
| 179 | 205.389.1870 Boehringer Ingelheim Investigational Site | Bonn | Germany | ||
| 180 | 205.389.1705 Boehringer Ingelheim Investigational Site | Borna | Germany | ||
| 181 | 205.389.1809 Boehringer Ingelheim Investigational Site | Brandenburg/Havel | Germany | ||
| 182 | 205.389.1859 Boehringer Ingelheim Investigational Site | Bruchsal | Germany | ||
| 183 | 205.389.1734 Boehringer Ingelheim Investigational Site | Camburg | Germany | ||
| 184 | 205.389.1923 Boehringer Ingelheim Investigational Site | Celle | Germany | ||
| 185 | 205.389.1901 Boehringer Ingelheim Investigational Site | Coswig | Germany | ||
| 186 | 205.389.1891 Boehringer Ingelheim Investigational Site | Cottbus | Germany | ||
| 187 | 205.389.1858 Boehringer Ingelheim Investigational Site | Deggendorf | Germany | ||
| 188 | 205.389.1784 Boehringer Ingelheim Investigational Site | Donaueschingen | Germany | ||
| 189 | 205.389.1713 Boehringer Ingelheim Investigational Site | Dortmund | Germany | ||
| 190 | 205.389.1706 Boehringer Ingelheim Investigational Site | Dresden | Germany | ||
| 191 | 205.389.1967 Boehringer Ingelheim Investigational Site | Düren | Germany | ||
| 192 | 205.389.1814 Boehringer Ingelheim Investigational Site | Engelskirchen | Germany | ||
| 193 | 205.389.1773 Boehringer Ingelheim Investigational Site | Ense | Germany | ||
| 194 | 205.389.1727 Boehringer Ingelheim Investigational Site | Eppelborn-Bubach | Germany | ||
| 195 | 205.389.1864 Boehringer Ingelheim Investigational Site | Erfurt | Germany | ||
| 196 | 205.389.1940 Boehringer Ingelheim Investigational Site | Erlangen | Germany | ||
| 197 | 205.389.1900 Boehringer Ingelheim Investigational Site | Eschwege | Germany | ||
| 198 | 205.389.1758 Boehringer Ingelheim Investigational Site | Essen | Germany | ||
| 199 | 205.389.1975 Boehringer Ingelheim Investigational Site | Essen | Germany | ||
| 200 | 205.389.1982 Boehringer Ingelheim Investigational Site | Essen | Germany | ||
| 201 | 205.389.1724 Boehringer Ingelheim Investigational Site | Ettlingen | Germany | ||
| 202 | 205.389.1806 Boehringer Ingelheim Investigational Site | Feldkirchen-Westerham | Germany | ||
| 203 | 205.389.1976 Boehringer Ingelheim Investigational Site | Forchheim | Germany | ||
| 204 | 205.389.1795 Boehringer Ingelheim Investigational Site | Frankenberg | Germany | ||
| 205 | 205.389.1905 Boehringer Ingelheim Investigational Site | Frankfurt/Main | Germany | ||
| 206 | 205.389.1752 Boehringer Ingelheim Investigational Site | Fuldatal-Ihringshausen | Germany | ||
| 207 | 205.389.1943 Boehringer Ingelheim Investigational Site | Föhren | Germany | ||
| 208 | 205.389.1971 Boehringer Ingelheim Investigational Site | Fürth | Germany | ||
| 209 | 205.389.1766 Boehringer Ingelheim Investigational Site | Gars | Germany | ||
| 210 | 205.389.1977 Boehringer Ingelheim Investigational Site | Gelsenkirchen | Germany | ||
| 211 | 205.389.1744 Boehringer Ingelheim Investigational Site | Georgensgmünd | Germany | ||
| 212 | 205.389.1875 Boehringer Ingelheim Investigational Site | Gießen | Germany | ||
| 213 | 205.389.1836 Boehringer Ingelheim Investigational Site | Gifhorn | Germany | ||
| 214 | 205.389.1914 Boehringer Ingelheim Investigational Site | Goch | Germany | ||
| 215 | 205.389.1886 Boehringer Ingelheim Investigational Site | Greiz | Germany | ||
| 216 | 205.389.1768 Boehringer Ingelheim Investigational Site | Grünberg | Germany | ||
| 217 | 205.389.1751 Boehringer Ingelheim Investigational Site | Göttingen | Germany | ||
| 218 | 205.389.1831 Boehringer Ingelheim Investigational Site | Hagen | Germany | ||
| 219 | 205.389.1827 Boehringer Ingelheim Investigational Site | Halle | Germany | ||
| 220 | 205.389.1917 Boehringer Ingelheim Investigational Site | Hamburg | Germany | ||
| 221 | 205.389.1924 Boehringer Ingelheim Investigational Site | Hamburg | Germany | ||
| 222 | 205.389.1925 Boehringer Ingelheim Investigational Site | Hamburg | Germany | ||
| 223 | 205.389.1980 Boehringer Ingelheim Investigational Site | Hamburg | Germany | ||
| 224 | 205.389.1716 Boehringer Ingelheim Investigational Site | Hammah | Germany | ||
| 225 | 205.389.1702 Boehringer Ingelheim Investigational Site | Hammelburg | Germany | ||
| 226 | 205.389.1802 Boehringer Ingelheim Investigational Site | Hannover | Germany | ||
| 227 | 205.389.1712 Boehringer Ingelheim Investigational Site | Harsewinkel | Germany | ||
| 228 | 205.389.1738 Boehringer Ingelheim Investigational Site | Hauzenberg | Germany | ||
| 229 | 205.389.1860 Boehringer Ingelheim Investigational Site | Hemmingen | Germany | ||
| 230 | 205.389.1949 Boehringer Ingelheim Investigational Site | Höchstädt | Germany | ||
| 231 | 205.389.1726 Boehringer Ingelheim Investigational Site | Ingelheim | Germany | ||
| 232 | 205.389.1873 Boehringer Ingelheim Investigational Site | Karlsruhe | Germany | ||
| 233 | 205.389.1838 Boehringer Ingelheim Investigational Site | Kaufbeuren | Germany | ||
| 234 | 205.389.1839 Boehringer Ingelheim Investigational Site | Koblenz | Germany | ||
| 235 | 205.389.1881 Boehringer Ingelheim Investigational Site | Krefeld | Germany | ||
| 236 | 205.389.1786 Boehringer Ingelheim Investigational Site | Krumpa | Germany | ||
| 237 | 205.389.1704 Boehringer Ingelheim Investigational Site | Käbschütztal-Krögis | Germany | ||
| 238 | 205.389.1892 Boehringer Ingelheim Investigational Site | Köln | Germany | ||
| 239 | 205.389.1974 Boehringer Ingelheim Investigational Site | Köln | Germany | ||
| 240 | 205.389.1813 Boehringer Ingelheim Investigational Site | Köthen | Germany | ||
| 241 | 205.389.1902 Boehringer Ingelheim Investigational Site | Landsberg | Germany | ||
| 242 | 205.389.1837 Boehringer Ingelheim Investigational Site | Leipzig | Germany | ||
| 243 | 205.389.1841 Boehringer Ingelheim Investigational Site | Leipzig | Germany | ||
| 244 | 205.389.1894 Boehringer Ingelheim Investigational Site | Leipzig | Germany | ||
| 245 | 205.389.1908 Boehringer Ingelheim Investigational Site | Leipzig | Germany | ||
| 246 | 205.389.1874 Boehringer Ingelheim Investigational Site | Leonberg | Germany | ||
| 247 | 205.389.1955 Boehringer Ingelheim Investigational Site | Limburg | Germany | ||
| 248 | 205.389.1904 Boehringer Ingelheim Investigational Site | Lorch | Germany | ||
| 249 | 205.389.1877 Boehringer Ingelheim Investigational Site | Lübeck | Germany | ||
| 250 | 205.389.1823 Boehringer Ingelheim Investigational Site | Lützen | Germany | ||
| 251 | 205.389.1879 Boehringer Ingelheim Investigational Site | Magdeburg | Germany | ||
| 252 | 205.389.1840 Boehringer Ingelheim Investigational Site | Mannheim | Germany | ||
| 253 | 205.389.1978 Boehringer Ingelheim Investigational Site | Mannheim | Germany | ||
| 254 | 205.389.1866 Boehringer Ingelheim Investigational Site | Marburg | Germany | ||
| 255 | 205.389.1871 Boehringer Ingelheim Investigational Site | Marburg | Germany | ||
| 256 | 205.389.1926 Boehringer Ingelheim Investigational Site | Marburg | Germany | ||
| 257 | 205.389.1776 Boehringer Ingelheim Investigational Site | Marl | Germany | ||
| 258 | 205.389.1779 Boehringer Ingelheim Investigational Site | Merrbusch | Germany | ||
| 259 | 205.389.1799 Boehringer Ingelheim Investigational Site | München | Germany | ||
| 260 | 205.389.1815 Boehringer Ingelheim Investigational Site | München | Germany | ||
| 261 | 205.389.1817 Boehringer Ingelheim Investigational Site | München | Germany | ||
| 262 | 205.389.1843 Boehringer Ingelheim Investigational Site | München | Germany | ||
| 263 | 205.389.1952 Boehringer Ingelheim Investigational Site | Neubrandenburg | Germany | ||
| 264 | 205.389.1948 Boehringer Ingelheim Investigational Site | Neuss | Germany | ||
| 265 | 205.389.1958 Boehringer Ingelheim Investigational Site | Neuwied | Germany | ||
| 266 | 205.389.1805 Boehringer Ingelheim Investigational Site | Neuötting | Germany | ||
| 267 | 205.389.1830 Boehringer Ingelheim Investigational Site | Niesky | Germany | ||
| 268 | 205.389.1711 Boehringer Ingelheim Investigational Site | Nussbach | Germany | ||
| 269 | 205.389.1781 Boehringer Ingelheim Investigational Site | Oberdorla | Germany | ||
| 270 | 205.389.1753 Boehringer Ingelheim Investigational Site | Paderborn | Germany | ||
| 271 | 205.389.1810 Boehringer Ingelheim Investigational Site | Paderborn | Germany | ||
| 272 | 205.389.1854 Boehringer Ingelheim Investigational Site | Paderborn | Germany | ||
| 273 | 205.389.1756 Boehringer Ingelheim Investigational Site | Pirmasens | Germany | ||
| 274 | 205.389.1794 Boehringer Ingelheim Investigational Site | Potsdam | Germany | ||
| 275 | 205.389.1899 Boehringer Ingelheim Investigational Site | Potsdam | Germany | ||
| 276 | 205.389.1842 Boehringer Ingelheim Investigational Site | Radebeul | Germany | ||
| 277 | 205.389.1897 Boehringer Ingelheim Investigational Site | Rathenow | Germany | ||
| 278 | 205.389.1950 Boehringer Ingelheim Investigational Site | Raubach | Germany | ||
| 279 | 205.389.1783 Boehringer Ingelheim Investigational Site | Riesa | Germany | ||
| 280 | 205.389.1826 Boehringer Ingelheim Investigational Site | Riesa | Germany | ||
| 281 | 205.389.1742 Boehringer Ingelheim Investigational Site | Rostock | Germany | ||
| 282 | 205.389.1816 Boehringer Ingelheim Investigational Site | Rüdersdorf | Germany | ||
| 283 | 205.389.1883 Boehringer Ingelheim Investigational Site | Rüsselsheim | Germany | ||
| 284 | 205.389.1878 Boehringer Ingelheim Investigational Site | Saarlouis | Germany | ||
| 285 | 205.389.1833 Boehringer Ingelheim Investigational Site | Schmallenberg-Grafschaft | Germany | ||
| 286 | 205.389.1973 Boehringer Ingelheim Investigational Site | Schmölln | Germany | ||
| 287 | 205.389.1979 Boehringer Ingelheim Investigational Site | Schwetzingen | Germany | ||
| 288 | 205.389.1856 Boehringer Ingelheim Investigational Site | Simmern | Germany | ||
| 289 | 205.389.1918 Boehringer Ingelheim Investigational Site | Solingen | Germany | ||
| 290 | 205.389.1822 Boehringer Ingelheim Investigational Site | Steinfurt | Germany | ||
| 291 | 205.389.1728 Boehringer Ingelheim Investigational Site | Sulzbach | Germany | ||
| 292 | 205.389.1717 Boehringer Ingelheim Investigational Site | Templin | Germany | ||
| 293 | 205.389.1882 Boehringer Ingelheim Investigational Site | Treuenbrietzen | Germany | ||
| 294 | 205.389.1745 Boehringer Ingelheim Investigational Site | Wallerfing | Germany | ||
| 295 | 205.389.1800 Boehringer Ingelheim Investigational Site | Wardenburg | Germany | ||
| 296 | 205.389.1885 Boehringer Ingelheim Investigational Site | Weißenhorn | Germany | ||
| 297 | 205.389.1927 Boehringer Ingelheim Investigational Site | Westerstede | Germany | ||
| 298 | 205.389.1825 Boehringer Ingelheim Investigational Site | Weyhe | Germany | ||
| 299 | 205.389.1863 Boehringer Ingelheim Investigational Site | Wiesbaden | Germany | ||
| 300 | 205.389.1968 Boehringer Ingelheim Investigational Site | Wilhelmshaven | Germany | ||
| 301 | 205.389.1807 Boehringer Ingelheim Investigational Site | Wilster | Germany | ||
| 302 | 205.389.1754 Boehringer Ingelheim Investigational Site | Wolfsburg | Germany | ||
| 303 | 205.389.1919 Boehringer Ingelheim Investigational Site | Wuppertal | Germany | ||
| 304 | 205.389.1898 Boehringer Ingelheim Investigational Site | Zerbst | Germany | ||
| 305 | 205.389.2001 Boehringer Ingelheim Investigational Site | Budapest | Hungary | ||
| 306 | 205.389.2005 Boehringer Ingelheim Investigational Site | Budapest | Hungary | ||
| 307 | 205.389.2006 Boehringer Ingelheim Investigational Site | Budapest | Hungary | ||
| 308 | 205.389.2009 Boehringer Ingelheim Investigational Site | Budapest | Hungary | ||
| 309 | 205.389.2016 Boehringer Ingelheim Investigational Site | Budapest | Hungary | ||
| 310 | 205.389.2018 Boehringer Ingelheim Investigational Site | Budapest | Hungary | ||
| 311 | 205.389.2027 Boehringer Ingelheim Investigational Site | Budapest | Hungary | ||
| 312 | 205.389.2007 Boehringer Ingelheim Investigational Site | Debrecen | Hungary | ||
| 313 | 205.389.2035 Boehringer Ingelheim Investigational Site | Deszk | Hungary | ||
| 314 | 205.389.2015 Boehringer Ingelheim Investigational Site | Dunaújváros | Hungary | ||
| 315 | 205.389.2011 Boehringer Ingelheim Investigational Site | Füzesabony | Hungary | ||
| 316 | 205.389.2013 Boehringer Ingelheim Investigational Site | Gyor | Hungary | ||
| 317 | 205.389.2028 Boehringer Ingelheim Investigational Site | Gyula | Hungary | ||
| 318 | 205.389.2014 Boehringer Ingelheim Investigational Site | Jászberény | Hungary | ||
| 319 | 205.389.2021 Boehringer Ingelheim Investigational Site | Kecskemét | Hungary | ||
| 320 | 205.389.2025 Boehringer Ingelheim Investigational Site | Komárom | Hungary | ||
| 321 | 205.389.2024 Boehringer Ingelheim Investigational Site | Mosdós | Hungary | ||
| 322 | 205.389.2026 Boehringer Ingelheim Investigational Site | Mosonmagyaróvár | Hungary | ||
| 323 | 205.389.2031 Boehringer Ingelheim Investigational Site | Nyíregyháza | Hungary | ||
| 324 | 205.389.2002 Boehringer Ingelheim Investigational Site | Pécs | Hungary | ||
| 325 | 205.389.2017 Boehringer Ingelheim Investigational Site | Ráckeve | Hungary | ||
| 326 | 205.389.2003 Boehringer Ingelheim Investigational Site | Siófok | Hungary | ||
| 327 | 205.389.2010 Boehringer Ingelheim Investigational Site | Szarvas | Hungary | ||
| 328 | 205.389.2019 Boehringer Ingelheim Investigational Site | Szentendre | Hungary | ||
| 329 | 205.389.2022 Boehringer Ingelheim Investigational Site | Százhalombatta | Hungary | ||
| 330 | 205.389.2030 Boehringer Ingelheim Investigational Site | Tatabánya | Hungary | ||
| 331 | 205.389.2029 Boehringer Ingelheim Investigational Site | Törökbálint | Hungary | ||
| 332 | 205.389.2020 Boehringer Ingelheim Investigational Site | Veszprém | Hungary | ||
| 333 | 205.389.2008 Boehringer Ingelheim Investigational Site | Érd | Hungary | ||
| 334 | 205.389.2101 Boehringer Ingelheim Investigational Site | Afula | Israel | ||
| 335 | 205.389.2110 Boehringer Ingelheim Investigational Site | Ashkelon | Israel | ||
| 336 | 205.389.2106 Boehringer Ingelheim Investigational Site | Be'er-Sheva | Israel | ||
| 337 | 205.389.2112 Boehringer Ingelheim Investigational Site | Hadera | Israel | ||
| 338 | 205.389.2107 Boehringer Ingelheim Investigational Site | Haifa | Israel | ||
| 339 | 205.389.2111 Boehringer Ingelheim Investigational Site | Haifa | Israel | ||
| 340 | 205.389.2108 Boehringer Ingelheim Investigational Site | Holon | Israel | ||
| 341 | 205.389.2104 Boehringer Ingelheim Investigational Site | Jerusalem | Israel | ||
| 342 | 205.389.2114 Boehringer Ingelheim Investigational Site | Jerusalem | Israel | ||
| 343 | 205.389.2116 Boehringer Ingelheim Investigational Site | Nahariya | Israel | ||
| 344 | 205.389.2102 Boehringer Ingelheim Investigational Site | Petah Tiqwa | Israel | ||
| 345 | 205.389.2105 Boehringer Ingelheim Investigational Site | Rehovot | Israel | ||
| 346 | 205.389.2103 Boehringer Ingelheim Investigational Site | Tel Hashomer | Israel | ||
| 347 | 205.389.2117 Boehringer Ingelheim Investigational Site | Zerifin | Israel | ||
| 348 | 205.389.2211 Boehringer Ingelheim Investigational Site | Brescia | Italy | ||
| 349 | 205.389.2206 Boehringer Ingelheim Investigational Site | Cagliari | Italy | ||
| 350 | 205.389.2223 Boehringer Ingelheim Investigational Site | Catania | Italy | ||
| 351 | 205.389.2209 Boehringer Ingelheim Investigational Site | Ferrara | Italy | ||
| 352 | 205.389.2214 Boehringer Ingelheim Investigational Site | Genova | Italy | ||
| 353 | 205.389.2215 Boehringer Ingelheim Investigational Site | Lecco | Italy | ||
| 354 | 205.389.2221 Boehringer Ingelheim Investigational Site | Milano | Italy | ||
| 355 | 205.389.2226 Boehringer Ingelheim Investigational Site | Milano | Italy | ||
| 356 | 205.389.2224 Boehringer Ingelheim Investigational Site | Modena | Italy | ||
| 357 | 205.389.2203 Boehringer Ingelheim Investigational Site | Montescano (PV) | Italy | ||
| 358 | 205.389.2230 Boehringer Ingelheim Investigational Site | Napoli | Italy | ||
| 359 | 205.389.2201 Boehringer Ingelheim Investigational Site | Novara | Italy | ||
| 360 | 205.389.2229 Boehringer Ingelheim Investigational Site | Pavia | Italy | ||
| 361 | 205.389.2227 Boehringer Ingelheim Investigational Site | Pisa | Italy | ||
| 362 | 205.389.2205 Boehringer Ingelheim Investigational Site | Roma | Italy | ||
| 363 | 205.389.2228 Boehringer Ingelheim Investigational Site | Roma | Italy | ||
| 364 | 205.389.2210 Boehringer Ingelheim Investigational Site | Sassari | Italy | ||
| 365 | 205.389.2232 Boehringer Ingelheim Investigational Site | Treviso | Italy | ||
| 366 | 205.389.2315 Boehringer Ingelheim Investigational Site | Balvi | Latvia | ||
| 367 | 205.389.2305 Boehringer Ingelheim Investigational Site | Daugavpils | Latvia | ||
| 368 | 205.389.2313 Boehringer Ingelheim Investigational Site | Jelgava | Latvia | ||
| 369 | 205.389.2311 Boehringer Ingelheim Investigational Site | Kraslava | Latvia | ||
| 370 | 205.389.2312 Boehringer Ingelheim Investigational Site | Kuldiga | Latvia | ||
| 371 | 205.389.2301 Boehringer Ingelheim Investigational Site | Riga | Latvia | ||
| 372 | 205.389.2303 Boehringer Ingelheim Investigational Site | Riga | Latvia | ||
| 373 | 205.389.2307 Boehringer Ingelheim Investigational Site | Riga | Latvia | ||
| 374 | 205.389.2310 Boehringer Ingelheim Investigational Site | Riga | Latvia | ||
| 375 | 205.389.2306 Boehringer Ingelheim Investigational Site | Talsi | Latvia | ||
| 376 | 205.389.2314 Boehringer Ingelheim Investigational Site | Tukums | Latvia | ||
| 377 | 205.389.2304 Boehringer Ingelheim Investigational Site | Valmiera | Latvia | ||
| 378 | 205.389.2302 Boehringer Ingelheim Investigational Site | Ventspils | Latvia | ||
| 379 | 205.389.2401 Boehringer Ingelheim Investigational Site | Alytus | Lithuania | ||
| 380 | 205.389.2402 Boehringer Ingelheim Investigational Site | Kaunas | Lithuania | ||
| 381 | 205.389.2403 Boehringer Ingelheim Investigational Site | Kaunas | Lithuania | ||
| 382 | 205.389.2404 Boehringer Ingelheim Investigational Site | Kaunas | Lithuania | ||
| 383 | 205.389.2406 Boehringer Ingelheim Investigational Site | Kaunas | Lithuania | ||
| 384 | 205.389.2409 Boehringer Ingelheim Investigational Site | Kaunas | Lithuania | ||
| 385 | 205.389.2407 Boehringer Ingelheim Investigational Site | Klaipeda | Lithuania | ||
| 386 | 205.389.2411 Boehringer Ingelheim Investigational Site | Klaipeda | Lithuania | ||
| 387 | 205.389.2408 Boehringer Ingelheim Investigational Site | Siauliai | Lithuania | ||
| 388 | 205.389.2410 Boehringer Ingelheim Investigational Site | Utena | Lithuania | ||
| 389 | 205.389.2405 Boehringer Ingelheim Investigational Site | Vilnius | Lithuania | ||
| 390 | 205.389.2412 Boehringer Ingelheim Investigational Site | Vilnius | Lithuania | ||
| 391 | 205.389.2413 Boehringer Ingelheim Investigational Site | Vilnius | Lithuania | ||
| 392 | 205.389.2414 Boehringer Ingelheim Investigational Site | Vilnius | Lithuania | ||
| 393 | 205.389.2504 Boehringer Ingelheim Investigational Site | Rotterdam | Netherlands | ||
| 394 | 205.389.2508 Boehringer Ingelheim Investigational Site | te Leiderdrop | Netherlands | ||
| 395 | 205.389.2510 Boehringer Ingelheim Investigational Site | Velp | Netherlands | ||
| 396 | 205.389.2511 Boehringer Ingelheim Investigational Site | Zoetermeer | Netherlands | ||
| 397 | 205.389.2614 Boehringer Ingelheim Investigational Site | Alesund | Norway | ||
| 398 | 205.389.2604 Boehringer Ingelheim Investigational Site | Bekkestua | Norway | ||
| 399 | 205.389.2601 Boehringer Ingelheim Investigational Site | Elverum | Norway | ||
| 400 | 205.389.2611 Boehringer Ingelheim Investigational Site | Follebu | Norway | ||
| 401 | 205.389.2602 Boehringer Ingelheim Investigational Site | Hamar | Norway | ||
| 402 | 205.389.2610 Boehringer Ingelheim Investigational Site | Harstad | Norway | ||
| 403 | 205.389.2613 Boehringer Ingelheim Investigational Site | Harstad | Norway | ||
| 404 | 205.389.2609 Boehringer Ingelheim Investigational Site | Hønefoss | Norway | ||
| 405 | 205.389.2608 Boehringer Ingelheim Investigational Site | Lørenskog | Norway | ||
| 406 | 205.389.2605 Boehringer Ingelheim Investigational Site | Oslo | Norway | ||
| 407 | 205.389.2612 Boehringer Ingelheim Investigational Site | Oslo | Norway | ||
| 408 | 205.389.2616 Boehringer Ingelheim Investigational Site | Stavanger | Norway | ||
| 409 | 205.389.2708 Boehringer Ingelheim Investigational Site | Bialystok | Poland | ||
| 410 | 205.389.2744 Boehringer Ingelheim Investigational Site | Bialystok | Poland | ||
| 411 | 205.389.2762 Boehringer Ingelheim Investigational Site | Bialystok | Poland | ||
| 412 | 205.389.2765 Boehringer Ingelheim Investigational Site | Bialystok | Poland | ||
| 413 | 205.389.2778 Boehringer Ingelheim Investigational Site | Bielsko-Biala | Poland | ||
| 414 | 205.389.2706 Boehringer Ingelheim Investigational Site | Bienkowka 410 | Poland | ||
| 415 | 205.389.2750 Boehringer Ingelheim Investigational Site | Brzesko | Poland | ||
| 416 | 205.389.2758 Boehringer Ingelheim Investigational Site | Bydgoszcz | Poland | ||
| 417 | 205.389.2773 Boehringer Ingelheim Investigational Site | Bystra | Poland | ||
| 418 | 205.389.2800 Boehringer Ingelheim Investigational Site | Chodziez | Poland | ||
| 419 | 205.389.2712 Boehringer Ingelheim Investigational Site | Czestochowa | Poland | ||
| 420 | 205.389.2774 Boehringer Ingelheim Investigational Site | Czestochowa | Poland | ||
| 421 | 205.389.2815 Boehringer Ingelheim Investigational Site | Dzialdowo | Poland | ||
| 422 | 205.389.2787 Boehringer Ingelheim Investigational Site | Elblag | Poland | ||
| 423 | 205.389.2715 Boehringer Ingelheim Investigational Site | Gdansk | Poland | ||
| 424 | 205.389.2723 Boehringer Ingelheim Investigational Site | Gdansk | Poland | ||
| 425 | 205.389.2743 Boehringer Ingelheim Investigational Site | Gdansk | Poland | ||
| 426 | 205.389.2764 Boehringer Ingelheim Investigational Site | Gdansk | Poland | ||
| 427 | 205.389.2802 Boehringer Ingelheim Investigational Site | Gdansk | Poland | ||
| 428 | 205.389.2801 Boehringer Ingelheim Investigational Site | Gorzow Wlkp | Poland | ||
| 429 | 205.389.2805 Boehringer Ingelheim Investigational Site | Ilawa | Poland | ||
| 430 | 205.389.2791 Boehringer Ingelheim Investigational Site | Inowroclaw | Poland | ||
| 431 | 205.389.2705 Boehringer Ingelheim Investigational Site | Katowice | Poland | ||
| 432 | 205.389.2749 Boehringer Ingelheim Investigational Site | Katowice | Poland | ||
| 433 | 205.389.2771 Boehringer Ingelheim Investigational Site | Katowice | Poland | ||
| 434 | 205.389.2759 Boehringer Ingelheim Investigational Site | Koszalin | Poland | ||
| 435 | 205.389.2711 Boehringer Ingelheim Investigational Site | Krakow | Poland | ||
| 436 | 205.389.2722 Boehringer Ingelheim Investigational Site | Krakow | Poland | ||
| 437 | 205.389.2747 Boehringer Ingelheim Investigational Site | Krakow | Poland | ||
| 438 | 205.389.2753 Boehringer Ingelheim Investigational Site | Krakow | Poland | ||
| 439 | 205.389.2798 Boehringer Ingelheim Investigational Site | Krakow | Poland | ||
| 440 | 205.389.2748 Boehringer Ingelheim Investigational Site | Kraków | Poland | ||
| 441 | 205.389.2757 Boehringer Ingelheim Investigational Site | Kutno | Poland | ||
| 442 | 205.389.2727 Boehringer Ingelheim Investigational Site | Leszno | Poland | ||
| 443 | 205.389.2701 Boehringer Ingelheim Investigational Site | Lodz | Poland | ||
| 444 | 205.389.2709 Boehringer Ingelheim Investigational Site | Lodz | Poland | ||
| 445 | 205.389.2716 Boehringer Ingelheim Investigational Site | Lodz | Poland | ||
| 446 | 205.389.2724 Boehringer Ingelheim Investigational Site | Lodz | Poland | ||
| 447 | 205.389.2732 Boehringer Ingelheim Investigational Site | Lodz | Poland | ||
| 448 | 205.389.2746 Boehringer Ingelheim Investigational Site | Lodz | Poland | ||
| 449 | 205.389.2751 Boehringer Ingelheim Investigational Site | Lodz | Poland | ||
| 450 | 205.389.2804 Boehringer Ingelheim Investigational Site | Lomza | Poland | ||
| 451 | 205.389.2741 Boehringer Ingelheim Investigational Site | Lublin | Poland | ||
| 452 | 205.389.2776 Boehringer Ingelheim Investigational Site | Lublin | Poland | ||
| 453 | 205.389.2817 Boehringer Ingelheim Investigational Site | Lublin | Poland | ||
| 454 | 205.389.2760 Boehringer Ingelheim Investigational Site | Olawa | Poland | ||
| 455 | 205.389.2756 Boehringer Ingelheim Investigational Site | Olsztyn | Poland | ||
| 456 | 205.389.2816 Boehringer Ingelheim Investigational Site | Olsztyn | Poland | ||
| 457 | 205.389.2702 Boehringer Ingelheim Investigational Site | Ostrow Wielkopolska | Poland | ||
| 458 | 205.389.2726 Boehringer Ingelheim Investigational Site | Pabianice | Poland | ||
| 459 | 205.389.2795 Boehringer Ingelheim Investigational Site | Plawno | Poland | ||
| 460 | 205.389.2730 Boehringer Ingelheim Investigational Site | Plock | Poland | ||
| 461 | 205.389.2703 Boehringer Ingelheim Investigational Site | Poznan | Poland | ||
| 462 | 205.389.2719 Boehringer Ingelheim Investigational Site | Poznan | Poland | ||
| 463 | 205.389.2737 Boehringer Ingelheim Investigational Site | Poznan | Poland | ||
| 464 | 205.389.2766 Boehringer Ingelheim Investigational Site | Poznan | Poland | ||
| 465 | 205.389.2769 Boehringer Ingelheim Investigational Site | Poznan | Poland | ||
| 466 | 205.389.2813 Boehringer Ingelheim Investigational Site | Poznan | Poland | ||
| 467 | 205.389.2763 Boehringer Ingelheim Investigational Site | Proszowice | Poland | ||
| 468 | 205.389.2767 Boehringer Ingelheim Investigational Site | Pruszkow | Poland | ||
| 469 | 205.389.2768 Boehringer Ingelheim Investigational Site | Radom | Poland | ||
| 470 | 205.389.2792 Boehringer Ingelheim Investigational Site | Sandomierz | Poland | ||
| 471 | 205.389.2781 Boehringer Ingelheim Investigational Site | Sieradz | Poland | ||
| 472 | 205.389.2725 Boehringer Ingelheim Investigational Site | Skierniewice | Poland | ||
| 473 | 205.389.2777 Boehringer Ingelheim Investigational Site | Szczecin - Zdunowo | Poland | ||
| 474 | 205.389.2782 Boehringer Ingelheim Investigational Site | Szczecin - Zdunowo | Poland | ||
| 475 | 205.389.2718 Boehringer Ingelheim Investigational Site | Szczecin | Poland | ||
| 476 | 205.389.2739 Boehringer Ingelheim Investigational Site | Szczecin | Poland | ||
| 477 | 205.389.2772 Boehringer Ingelheim Investigational Site | Szczecin | Poland | ||
| 478 | 205.389.2738 Boehringer Ingelheim Investigational Site | Tarnow | Poland | ||
| 479 | 205.389.2799 Boehringer Ingelheim Investigational Site | Tarnow | Poland | ||
| 480 | 205.389.2810 Boehringer Ingelheim Investigational Site | Tczew | Poland | ||
| 481 | 205.389.2775 Boehringer Ingelheim Investigational Site | Torun | Poland | ||
| 482 | 205.389.2754 Boehringer Ingelheim Investigational Site | Tranow | Poland | ||
| 483 | 205.389.2806 Boehringer Ingelheim Investigational Site | Turek | Poland | ||
| 484 | 205.389.2803 Boehringer Ingelheim Investigational Site | Wabrzenzo | Poland | ||
| 485 | 205.389.2707 Boehringer Ingelheim Investigational Site | Warsaw | Poland | ||
| 486 | 205.389.2714 Boehringer Ingelheim Investigational Site | Warsaw | Poland | ||
| 487 | 205.389.2728 Boehringer Ingelheim Investigational Site | Warsaw | Poland | ||
| 488 | 205.389.2734 Boehringer Ingelheim Investigational Site | Warszawa | Poland | ||
| 489 | 205.389.2812 Boehringer Ingelheim Investigational Site | Warszawa | Poland | ||
| 490 | 205.389.2818 Boehringer Ingelheim Investigational Site | Warszawa | Poland | ||
| 491 | 205.389.2710 Boehringer Ingelheim Investigational Site | Wodzislaw Slaski | Poland | ||
| 492 | 205.389.2721 Boehringer Ingelheim Investigational Site | Wroclaw | Poland | ||
| 493 | 205.389.2731 Boehringer Ingelheim Investigational Site | Wroclaw | Poland | ||
| 494 | 205.389.2736 Boehringer Ingelheim Investigational Site | Wroclaw | Poland | ||
| 495 | 205.389.2752 Boehringer Ingelheim Investigational Site | Wroclaw | Poland | ||
| 496 | 205.389.2761 Boehringer Ingelheim Investigational Site | Wroclaw | Poland | ||
| 497 | 205.389.2780 Boehringer Ingelheim Investigational Site | Wroclaw | Poland | ||
| 498 | 205.389.2793 Boehringer Ingelheim Investigational Site | Wroclaw | Poland | ||
| 499 | 205.389.2783 Boehringer Ingelheim Investigational Site | Zabrze | Poland | ||
| 500 | 205.389.2735 Boehringer Ingelheim Investigational Site | Zakopane | Poland | ||
| 501 | 205.389.2770 Boehringer Ingelheim Investigational Site | Zgierz | Poland | ||
| 502 | 205.389.2912 Boehringer Ingelheim Investigational Site | Angra do Heroísmo | Portugal | ||
| 503 | 205.389.2911 Boehringer Ingelheim Investigational Site | Barreiro | Portugal | ||
| 504 | 205.389.2904 Boehringer Ingelheim Investigational Site | Faro | Portugal | ||
| 505 | 205.389.2910 Boehringer Ingelheim Investigational Site | Figueira da Foz | Portugal | ||
| 506 | 205.389.2907 Boehringer Ingelheim Investigational Site | Guarda | Portugal | ||
| 507 | 205.389.2914 Boehringer Ingelheim Investigational Site | Lisboa | Portugal | ||
| 508 | 205.389.2917 Boehringer Ingelheim Investigational Site | Lisboa | Portugal | ||
| 509 | 205.389.2905 Boehringer Ingelheim Investigational Site | Santa Maria da Feira | Portugal | ||
| 510 | 205.389.2909 Boehringer Ingelheim Investigational Site | Santiago do Cacem | Portugal | ||
| 511 | 205.389.2903 Boehringer Ingelheim Investigational Site | Torres Vedras | Portugal | ||
| 512 | 205.389.3009 Boehringer Ingelheim Investigational Site | Brasov | Romania | ||
| 513 | 205.389.3018 Boehringer Ingelheim Investigational Site | Brasov | Romania | ||
| 514 | 205.389.3023 Boehringer Ingelheim Investigational Site | Brasov | Romania | ||
| 515 | 205.389.3025 Boehringer Ingelheim Investigational Site | Bucharest | Romania | ||
| 516 | 205.389.3001 Boehringer Ingelheim Investigational Site | Bucuresti | Romania | ||
| 517 | 205.389.3002 Boehringer Ingelheim Investigational Site | Bucuresti | Romania | ||
| 518 | 205.389.3004 Boehringer Ingelheim Investigational Site | Bucuresti | Romania | ||
| 519 | 205.389.3006 Boehringer Ingelheim Investigational Site | Bucuresti | Romania | ||
| 520 | 205.389.3007 Boehringer Ingelheim Investigational Site | Bucuresti | Romania | ||
| 521 | 205.389.3012 Boehringer Ingelheim Investigational Site | Bucuresti | Romania | ||
| 522 | 205.389.3013 Boehringer Ingelheim Investigational Site | Bucuresti | Romania | ||
| 523 | 205.389.3016 Boehringer Ingelheim Investigational Site | Constanta | Romania | ||
| 524 | 205.389.3019 Boehringer Ingelheim Investigational Site | Constanta | Romania | ||
| 525 | 205.389.3015 Boehringer Ingelheim Investigational Site | Craiova | Romania | ||
| 526 | 205.389.3008 Boehringer Ingelheim Investigational Site | Iasi | Romania | ||
| 527 | 205.389.3014 Boehringer Ingelheim Investigational Site | Iasi | Romania | ||
| 528 | 205.389.3022 Boehringer Ingelheim Investigational Site | Iasi | Romania | ||
| 529 | 205.389.3024 Boehringer Ingelheim Investigational Site | Iasi | Romania | ||
| 530 | 205.389.3005 Boehringer Ingelheim Investigational Site | Oradea | Romania | ||
| 531 | 205.389.3017 Boehringer Ingelheim Investigational Site | Tg. Mures | Romania | ||
| 532 | 205.389.3021 Boehringer Ingelheim Investigational Site | Timisoara | Romania | ||
| 533 | 205.389.3174 Boehringer Ingelheim Investigational Site | Arkhangelsk | Russian Federation | ||
| 534 | 205.389.3113 Boehringer Ingelheim Investigational Site | Barnaul | Russian Federation | ||
| 535 | 205.389.3131 Boehringer Ingelheim Investigational Site | Barnaul | Russian Federation | ||
| 536 | 205.389.3105 Boehringer Ingelheim Investigational Site | Chelyabinsk | Russian Federation | ||
| 537 | 205.389.3182 Boehringer Ingelheim Investigational Site | Chelyabinsk | Russian Federation | ||
| 538 | 205.389.3183 Boehringer Ingelheim Investigational Site | Chelyabinsk | Russian Federation | ||
| 539 | 205.389.3184 Boehringer Ingelheim Investigational Site | Chelyabinsk | Russian Federation | ||
| 540 | 205.389.3116 Boehringer Ingelheim Investigational Site | Ekaterinburg | Russian Federation | ||
| 541 | 205.389.3138 Boehringer Ingelheim Investigational Site | Ekaterinburg | Russian Federation | ||
| 542 | 205.389.3148 Boehringer Ingelheim Investigational Site | Ekaterinburg | Russian Federation | ||
| 543 | 205.389.3166 Boehringer Ingelheim Investigational Site | Ekaterinburg | Russian Federation | ||
| 544 | 205.389.3186 Boehringer Ingelheim Investigational Site | Gatchina (Leningradskaya oblast) | Russian Federation | ||
| 545 | 205.389.3193 Boehringer Ingelheim Investigational Site | Kaliningrad | Russian Federation | ||
| 546 | 205.389.3104 Boehringer Ingelheim Investigational Site | Kazan | Russian Federation | ||
| 547 | 205.389.3111 Boehringer Ingelheim Investigational Site | Kemerovo | Russian Federation | ||
| 548 | 205.389.3120 Boehringer Ingelheim Investigational Site | Kirov | Russian Federation | ||
| 549 | 205.389.3170 Boehringer Ingelheim Investigational Site | Krasnodar | Russian Federation | ||
| 550 | 205.389.3132 Boehringer Ingelheim Investigational Site | Krasnoyarsk | Russian Federation | ||
| 551 | 205.389.3103 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 552 | 205.389.3106 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 553 | 205.389.3107 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 554 | 205.389.3108 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 555 | 205.389.3109 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 556 | 205.389.3125 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 557 | 205.389.3127 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 558 | 205.389.3128 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 559 | 205.389.3130 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 560 | 205.389.3134 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 561 | 205.389.3136 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 562 | 205.389.3139 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 563 | 205.389.3140 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 564 | 205.389.3143 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 565 | 205.389.3149 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 566 | 205.389.3151 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 567 | 205.389.3156 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 568 | 205.389.3157 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 569 | 205.389.3163 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 570 | 205.389.3164 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 571 | 205.389.3167 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 572 | 205.389.3168 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 573 | 205.389.3171 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 574 | 205.389.3196 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 575 | 205.389.3188 Boehringer Ingelheim Investigational Site | Murmansk | Russian Federation | ||
| 576 | 205.389.3953 Boehringer Ingelheim Investigational Site | Nizhniy Novgorod | Russian Federation | ||
| 577 | 205.389.3169 Boehringer Ingelheim Investigational Site | Nizhny Novgorod | Russian Federation | ||
| 578 | 205.389.3112 Boehringer Ingelheim Investigational Site | Novosibirsk | Russian Federation | ||
| 579 | 205.389.3114 Boehringer Ingelheim Investigational Site | Novosibirsk | Russian Federation | ||
| 580 | 205.389.3129 Boehringer Ingelheim Investigational Site | Novosibirsk | Russian Federation | ||
| 581 | 205.389.3141 Boehringer Ingelheim Investigational Site | Novosibirsk | Russian Federation | ||
| 582 | 205.389.3153 Boehringer Ingelheim Investigational Site | Novosibirsk | Russian Federation | ||
| 583 | 205.389.3175 Boehringer Ingelheim Investigational Site | Novosibirsk | Russian Federation | ||
| 584 | 205.389.3126 Boehringer Ingelheim Investigational Site | Orenburg | Russian Federation | ||
| 585 | 205.389.3185 Boehringer Ingelheim Investigational Site | Perm | Russian Federation | ||
| 586 | 205.389.3192 Boehringer Ingelheim Investigational Site | Petrozavodsk | Russian Federation | ||
| 587 | 205.389.3179 Boehringer Ingelheim Investigational Site | Pskov | Russian Federation | ||
| 588 | 205.389.3190 Boehringer Ingelheim Investigational Site | Pskov | Russian Federation | ||
| 589 | 205.389.3199 Boehringer Ingelheim Investigational Site | Pyatigorsk, | Russian Federation | ||
| 590 | 205.389.3159 Boehringer Ingelheim Investigational Site | Rostov-on-Don | Russian Federation | ||
| 591 | 205.389.3197 Boehringer Ingelheim Investigational Site | Ryazan | Russian Federation | ||
| 592 | 205.389.3198 Boehringer Ingelheim Investigational Site | Saint Petersburg | Russian Federation | ||
| 593 | 205.389.3110 Boehringer Ingelheim Investigational Site | Saratov | Russian Federation | ||
| 594 | 205.389.3951 Boehringer Ingelheim Investigational Site | Saratov | Russian Federation | ||
| 595 | 205.389.3191 Boehringer Ingelheim Investigational Site | St-Petersburg | Russian Federation | ||
| 596 | 205.389.3119 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 597 | 205.389.3121 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 598 | 205.389.3122 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 599 | 205.389.3123 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 600 | 205.389.3135 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 601 | 205.389.3137 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 602 | 205.389.3145 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 603 | 205.389.3146 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 604 | 205.389.3160 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 605 | 205.389.3161 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 606 | 205.389.3176 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 607 | 205.389.3177 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 608 | 205.389.3178 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 609 | 205.389.3180 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 610 | 205.389.3181 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 611 | 205.389.3189 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 612 | 205.389.3195 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 613 | 205.389.3950 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 614 | 205.389.3165 Boehringer Ingelheim Investigational Site | St.Peterburg | Russian Federation | ||
| 615 | 205.389.3117 Boehringer Ingelheim Investigational Site | St.Petersburg | Russian Federation | ||
| 616 | 205.389.3147 Boehringer Ingelheim Investigational Site | St.Petersburg | Russian Federation | ||
| 617 | 205.389.3152 Boehringer Ingelheim Investigational Site | St.Petersburg | Russian Federation | ||
| 618 | 205.389.3101 Boehringer Ingelheim Investigational Site | Tomsk | Russian Federation | ||
| 619 | 205.389.3102 Boehringer Ingelheim Investigational Site | Tomsk | Russian Federation | ||
| 620 | 205.389.3133 Boehringer Ingelheim Investigational Site | Tomsk | Russian Federation | ||
| 621 | 205.389.3144 Boehringer Ingelheim Investigational Site | Tomsk | Russian Federation | ||
| 622 | 205.389.3194 Boehringer Ingelheim Investigational Site | Velikiy Novgorod | Russian Federation | ||
| 623 | 205.389.3118 Boehringer Ingelheim Investigational Site | Yaroslavl | Russian Federation | ||
| 624 | 205.389.3155 Boehringer Ingelheim Investigational Site | Yaroslavl | Russian Federation | ||
| 625 | 205.389.3208 Boehringer Ingelheim Investigational Site | Bratislava | Slovakia | ||
| 626 | 205.389.3204 Boehringer Ingelheim Investigational Site | Kosice | Slovakia | ||
| 627 | 205.389.3209 Boehringer Ingelheim Investigational Site | Kosice | Slovakia | ||
| 628 | 205.389.3205 Boehringer Ingelheim Investigational Site | Prievidza | Slovakia | ||
| 629 | 205.389.3210 Boehringer Ingelheim Investigational Site | Revuca | Slovakia | ||
| 630 | 205.389.3203 Boehringer Ingelheim Investigational Site | Spisska Nova Ves | Slovakia | ||
| 631 | 205.389.3202 Boehringer Ingelheim Investigational Site | Trnava | Slovakia | ||
| 632 | 205.389.3207 Boehringer Ingelheim Investigational Site | Vrable | Slovakia | ||
| 633 | 205.389.3301 Boehringer Ingelheim Investigational Site | Golnik | Slovenia | ||
| 634 | 205.389.3308 Boehringer Ingelheim Investigational Site | Grosuplje | Slovenia | ||
| 635 | 205.389.3304 Boehringer Ingelheim Investigational Site | Jesenice | Slovenia | ||
| 636 | 205.389.3302 Boehringer Ingelheim Investigational Site | Kamnik | Slovenia | ||
| 637 | 205.389.3303 Boehringer Ingelheim Investigational Site | Ljubljana | Slovenia | ||
| 638 | 205.389.3306 Boehringer Ingelheim Investigational Site | Topolsica | Slovenia | ||
| 639 | 205.389.3410 Boehringer Ingelheim Investigational Site | Badajoz | Spain | ||
| 640 | 205.389.3403 Boehringer Ingelheim Investigational Site | Badalona (Barcelona) | Spain | ||
| 641 | 205.389.3401 Boehringer Ingelheim Investigational Site | Barcelona | Spain | ||
| 642 | 205.389.3402 Boehringer Ingelheim Investigational Site | Barcelona | Spain | ||
| 643 | 205.389.3428 Boehringer Ingelheim Investigational Site | Barcelona | Spain | ||
| 644 | 205.389.3430 Boehringer Ingelheim Investigational Site | Cartagena | Spain | ||
| 645 | 205.389.3416 Boehringer Ingelheim Investigational Site | Cáceres | Spain | ||
| 646 | 205.389.3425 Boehringer Ingelheim Investigational Site | Elche | Spain | ||
| 647 | 205.389.3408 Boehringer Ingelheim Investigational Site | Las Palmas de Gran Canarias | Spain | ||
| 648 | 205.389.3405 Boehringer Ingelheim Investigational Site | Lleida | Spain | ||
| 649 | 205.389.3404 Boehringer Ingelheim Investigational Site | Madrid | Spain | ||
| 650 | 205.389.3406 Boehringer Ingelheim Investigational Site | Madrid | Spain | ||
| 651 | 205.389.3414 Boehringer Ingelheim Investigational Site | Málaga | Spain | ||
| 652 | 205.389.3431 Boehringer Ingelheim Investigational Site | Pontevedra | Spain | ||
| 653 | 205.389.3419 Boehringer Ingelheim Investigational Site | Requena | Spain | ||
| 654 | 205.389.3427 Boehringer Ingelheim Investigational Site | Reus | Spain | ||
| 655 | 205.389.3422 Boehringer Ingelheim Investigational Site | Sagunto | Spain | ||
| 656 | 205.389.3420 Boehringer Ingelheim Investigational Site | San Juan | Spain | ||
| 657 | 205.389.3415 Boehringer Ingelheim Investigational Site | Santander | Spain | ||
| 658 | 205.389.3421 Boehringer Ingelheim Investigational Site | Santiago de Compostela | Spain | ||
| 659 | 205.389.3407 Boehringer Ingelheim Investigational Site | Terrasa (Barcelona) | Spain | ||
| 660 | 205.389.3413 Boehringer Ingelheim Investigational Site | Valencia | Spain | ||
| 661 | 205.389.3426 Boehringer Ingelheim Investigational Site | Valencia | Spain | ||
| 662 | 205.389.3417 Boehringer Ingelheim Investigational Site | Valladolid | Spain | ||
| 663 | 205.389.3821 Boehringer Ingelheim Investigational Site | Adana | Turkey | ||
| 664 | 205.389.3808 Boehringer Ingelheim Investigational Site | Ankara | Turkey | ||
| 665 | 205.389.3810 Boehringer Ingelheim Investigational Site | Ankara | Turkey | ||
| 666 | 205.389.3817 Boehringer Ingelheim Investigational Site | Bursa | Turkey | ||
| 667 | 205.389.3819 Boehringer Ingelheim Investigational Site | Erzurum | Turkey | ||
| 668 | 205.389.3812 Boehringer Ingelheim Investigational Site | Istanbul | Turkey | ||
| 669 | 205.389.3827 Boehringer Ingelheim Investigational Site | Izmir | Turkey | ||
| 670 | 205.389.3813 Boehringer Ingelheim Investigational Site | Izmit | Turkey | ||
| 671 | 205.389.3820 Boehringer Ingelheim Investigational Site | Kahramanmaras | Turkey | ||
| 672 | 205.389.3825 Boehringer Ingelheim Investigational Site | Malatya | Turkey | ||
| 673 | 205.389.3809 Boehringer Ingelheim Investigational Site | Sihhiye Ankara | Turkey | ||
| 674 | 205.389.3807 Boehringer Ingelheim Investigational Site | Yenisehir-IZMIR | Turkey | ||
| 675 | 205.389.3521 Boehringer Ingelheim Investigational Site | AR Crimea | Ukraine | ||
| 676 | 205.389.3516 Boehringer Ingelheim Investigational Site | Cherkassy | Ukraine | ||
| 677 | 205.389.3549 Boehringer Ingelheim Investigational Site | Chernivtsi | Ukraine | ||
| 678 | 205.389.3509 Boehringer Ingelheim Investigational Site | Dnipropetrovsk | Ukraine | ||
| 679 | 205.389.3510 Boehringer Ingelheim Investigational Site | Dnipropetrovsk | Ukraine | ||
| 680 | 205.389.3511 Boehringer Ingelheim Investigational Site | Dnipropetrovsk | Ukraine | ||
| 681 | 205.389.3523 Boehringer Ingelheim Investigational Site | Dnipropetrovsk | Ukraine | ||
| 682 | 205.389.3514 Boehringer Ingelheim Investigational Site | Donetsk | Ukraine | ||
| 683 | 205.389.3524 Boehringer Ingelheim Investigational Site | Donetsk | Ukraine | ||
| 684 | 205.389.3533 Boehringer Ingelheim Investigational Site | Ivano-Frankivsk | Ukraine | ||
| 685 | 205.389.3506 Boehringer Ingelheim Investigational Site | Kharkiv | Ukraine | ||
| 686 | 205.389.3507 Boehringer Ingelheim Investigational Site | Kharkiv | Ukraine | ||
| 687 | 205.389.3508 Boehringer Ingelheim Investigational Site | Kharkiv | Ukraine | ||
| 688 | 205.389.3520 Boehringer Ingelheim Investigational Site | Kharkiv | Ukraine | ||
| 689 | 205.389.3522 Boehringer Ingelheim Investigational Site | Kharkiv | Ukraine | ||
| 690 | 205.389.3532 Boehringer Ingelheim Investigational Site | Kharkiv | Ukraine | ||
| 691 | 205.389.3539 Boehringer Ingelheim Investigational Site | Kharkiv | Ukraine | ||
| 692 | 205.389.3541 Boehringer Ingelheim Investigational Site | Kharkiv | Ukraine | ||
| 693 | 205.389.3543 Boehringer Ingelheim Investigational Site | Kharkiv | Ukraine | ||
| 694 | 205.389.3555 Boehringer Ingelheim Investigational Site | Kharkiv | Ukraine | ||
| 695 | 205.389.3501 Boehringer Ingelheim Investigational Site | Kiev | Ukraine | ||
| 696 | 205.389.3502 Boehringer Ingelheim Investigational Site | Kiev | Ukraine | ||
| 697 | 205.389.3503 Boehringer Ingelheim Investigational Site | Kiev | Ukraine | ||
| 698 | 205.389.3550 Boehringer Ingelheim Investigational Site | Kiev | Ukraine | ||
| 699 | 205.389.3552 Boehringer Ingelheim Investigational Site | Kiev | Ukraine | ||
| 700 | 205.389.3553 Boehringer Ingelheim Investigational Site | Kiev | Ukraine | ||
| 701 | 205.389.3504 Boehringer Ingelheim Investigational Site | Kyiv | Ukraine | ||
| 702 | 205.389.3525 Boehringer Ingelheim Investigational Site | Kyiv | Ukraine | ||
| 703 | 205.389.3526 Boehringer Ingelheim Investigational Site | Kyiv | Ukraine | ||
| 704 | 205.389.3528 Boehringer Ingelheim Investigational Site | Kyiv | Ukraine | ||
| 705 | 205.389.3534 Boehringer Ingelheim Investigational Site | Kyiv | Ukraine | ||
| 706 | 205.389.3535 Boehringer Ingelheim Investigational Site | Kyiv | Ukraine | ||
| 707 | 205.389.3536 Boehringer Ingelheim Investigational Site | Kyiv | Ukraine | ||
| 708 | 205.389.3538 Boehringer Ingelheim Investigational Site | Kyiv | Ukraine | ||
| 709 | 205.389.3551 Boehringer Ingelheim Investigational Site | Kyiv | Ukraine | ||
| 710 | 205.389.3545 Boehringer Ingelheim Investigational Site | Lugansk | Ukraine | ||
| 711 | 205.389.3512 Boehringer Ingelheim Investigational Site | Lviv | Ukraine | ||
| 712 | 205.389.3530 Boehringer Ingelheim Investigational Site | Lviv | Ukraine | ||
| 713 | 205.389.3540 Boehringer Ingelheim Investigational Site | Lviv | Ukraine | ||
| 714 | 205.389.3554 Boehringer Ingelheim Investigational Site | Lviv | Ukraine | ||
| 715 | 205.389.3556 Boehringer Ingelheim Investigational Site | m.Donetsk | Ukraine | ||
| 716 | 205.389.3513 Boehringer Ingelheim Investigational Site | m.Odesa | Ukraine | ||
| 717 | 205.389.3519 Boehringer Ingelheim Investigational Site | Odesa | Ukraine | ||
| 718 | 205.389.3542 Boehringer Ingelheim Investigational Site | Odesa | Ukraine | ||
| 719 | 205.389.3527 Boehringer Ingelheim Investigational Site | Odessa | Ukraine | ||
| 720 | 205.389.3531 Boehringer Ingelheim Investigational Site | Poltava | Ukraine | ||
| 721 | 205.389.3517 Boehringer Ingelheim Investigational Site | Simferopil | Ukraine | ||
| 722 | 205.389.3518 Boehringer Ingelheim Investigational Site | Ternopil | Ukraine | ||
| 723 | 205.389.3529 Boehringer Ingelheim Investigational Site | Vinnitsa | Ukraine | ||
| 724 | 205.389.3515 Boehringer Ingelheim Investigational Site | Zaporizhzhya | Ukraine | ||
| 725 | 205.389.3547 Boehringer Ingelheim Investigational Site | Zaporizhzhya | Ukraine | ||
| 726 | 205.389.3548 Boehringer Ingelheim Investigational Site | Zaporizhzhya | Ukraine | ||
| 727 | 205.389.3601 Boehringer Ingelheim Investigational Site | Bath | United Kingdom | ||
| 728 | 205.389.3630 Boehringer Ingelheim Investigational Site | Bexhill on Sea | United Kingdom | ||
| 729 | 205.389.3636 Boehringer Ingelheim Investigational Site | Bexhill-on-Sea | United Kingdom | ||
| 730 | 205.389.3608 Boehringer Ingelheim Investigational Site | Birmingham | United Kingdom | ||
| 731 | 205.389.3605 Boehringer Ingelheim Investigational Site | Blackburn | United Kingdom | ||
| 732 | 205.389.3609 Boehringer Ingelheim Investigational Site | Bolton | United Kingdom | ||
| 733 | 205.389.3640 Boehringer Ingelheim Investigational Site | Burbage | United Kingdom | ||
| 734 | 205.389.3643 Boehringer Ingelheim Investigational Site | Chesterfield | United Kingdom | ||
| 735 | 205.389.3627 Boehringer Ingelheim Investigational Site | Corsham | United Kingdom | ||
| 736 | 205.389.3606 Boehringer Ingelheim Investigational Site | Coventry | United Kingdom | ||
| 737 | 205.389.3633 Boehringer Ingelheim Investigational Site | Coventry | United Kingdom | ||
| 738 | 205.389.3639 Boehringer Ingelheim Investigational Site | Frome | United Kingdom | ||
| 739 | 205.389.3602 Boehringer Ingelheim Investigational Site | Glasgow | United Kingdom | ||
| 740 | 205.389.3632 Boehringer Ingelheim Investigational Site | Irvine | United Kingdom | ||
| 741 | 205.389.3623 Boehringer Ingelheim Investigational Site | London | United Kingdom | ||
| 742 | 205.389.3638 Boehringer Ingelheim Investigational Site | Middlesex | United Kingdom | ||
| 743 | 205.389.3616 Boehringer Ingelheim Investigational Site | Newcastle upon Tyne | United Kingdom | ||
| 744 | 205.389.3618 Boehringer Ingelheim Investigational Site | Paisley | United Kingdom | ||
| 745 | 205.389.3622 Boehringer Ingelheim Investigational Site | Radstock | United Kingdom | ||
| 746 | 205.389.3626 Boehringer Ingelheim Investigational Site | Randalstown | United Kingdom | ||
| 747 | 205.389.3604 Boehringer Ingelheim Investigational Site | Soham | United Kingdom | ||
| 748 | 205.389.3613 Boehringer Ingelheim Investigational Site | St Just, Penzance | United Kingdom | ||
| 749 | 205.389.3624 Boehringer Ingelheim Investigational Site | Sunderland | United Kingdom | ||
| 750 | 205.389.3635 Boehringer Ingelheim Investigational Site | Wansford, Peterborough | United Kingdom | ||
| 751 | 205.389.3631 Boehringer Ingelheim Investigational Site | Windsor | United Kingdom | ||
| 752 | 205.389.3612 Boehringer Ingelheim Investigational Site | Wrexham | United Kingdom |
Sponsors and Collaborators
- Boehringer Ingelheim
- Pfizer
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00563381
Other Study ID Numbers:
- 205.389
- EUDRACT2007-001840-33
First Posted:
Nov 26, 2007
Last Update Posted:
Dec 24, 2013
Last Verified:
Jul 1, 2012
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | There were 8 patients (4:4 on Tiotropium and Salmeterol respectively) randomized but not treated |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Period Title: Overall Study | ||
| STARTED | 3707 | 3669 |
| COMPLETED | 3122 | 3021 |
| NOT COMPLETED | 585 | 648 |
Baseline Characteristics
| Arm/Group Title | Tiotropium | Salmeterol | Total |
|---|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily | Total of all reporting groups |
| Overall Participants | 3707 | 3669 | 7376 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
62.9
(9.0)
|
62.8
(9.0)
|
62.9
(9.0)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
948
25.6%
|
922
25.1%
|
1870
25.4%
|
| Male |
2759
74.4%
|
2747
74.9%
|
5506
74.6%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| Asian |
5
0.1%
|
3
0.1%
|
8
0.1%
|
| Black |
9
0.2%
|
9
0.2%
|
18
0.2%
|
| White |
3693
99.6%
|
3657
99.7%
|
7350
99.6%
|
Outcome Measures
| Title | First Occurrence of (Moderate or Severe) COPD Exacerbation |
|---|---|
| Description | First occurrence analysed by Cox regression as time to first exacerbation and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Number [number of first occurrences] |
1277
|
1414
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Treatment effect adjusted for pooled centre | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.83 | |
| Confidence Interval |
() 95% 0.77 to 0.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | COPD Exacerbations Per Patient-year Leading to Hospitalisation |
|---|---|
| Description | An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Mean (95% Confidence Interval) [Hospitalizations per patient-year] |
0.09
|
0.13
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium vs. Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Poisson regression | |
| Comments | Poisson regression correcting for overdisperion and adjusted for treatment exposure | |
| Method of Estimation | Estimation Parameter | Rate ratio (ratio of incidence rates) |
| Estimated Value | 0.73 | |
| Confidence Interval |
() 95% 0.66 to 0.82 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.04 |
|
| Estimation Comments | ||
| Title | Number of Participants With at Least One COPD Exacerbation |
|---|---|
| Description | An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Participants with (at least one) event |
1277
34.4%
|
1414
38.5%
|
| Participants with no event |
2430
65.6%
|
2255
61.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.90 | |
| Confidence Interval |
() 95% 0.85 to 0.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | COPD Exacerbations Per Patient-year |
|---|---|
| Description | |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Mean (95% Confidence Interval) [exacerbations per patient-year] |
0.64
|
0.72
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0017 |
| Comments | ||
| Method | Poisson regression | |
| Comments | Poisson regression correcting for overdisperion and adjusted for treatment exposure | |
| Method of Estimation | Estimation Parameter | Rate ratio (ratio of incidence rates) |
| Estimated Value | 0.89 | |
| Confidence Interval |
() 95% 0.83 to 0.96 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.03 |
|
| Estimation Comments | ||
| Title | First Occurrence of COPD Exacerbation Leading to Hospitalization |
|---|---|
| Description | First occurrence analysed by Cox regression as time to first exacerbation leading to hospitalisation and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Number [number of first occurrences] |
262
|
336
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Treatment effect adjusted for pooled centre | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.72 | |
| Confidence Interval |
() 95% 0.61 to 0.85 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With at Least One COPD Exacerbation Leading to Hospitalisation |
|---|---|
| Description | An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Participants with (at least one) event |
262
7.1%
|
336
9.2%
|
| Participants with no event |
3445
92.9%
|
3333
90.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.77 | |
| Confidence Interval |
() 95% 0.66 to 0.89 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Occurrence of Premature Discontinuation of Trial Medication |
|---|---|
| Description | Occurrence analysed by Cox regression as time to premature discontinuation of trial medication and reported as hazard ratio |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Number [number of first occurrences] |
585
|
648
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0242 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Treatment effect adjusted for pooled centre | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.88 | |
| Confidence Interval |
() 95% 0.78 to 0.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Premature Discontinuation of Trial Medication |
|---|---|
| Description | |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Participants with (at least one) event |
585
15.8%
|
648
17.7%
|
| Participants with no event |
3122
84.2%
|
3021
82.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0406 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.90 | |
| Confidence Interval |
() 95% 0.82 to 1.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | First Occurrence of COPD Exacerbation or Discontinuation of Trial Medication Because of Worsening of Underlying Disease, Whichever Comes First |
|---|---|
| Description | First occurrence analysed by Cox regression as time to first exacerbation or discontinuation of trial medication because of worsening of underlying disease, whichever comes first and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Number [number of first occurrences] |
1316
|
1448
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Treatment effect adjusted for pooled centre | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.84 | |
| Confidence Interval |
() 95% 0.78 to 0.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | First Occurrence of COPD Exacerbations Treated With Systemic Steroids |
|---|---|
| Description | First occurrence analysed by Cox regression as time to first exacerbation treated with systemic steroids and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Number [number of first occurrences] |
715
|
852
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Treatment effect adjusted for pooled centre | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.77 | |
| Confidence Interval |
() 95% 0.69 to 0.85 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | First Occurrence of COPD Exacerbations Treated With Antibiotics |
|---|---|
| Description | First occurrence analysed by Cox regression as time to first exacerbation treated with antibiotics and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Number [number of first occurrences] |
1154
|
1259
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Treatment effect adjusted for pooled centre | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.85 | |
| Confidence Interval |
() 95% 0.78 to 0.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | First Occurrence of COPD Exacerbations Treated With Systemic Steroids and Antibiotics |
|---|---|
| Description | First occurrence analysed by Cox regression as time to first exacerbation treated with systemic steroids and antibiotics and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Number [number of first occurrences] |
562
|
671
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Treatment effect adjusted for pooled centre | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.76 | |
| Confidence Interval |
() 95% 0.68 to 0.86 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | COPD Exacerbations Treated With Systemic Steroids Per Patient-year |
|---|---|
| Description | An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Mean (95% Confidence Interval) [exacerbations per patient-year] |
0.33
|
0.41
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Poisson regression | |
| Comments | Poisson regression correcting for overdispersion and adjusted for treatment exposure | |
| Method of Estimation | Estimation Parameter | Rate ratio (ratio of incidence rates) |
| Estimated Value | 0.82 | |
| Confidence Interval |
() 95% 0.76 to 0.90 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.04 |
|
| Estimation Comments | ||
| Title | COPD Exacerbations Treated With Antibiotics Per Patient-year |
|---|---|
| Description | An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Mean (95% Confidence Interval) [exacerbations per patient-year] |
0.53
|
0.59
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0036 |
| Comments | ||
| Method | Poisson regression | |
| Comments | Poisson regression correcting for overdisperion and adjusted for treatment exposure | |
| Method of Estimation | Estimation Parameter | Rate ratio (ratio of incidence rates) |
| Estimated Value | 0.90 | |
| Confidence Interval |
() 95% 0.84 to 0.97 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.03 |
|
| Estimation Comments | ||
| Title | COPD Exacerbations Treated With Systemic Steroids and Antibiotics Per Patient-year |
|---|---|
| Description | An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Time Frame | 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 3707 | 3669 |
| Mean (95% Confidence Interval) [exacerbations per patient-year] |
0.23
|
0.28
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Poisson regression | |
| Comments | Poisson regression correcting for overdisperion and adjusted for treatment exposure | |
| Method of Estimation | Estimation Parameter | Rate ratio (ratio of incidence rates) |
| Estimated Value | 0.80 | |
| Confidence Interval |
() 95% 0.73 to 0.88 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.04 |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 1 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2446 | 2434 |
| Mean (Standard Error) [liter per minute (L/min)] |
222.85
(0.81)
|
224.45
(0.81)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1035 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | Mixed effects repeated measures model (MMRM) (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -1.60 | |
| Confidence Interval |
() 95% -3.53 to 0.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 2 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2413 | 2377 |
| Mean (Standard Error) [liter per minute (L/min)] |
225.15
(0.81)
|
227.21
(0.81)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0369 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | Mixed effects repeated measures model (MRMM)(fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week). | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -2.06 | |
| Confidence Interval |
() 95% -3.99 to -0.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 3 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2394 | 2357 |
| Mean (Standard Error) [liter per minute (L/min)] |
226.31
(0.81)
|
228.38
(0.81)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0362 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -2.07 | |
| Confidence Interval |
() 95% -4.00 to -0.13 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 4 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2380 | 2349 |
| Mean (Standard Error) [liter per minute (L/min)] |
227.37
(0.81)
|
229.25
(0.81)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0573 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -1.88 | |
| Confidence Interval |
() 95% -3.82 to 0.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 5 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2360 | 2335 |
| Mean (Standard Error) [liter per minute (L/min)] |
228.27
(0.81)
|
229.37
(0.81)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2641 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -1.10 | |
| Confidence Interval |
() 95% -3.04 to 0.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 6 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2351 | 2319 |
| Mean (Standard Error) [liter per minute (L/min)] |
228.80
(0.82)
|
229.81
(0.81)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3068 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -1.01 | |
| Confidence Interval |
() 95% -2.95 to 0.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 7 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2339 | 2306 |
| Mean (Standard Error) [liter per minute (L/min)] |
229.35
(0.82)
|
230.13
(0.82)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4299 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -0.78 | |
| Confidence Interval |
() 95% -2.72 to 1.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 8 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2319 | 2278 |
| Mean (Standard Error) [liter per minute (L/min)] |
229.95
(0.82)
|
230.43
(0.82)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6277 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -0.48 | |
| Confidence Interval |
() 95% -2.42 to 1.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 9 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2279 | 2234 |
| Mean (Standard Error) [liter per minute (L/min)] |
229.72
(0.82)
|
230.57
(0.82)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3931 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -0.85 | |
| Confidence Interval |
() 95% -2.80 to 1.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 10 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2285 | 2235 |
| Mean (Standard Error) [liter per minute (L/min)] |
230.30
(0.82)
|
231.27
(0.82)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3297 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -0.97 | |
| Confidence Interval |
() 95% -2.92 to 0.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 11 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2289 | 2228 |
| Mean (Standard Error) [liter per minute (L/min)] |
230.61
(0.82)
|
231.91
(0.82)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1904 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -1.30 | |
| Confidence Interval |
() 95% -3.25 to 0.65 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 12 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2286 | 2214 |
| Mean (Standard Error) [liter per minute (L/min)] |
231.04
(0.82)
|
232.04
(0.82)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3172 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -0.99 | |
| Confidence Interval |
() 95% -2.94 to 0.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 13 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2278 | 2212 |
| Mean (Standard Error) [liter per minute (L/min)] |
231.23
(0.82)
|
231.89
(0.82)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5017 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -0.67 | |
| Confidence Interval |
() 95% -2.62 to 1.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 14 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2264 | 2211 |
| Mean (Standard Error) [liter per minute (L/min)] |
231.19
(0.82)
|
232.42
(0.82)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2174 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -1.23 | |
| Confidence Interval |
() 95% -3.18 to 0.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 15 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2256 | 2193 |
| Mean (Standard Error) [liter per minute (L/min)] |
231.64
(0.82)
|
232.75
(0.82)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2682 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -1.10 | |
| Confidence Interval |
() 95% -3.05 to 0.85 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 16 |
|---|---|
| Description | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples |
| Arm/Group Title | Tiotropium | Salmeterol |
|---|---|---|
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily |
| Measure Participants | 2240 | 2174 |
| Mean (Standard Error) [liter per minute (L/min)] |
232.06
(0.82)
|
232.65
(0.82)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium, Salmeterol |
|---|---|---|
| Comments | Tiotropium versus Salmeterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5520 |
| Comments | ||
| Method | Mixed Effects Repeated Measures Model | |
| Comments | MMRM (fixed terms: treatment, centre, week, treatment*week; covariates: baseline PEFR, baseline PEFR*week) | |
| Method of Estimation | Estimation Parameter | difference in peak expiratory flow rates |
| Estimated Value | -0.59 | |
| Confidence Interval |
() 95% -2.55 to 1.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | 52 weeks (while on treatment with study drugs + 30 days) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The term "Chronic obstructive pulmonary disease" under "Other Adverse Events" contains number of patients with exacerbations which the investigator entered via AE reporting. They were consolidated with the exacerbation events used for efficacy analysis which were collected via separate designated case report form pages. | |||
| Arm/Group Title | Tiotropium | Salmeterol | ||
| Arm/Group Description | Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily | ||
All Cause Mortality |
||||
| Tiotropium | Salmeterol | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Tiotropium | Salmeterol | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 545/3707 (14.7%) | 606/3669 (16.5%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/3707 (0%) | 3/3669 (0.1%) | ||
| Haemorrhagic anaemia | 1/3707 (0%) | 0/3669 (0%) | ||
| Iron deficiency anaemia | 1/3707 (0%) | 0/3669 (0%) | ||
| Lymphadenopathy | 0/3707 (0%) | 1/3669 (0%) | ||
| Splenitis | 1/3707 (0%) | 0/3669 (0%) | ||
| Cardiac disorders | ||||
| Acute coronary syndrome | 2/3707 (0.1%) | 2/3669 (0.1%) | ||
| Acute myocardial infarction | 3/3707 (0.1%) | 1/3669 (0%) | ||
| Angina pectoris | 9/3707 (0.2%) | 5/3669 (0.1%) | ||
| Angina unstable | 2/3707 (0.1%) | 2/3669 (0.1%) | ||
| Arrhythmia | 1/3707 (0%) | 1/3669 (0%) | ||
| Arrhythmia supraventricular | 1/3707 (0%) | 0/3669 (0%) | ||
| Arteriosclerosis coronary artery | 1/3707 (0%) | 1/3669 (0%) | ||
| Atrial fibrillation | 12/3707 (0.3%) | 14/3669 (0.4%) | ||
| Atrial flutter | 1/3707 (0%) | 1/3669 (0%) | ||
| Atrioventricular block | 0/3707 (0%) | 1/3669 (0%) | ||
| Atrioventricular block second degree | 0/3707 (0%) | 1/3669 (0%) | ||
| Bradycardia | 0/3707 (0%) | 1/3669 (0%) | ||
| Cardiac arrest | 2/3707 (0.1%) | 2/3669 (0.1%) | ||
| Cardiac failure | 17/3707 (0.5%) | 21/3669 (0.6%) | ||
| Cardiac failure acute | 2/3707 (0.1%) | 1/3669 (0%) | ||
| Cardiac failure chronic | 0/3707 (0%) | 1/3669 (0%) | ||
| Cardiac failure congestive | 1/3707 (0%) | 0/3669 (0%) | ||
| Cardiac fibrillation | 1/3707 (0%) | 0/3669 (0%) | ||
| Cardiogenic shock | 1/3707 (0%) | 0/3669 (0%) | ||
| Cardiomyopathy | 3/3707 (0.1%) | 0/3669 (0%) | ||
| Cardiopulmonary failure | 4/3707 (0.1%) | 3/3669 (0.1%) | ||
| Cardiovascular disorder | 0/3707 (0%) | 1/3669 (0%) | ||
| Cardiovascular insufficiency | 4/3707 (0.1%) | 0/3669 (0%) | ||
| Congestive cardiomyopathy | 0/3707 (0%) | 1/3669 (0%) | ||
| Cor pulmonale | 4/3707 (0.1%) | 5/3669 (0.1%) | ||
| Cor pulmonale chronic | 1/3707 (0%) | 2/3669 (0.1%) | ||
| Coronary artery disease | 4/3707 (0.1%) | 5/3669 (0.1%) | ||
| Coronary artery insufficiency | 1/3707 (0%) | 2/3669 (0.1%) | ||
| Coronary artery stenosis | 2/3707 (0.1%) | 1/3669 (0%) | ||
| Dressler's syndrome | 1/3707 (0%) | 0/3669 (0%) | ||
| Extrasystoles | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Ischaemic cardiomyopathy | 1/3707 (0%) | 1/3669 (0%) | ||
| Left ventricular failure | 2/3707 (0.1%) | 0/3669 (0%) | ||
| Mitral valve stenosis | 1/3707 (0%) | 0/3669 (0%) | ||
| Myocardial infarction | 20/3707 (0.5%) | 13/3669 (0.4%) | ||
| Myocardial ischaemia | 11/3707 (0.3%) | 6/3669 (0.2%) | ||
| Nodal rhythm | 1/3707 (0%) | 0/3669 (0%) | ||
| Pericarditis | 0/3707 (0%) | 1/3669 (0%) | ||
| Postinfarction angina | 1/3707 (0%) | 0/3669 (0%) | ||
| Right ventricular failure | 1/3707 (0%) | 4/3669 (0.1%) | ||
| Sinoatrial block | 0/3707 (0%) | 1/3669 (0%) | ||
| Sinus bradycardia | 1/3707 (0%) | 0/3669 (0%) | ||
| Supraventricular tachycardia | 1/3707 (0%) | 0/3669 (0%) | ||
| Tachyarrhythmia | 1/3707 (0%) | 0/3669 (0%) | ||
| Tachycardia | 1/3707 (0%) | 1/3669 (0%) | ||
| Ventricular fibrillation | 0/3707 (0%) | 1/3669 (0%) | ||
| Ear and labyrinth disorders | ||||
| Tinnitus | 0/3707 (0%) | 1/3669 (0%) | ||
| Tympanosclerosis | 0/3707 (0%) | 1/3669 (0%) | ||
| Vertigo | 0/3707 (0%) | 1/3669 (0%) | ||
| Vestibular ataxia | 1/3707 (0%) | 0/3669 (0%) | ||
| Vestibular disorder | 1/3707 (0%) | 0/3669 (0%) | ||
| Endocrine disorders | ||||
| Hypercalcaemia of malignancy | 0/3707 (0%) | 1/3669 (0%) | ||
| Hyperthyroidism | 0/3707 (0%) | 1/3669 (0%) | ||
| Hypoparathyroidism | 1/3707 (0%) | 0/3669 (0%) | ||
| Hypothyroidism | 1/3707 (0%) | 0/3669 (0%) | ||
| Eye disorders | ||||
| Cataract | 6/3707 (0.2%) | 3/3669 (0.1%) | ||
| Eye disorder | 1/3707 (0%) | 0/3669 (0%) | ||
| Eyelid ptosis | 1/3707 (0%) | 0/3669 (0%) | ||
| Glaucoma | 0/3707 (0%) | 1/3669 (0%) | ||
| Iridocyclitis | 0/3707 (0%) | 1/3669 (0%) | ||
| Retinal detachment | 0/3707 (0%) | 1/3669 (0%) | ||
| Scleritis | 1/3707 (0%) | 0/3669 (0%) | ||
| Visual impairment | 1/3707 (0%) | 0/3669 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 2/3707 (0.1%) | 4/3669 (0.1%) | ||
| Abdominal pain upper | 3/3707 (0.1%) | 0/3669 (0%) | ||
| Anal polyp | 0/3707 (0%) | 1/3669 (0%) | ||
| Colitis | 0/3707 (0%) | 1/3669 (0%) | ||
| Colonic polyp | 1/3707 (0%) | 0/3669 (0%) | ||
| Diarrhoea | 2/3707 (0.1%) | 2/3669 (0.1%) | ||
| Diverticulitis oesophageal | 0/3707 (0%) | 1/3669 (0%) | ||
| Diverticulum | 0/3707 (0%) | 1/3669 (0%) | ||
| Duodenal perforation | 0/3707 (0%) | 1/3669 (0%) | ||
| Duodenal ulcer | 3/3707 (0.1%) | 2/3669 (0.1%) | ||
| Duodenal ulcer haemorrhage | 1/3707 (0%) | 1/3669 (0%) | ||
| Dyspepsia | 0/3707 (0%) | 1/3669 (0%) | ||
| Enamel anomaly | 0/3707 (0%) | 1/3669 (0%) | ||
| Enteritis | 1/3707 (0%) | 0/3669 (0%) | ||
| Epiploic appendagitis | 1/3707 (0%) | 0/3669 (0%) | ||
| Gastric ulcer | 1/3707 (0%) | 1/3669 (0%) | ||
| Gastric ulcer haemorrhage | 2/3707 (0.1%) | 1/3669 (0%) | ||
| Gastric ulcer perforation | 1/3707 (0%) | 0/3669 (0%) | ||
| Gastritis | 3/3707 (0.1%) | 2/3669 (0.1%) | ||
| Gastritis erosive | 1/3707 (0%) | 0/3669 (0%) | ||
| Gastroduodenitis | 0/3707 (0%) | 1/3669 (0%) | ||
| Gastrointestinal haemorrhage | 0/3707 (0%) | 1/3669 (0%) | ||
| Haemorrhoidal haemorrhage | 0/3707 (0%) | 1/3669 (0%) | ||
| Haemorrhoids | 2/3707 (0.1%) | 1/3669 (0%) | ||
| Ileus | 1/3707 (0%) | 0/3669 (0%) | ||
| Inflammatory bowel disease | 0/3707 (0%) | 1/3669 (0%) | ||
| Inguinal hernia | 2/3707 (0.1%) | 1/3669 (0%) | ||
| Intestinal infarction | 0/3707 (0%) | 1/3669 (0%) | ||
| Intestinal ischaemia | 1/3707 (0%) | 0/3669 (0%) | ||
| Intestinal obstruction | 1/3707 (0%) | 0/3669 (0%) | ||
| Mesenteric artery thrombosis | 1/3707 (0%) | 0/3669 (0%) | ||
| Pancreatic necrosis | 1/3707 (0%) | 0/3669 (0%) | ||
| Pancreatitis acute | 2/3707 (0.1%) | 2/3669 (0.1%) | ||
| Pancreatitis haemorrhagic | 1/3707 (0%) | 0/3669 (0%) | ||
| Pancreatitis relapsing | 0/3707 (0%) | 1/3669 (0%) | ||
| Parotid gland enlargement | 0/3707 (0%) | 1/3669 (0%) | ||
| Peptic ulcer | 0/3707 (0%) | 1/3669 (0%) | ||
| Peptic ulcer perforation | 1/3707 (0%) | 0/3669 (0%) | ||
| Peritonitis | 1/3707 (0%) | 1/3669 (0%) | ||
| Rectal polyp | 1/3707 (0%) | 0/3669 (0%) | ||
| Subileus | 0/3707 (0%) | 1/3669 (0%) | ||
| Varices oesophageal | 0/3707 (0%) | 1/3669 (0%) | ||
| General disorders | ||||
| Chest pain | 4/3707 (0.1%) | 6/3669 (0.2%) | ||
| Chills | 0/3707 (0%) | 1/3669 (0%) | ||
| Death | 3/3707 (0.1%) | 7/3669 (0.2%) | ||
| Device dislocation | 1/3707 (0%) | 1/3669 (0%) | ||
| Drowning | 2/3707 (0.1%) | 0/3669 (0%) | ||
| Drug intolerance | 0/3707 (0%) | 1/3669 (0%) | ||
| Gait disturbance | 0/3707 (0%) | 1/3669 (0%) | ||
| General physical health deterioration | 0/3707 (0%) | 1/3669 (0%) | ||
| Hernia | 0/3707 (0%) | 1/3669 (0%) | ||
| Hypothermia | 0/3707 (0%) | 1/3669 (0%) | ||
| Inflammation | 0/3707 (0%) | 1/3669 (0%) | ||
| Malaise | 0/3707 (0%) | 1/3669 (0%) | ||
| Multi-organ failure | 5/3707 (0.1%) | 0/3669 (0%) | ||
| Oedema peripheral | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Pyrexia | 1/3707 (0%) | 1/3669 (0%) | ||
| Sudden cardiac death | 0/3707 (0%) | 1/3669 (0%) | ||
| Sudden death | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Hepatobiliary disorders | ||||
| Bile duct obstruction | 1/3707 (0%) | 0/3669 (0%) | ||
| Cholangitis | 0/3707 (0%) | 1/3669 (0%) | ||
| Cholecystitis | 2/3707 (0.1%) | 3/3669 (0.1%) | ||
| Cholecystitis acute | 3/3707 (0.1%) | 0/3669 (0%) | ||
| Cholecystitis chronic | 1/3707 (0%) | 0/3669 (0%) | ||
| Cholelithiasis | 3/3707 (0.1%) | 0/3669 (0%) | ||
| Gallbladder polyp | 0/3707 (0%) | 1/3669 (0%) | ||
| Jaundice | 0/3707 (0%) | 1/3669 (0%) | ||
| Liver disorder | 2/3707 (0.1%) | 1/3669 (0%) | ||
| Immune system disorders | ||||
| Anaphylactic reaction | 0/3707 (0%) | 1/3669 (0%) | ||
| Infections and infestations | ||||
| Actinomycosis | 0/3707 (0%) | 1/3669 (0%) | ||
| Appendicitis | 2/3707 (0.1%) | 1/3669 (0%) | ||
| Borrelia infection | 0/3707 (0%) | 1/3669 (0%) | ||
| Bronchiectasis | 1/3707 (0%) | 0/3669 (0%) | ||
| Bronchitis | 3/3707 (0.1%) | 1/3669 (0%) | ||
| Bronchitis bacterial | 1/3707 (0%) | 1/3669 (0%) | ||
| Bronchopneumonia | 4/3707 (0.1%) | 3/3669 (0.1%) | ||
| Candidiasis | 1/3707 (0%) | 0/3669 (0%) | ||
| Cellulitis | 0/3707 (0%) | 3/3669 (0.1%) | ||
| Cholangitis suppurative | 1/3707 (0%) | 0/3669 (0%) | ||
| Clostridium difficile colitis | 0/3707 (0%) | 1/3669 (0%) | ||
| Dermatitis infected | 1/3707 (0%) | 0/3669 (0%) | ||
| Diabetic gangrene | 0/3707 (0%) | 1/3669 (0%) | ||
| Diverticulitis | 0/3707 (0%) | 1/3669 (0%) | ||
| Empyema | 1/3707 (0%) | 0/3669 (0%) | ||
| Erysipelas | 0/3707 (0%) | 1/3669 (0%) | ||
| Gangrene | 0/3707 (0%) | 1/3669 (0%) | ||
| Gastroenteritis | 3/3707 (0.1%) | 0/3669 (0%) | ||
| Groin abscess | 0/3707 (0%) | 1/3669 (0%) | ||
| H1N1 influenza | 1/3707 (0%) | 0/3669 (0%) | ||
| Hepatitis B | 0/3707 (0%) | 1/3669 (0%) | ||
| Hepatitis C | 1/3707 (0%) | 0/3669 (0%) | ||
| Herpes zoster | 1/3707 (0%) | 0/3669 (0%) | ||
| Infection | 0/3707 (0%) | 1/3669 (0%) | ||
| Infective exacerbation of chronic obstructive airways disease | 2/3707 (0.1%) | 4/3669 (0.1%) | ||
| Influenza | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Kidney infection | 1/3707 (0%) | 0/3669 (0%) | ||
| Laryngitis | 1/3707 (0%) | 0/3669 (0%) | ||
| Lobar pneumonia | 3/3707 (0.1%) | 1/3669 (0%) | ||
| Lower respiratory tract infection | 3/3707 (0.1%) | 1/3669 (0%) | ||
| Lung abscess | 1/3707 (0%) | 2/3669 (0.1%) | ||
| Lyme disease | 1/3707 (0%) | 0/3669 (0%) | ||
| Nosocomial infection | 0/3707 (0%) | 1/3669 (0%) | ||
| Oesophageal candidiasis | 0/3707 (0%) | 1/3669 (0%) | ||
| Oral candidiasis | 1/3707 (0%) | 0/3669 (0%) | ||
| Orchitis | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Otitis media chronic | 0/3707 (0%) | 1/3669 (0%) | ||
| Peritonsillar abscess | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Pilonidal cyst | 0/3707 (0%) | 1/3669 (0%) | ||
| Pneumonia | 54/3707 (1.5%) | 64/3669 (1.7%) | ||
| Pneumonia necrotising | 0/3707 (0%) | 1/3669 (0%) | ||
| Pneumonia staphylococcal | 1/3707 (0%) | 0/3669 (0%) | ||
| Pneumonia streptococcal | 1/3707 (0%) | 0/3669 (0%) | ||
| Pneumonia viral | 0/3707 (0%) | 1/3669 (0%) | ||
| Post procedural infection | 0/3707 (0%) | 1/3669 (0%) | ||
| Pseudomembranous colitis | 0/3707 (0%) | 1/3669 (0%) | ||
| Pulmonary tuberculosis | 1/3707 (0%) | 1/3669 (0%) | ||
| Pyelonephritis | 2/3707 (0.1%) | 1/3669 (0%) | ||
| Pyothorax | 0/3707 (0%) | 1/3669 (0%) | ||
| Respiratory tract infection | 1/3707 (0%) | 4/3669 (0.1%) | ||
| Rickettsiosis | 1/3707 (0%) | 0/3669 (0%) | ||
| Sepsis | 3/3707 (0.1%) | 2/3669 (0.1%) | ||
| Septic shock | 2/3707 (0.1%) | 2/3669 (0.1%) | ||
| Sinusitis | 0/3707 (0%) | 1/3669 (0%) | ||
| Staphylococcal infection | 0/3707 (0%) | 1/3669 (0%) | ||
| Staphylococcal sepsis | 2/3707 (0.1%) | 0/3669 (0%) | ||
| Subcutaneous abscess | 1/3707 (0%) | 0/3669 (0%) | ||
| Superinfection bacterial | 1/3707 (0%) | 0/3669 (0%) | ||
| Tracheobronchitis | 1/3707 (0%) | 0/3669 (0%) | ||
| Tuberculosis | 1/3707 (0%) | 2/3669 (0.1%) | ||
| Upper respiratory tract infection | 0/3707 (0%) | 4/3669 (0.1%) | ||
| Urinary tract infection | 5/3707 (0.1%) | 1/3669 (0%) | ||
| Wound sepsis | 1/3707 (0%) | 0/3669 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Accident at work | 0/3707 (0%) | 1/3669 (0%) | ||
| Alcohol poisoning | 0/3707 (0%) | 1/3669 (0%) | ||
| Arthropod sting | 0/3707 (0%) | 1/3669 (0%) | ||
| Cerebral haemorrhage traumatic | 0/3707 (0%) | 1/3669 (0%) | ||
| Chest injury | 1/3707 (0%) | 1/3669 (0%) | ||
| Concussion | 1/3707 (0%) | 0/3669 (0%) | ||
| Contusion | 2/3707 (0.1%) | 2/3669 (0.1%) | ||
| Fall | 9/3707 (0.2%) | 7/3669 (0.2%) | ||
| Femoral neck fracture | 1/3707 (0%) | 1/3669 (0%) | ||
| Femur fracture | 2/3707 (0.1%) | 1/3669 (0%) | ||
| Fibula fracture | 1/3707 (0%) | 0/3669 (0%) | ||
| Foot fracture | 0/3707 (0%) | 1/3669 (0%) | ||
| Frostbite | 0/3707 (0%) | 1/3669 (0%) | ||
| Hand fracture | 1/3707 (0%) | 0/3669 (0%) | ||
| Head injury | 3/3707 (0.1%) | 1/3669 (0%) | ||
| Humerus fracture | 1/3707 (0%) | 2/3669 (0.1%) | ||
| Joint injury | 1/3707 (0%) | 0/3669 (0%) | ||
| Ligament rupture | 1/3707 (0%) | 0/3669 (0%) | ||
| Lumbar vertebral fracture | 0/3707 (0%) | 1/3669 (0%) | ||
| Multiple drug overdose | 0/3707 (0%) | 1/3669 (0%) | ||
| Multiple injuries | 0/3707 (0%) | 1/3669 (0%) | ||
| Muscle rupture | 1/3707 (0%) | 0/3669 (0%) | ||
| Postoperative wound complication | 1/3707 (0%) | 0/3669 (0%) | ||
| Radius fracture | 0/3707 (0%) | 1/3669 (0%) | ||
| Rib fracture | 4/3707 (0.1%) | 0/3669 (0%) | ||
| Road traffic accident | 4/3707 (0.1%) | 1/3669 (0%) | ||
| Spinal column injury | 1/3707 (0%) | 0/3669 (0%) | ||
| Spinal compression fracture | 0/3707 (0%) | 1/3669 (0%) | ||
| Spinal fracture | 0/3707 (0%) | 1/3669 (0%) | ||
| Subdural haematoma | 3/3707 (0.1%) | 0/3669 (0%) | ||
| Tendon rupture | 2/3707 (0.1%) | 0/3669 (0%) | ||
| Thermal burn | 0/3707 (0%) | 1/3669 (0%) | ||
| Thoracic vertebral fracture | 0/3707 (0%) | 1/3669 (0%) | ||
| Tibia fracture | 1/3707 (0%) | 0/3669 (0%) | ||
| Wound | 1/3707 (0%) | 0/3669 (0%) | ||
| Investigations | ||||
| Arteriogram coronary | 1/3707 (0%) | 0/3669 (0%) | ||
| Investigation | 0/3707 (0%) | 1/3669 (0%) | ||
| Weight decreased | 2/3707 (0.1%) | 1/3669 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Cachexia | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Diabetes mellitus | 1/3707 (0%) | 4/3669 (0.1%) | ||
| Diabetes mellitus inadequate control | 0/3707 (0%) | 1/3669 (0%) | ||
| Hyperglycaemia | 1/3707 (0%) | 0/3669 (0%) | ||
| Hyperkalaemia | 1/3707 (0%) | 0/3669 (0%) | ||
| Hypertriglyceridaemia | 1/3707 (0%) | 0/3669 (0%) | ||
| Hypokalaemia | 1/3707 (0%) | 1/3669 (0%) | ||
| Hypomagnesaemia | 1/3707 (0%) | 0/3669 (0%) | ||
| Hyponatraemia | 0/3707 (0%) | 1/3669 (0%) | ||
| Tetany | 1/3707 (0%) | 0/3669 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthritis | 0/3707 (0%) | 1/3669 (0%) | ||
| Arthropathy | 1/3707 (0%) | 0/3669 (0%) | ||
| Back pain | 2/3707 (0.1%) | 4/3669 (0.1%) | ||
| Bone pain | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Bursitis | 1/3707 (0%) | 0/3669 (0%) | ||
| Dental alveolar anomaly | 0/3707 (0%) | 1/3669 (0%) | ||
| Dupuytren's contracture | 1/3707 (0%) | 0/3669 (0%) | ||
| Intervertebral disc protrusion | 1/3707 (0%) | 1/3669 (0%) | ||
| Lumbar spinal stenosis | 0/3707 (0%) | 1/3669 (0%) | ||
| Muscle atrophy | 0/3707 (0%) | 1/3669 (0%) | ||
| Musculoskeletal chest pain | 0/3707 (0%) | 1/3669 (0%) | ||
| Neck pain | 0/3707 (0%) | 1/3669 (0%) | ||
| Osteoarthritis | 1/3707 (0%) | 5/3669 (0.1%) | ||
| Osteochondrosis | 1/3707 (0%) | 1/3669 (0%) | ||
| Osteoporosis | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Pain in extremity | 0/3707 (0%) | 1/3669 (0%) | ||
| Polymyalgia rheumatica | 0/3707 (0%) | 1/3669 (0%) | ||
| Rotator cuff syndrome | 1/3707 (0%) | 0/3669 (0%) | ||
| Soft tissue necrosis | 0/3707 (0%) | 1/3669 (0%) | ||
| Spinal disorder | 1/3707 (0%) | 0/3669 (0%) | ||
| Spinal osteoarthritis | 1/3707 (0%) | 0/3669 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal cell carcinoma | 3/3707 (0.1%) | 1/3669 (0%) | ||
| Benign breast neoplasm | 1/3707 (0%) | 0/3669 (0%) | ||
| Bladder cancer | 4/3707 (0.1%) | 1/3669 (0%) | ||
| Bladder neoplasm | 1/3707 (0%) | 0/3669 (0%) | ||
| Bladder papilloma | 1/3707 (0%) | 0/3669 (0%) | ||
| Bladder transitional cell carcinoma | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Breast cancer | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Bronchial carcinoma | 4/3707 (0.1%) | 2/3669 (0.1%) | ||
| Carcinoid tumour pulmonary | 0/3707 (0%) | 1/3669 (0%) | ||
| Cholesteatoma | 0/3707 (0%) | 1/3669 (0%) | ||
| Chronic lymphocytic leukaemia | 1/3707 (0%) | 0/3669 (0%) | ||
| Colon cancer | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Gallbladder cancer | 0/3707 (0%) | 1/3669 (0%) | ||
| Gastric cancer | 1/3707 (0%) | 0/3669 (0%) | ||
| Haemangioma of liver | 1/3707 (0%) | 0/3669 (0%) | ||
| Hepatic neoplasm | 1/3707 (0%) | 0/3669 (0%) | ||
| Hepatic neoplasm malignant | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Histiocytosis | 1/3707 (0%) | 0/3669 (0%) | ||
| Hypopharyngeal cancer | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Lip neoplasm malignant stage unspecified | 1/3707 (0%) | 0/3669 (0%) | ||
| Lipoma | 1/3707 (0%) | 0/3669 (0%) | ||
| Lung adenocarcinoma | 0/3707 (0%) | 1/3669 (0%) | ||
| Lung carcinoma cell type unspecified stage III | 1/3707 (0%) | 0/3669 (0%) | ||
| Lung neoplasm | 1/3707 (0%) | 1/3669 (0%) | ||
| Lung neoplasm malignant | 9/3707 (0.2%) | 7/3669 (0.2%) | ||
| Lung squamous cell carcinoma stage unspecified | 1/3707 (0%) | 2/3669 (0.1%) | ||
| Lymphocytic leukaemia | 0/3707 (0%) | 1/3669 (0%) | ||
| Lymphoma | 1/3707 (0%) | 0/3669 (0%) | ||
| Malignant melanoma | 0/3707 (0%) | 1/3669 (0%) | ||
| Metastases to bone | 0/3707 (0%) | 1/3669 (0%) | ||
| Metastases to central nervous system | 1/3707 (0%) | 1/3669 (0%) | ||
| Metastases to liver | 0/3707 (0%) | 3/3669 (0.1%) | ||
| Metastases to lung | 0/3707 (0%) | 1/3669 (0%) | ||
| Metastases to lymph nodes | 0/3707 (0%) | 1/3669 (0%) | ||
| Metastases to peritoneum | 1/3707 (0%) | 0/3669 (0%) | ||
| Metastases to retroperitoneum | 0/3707 (0%) | 1/3669 (0%) | ||
| Metastasis | 1/3707 (0%) | 0/3669 (0%) | ||
| Metastatic carcinoid tumour | 0/3707 (0%) | 1/3669 (0%) | ||
| Metastatic gastric cancer | 1/3707 (0%) | 0/3669 (0%) | ||
| Neoplasm malignant | 2/3707 (0.1%) | 0/3669 (0%) | ||
| Non-small cell lung cancer | 2/3707 (0.1%) | 3/3669 (0.1%) | ||
| Oral papilloma | 1/3707 (0%) | 0/3669 (0%) | ||
| Pancreatic carcinoma | 2/3707 (0.1%) | 2/3669 (0.1%) | ||
| Pancreatic carcinoma metastatic | 1/3707 (0%) | 1/3669 (0%) | ||
| Pancreatic neoplasm | 0/3707 (0%) | 1/3669 (0%) | ||
| Paraneoplastic syndrome | 0/3707 (0%) | 1/3669 (0%) | ||
| Pharyngeal cancer stage unspecified | 1/3707 (0%) | 0/3669 (0%) | ||
| Pleural mesothelioma | 1/3707 (0%) | 0/3669 (0%) | ||
| Prostate cancer | 2/3707 (0.1%) | 2/3669 (0.1%) | ||
| Prostatic adenoma | 1/3707 (0%) | 0/3669 (0%) | ||
| Rectal cancer | 0/3707 (0%) | 1/3669 (0%) | ||
| Renal neoplasm | 1/3707 (0%) | 1/3669 (0%) | ||
| Salivary gland cancer | 1/3707 (0%) | 0/3669 (0%) | ||
| Small cell lung cancer stage unspecified | 2/3707 (0.1%) | 0/3669 (0%) | ||
| Tongue neoplasm malignant stage unspecified | 1/3707 (0%) | 0/3669 (0%) | ||
| Tonsil cancer | 0/3707 (0%) | 1/3669 (0%) | ||
| Nervous system disorders | ||||
| Axonal neuropathy | 0/3707 (0%) | 1/3669 (0%) | ||
| Brain oedema | 2/3707 (0.1%) | 3/3669 (0.1%) | ||
| Carotid artery stenosis | 1/3707 (0%) | 1/3669 (0%) | ||
| Cerebral circulatory failure | 1/3707 (0%) | 0/3669 (0%) | ||
| Cerebral haematoma | 0/3707 (0%) | 1/3669 (0%) | ||
| Cerebral haemorrhage | 1/3707 (0%) | 1/3669 (0%) | ||
| Cerebral ischaemia | 2/3707 (0.1%) | 0/3669 (0%) | ||
| Cerebrovascular accident | 3/3707 (0.1%) | 9/3669 (0.2%) | ||
| Cervical root pain | 0/3707 (0%) | 1/3669 (0%) | ||
| Coma | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Convulsion | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Diabetic ketoacidotic hyperglycaemic coma | 1/3707 (0%) | 0/3669 (0%) | ||
| Dizziness | 1/3707 (0%) | 0/3669 (0%) | ||
| Encephalopathy | 1/3707 (0%) | 0/3669 (0%) | ||
| Epilepsy | 1/3707 (0%) | 0/3669 (0%) | ||
| Headache | 0/3707 (0%) | 1/3669 (0%) | ||
| Hypercapnic encephalopathy | 0/3707 (0%) | 1/3669 (0%) | ||
| Ischaemic stroke | 3/3707 (0.1%) | 2/3669 (0.1%) | ||
| Neuralgia | 0/3707 (0%) | 1/3669 (0%) | ||
| Paresis | 1/3707 (0%) | 0/3669 (0%) | ||
| Polyneuropathy | 1/3707 (0%) | 1/3669 (0%) | ||
| Postictal state | 0/3707 (0%) | 1/3669 (0%) | ||
| Sciatica | 1/3707 (0%) | 1/3669 (0%) | ||
| Subarachnoid haemorrhage | 1/3707 (0%) | 1/3669 (0%) | ||
| Syncope | 5/3707 (0.1%) | 2/3669 (0.1%) | ||
| Transient ischaemic attack | 3/3707 (0.1%) | 2/3669 (0.1%) | ||
| Psychiatric disorders | ||||
| Alcohol abuse | 0/3707 (0%) | 1/3669 (0%) | ||
| Alcoholism | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Completed suicide | 1/3707 (0%) | 1/3669 (0%) | ||
| Confusional state | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Delirium tremens | 0/3707 (0%) | 1/3669 (0%) | ||
| Depression | 3/3707 (0.1%) | 3/3669 (0.1%) | ||
| Drug abuse | 1/3707 (0%) | 0/3669 (0%) | ||
| Renal and urinary disorders | ||||
| Glomerulonephritis chronic | 1/3707 (0%) | 0/3669 (0%) | ||
| Haematuria | 0/3707 (0%) | 1/3669 (0%) | ||
| Nephropathy | 0/3707 (0%) | 1/3669 (0%) | ||
| Renal failure | 4/3707 (0.1%) | 1/3669 (0%) | ||
| Renal failure acute | 3/3707 (0.1%) | 1/3669 (0%) | ||
| Urinary retention | 4/3707 (0.1%) | 0/3669 (0%) | ||
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 1/3707 (0%) | 1/3669 (0%) | ||
| Epididymitis | 0/3707 (0%) | 1/3669 (0%) | ||
| Prostatitis | 1/3707 (0%) | 1/3669 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 0/3707 (0%) | 1/3669 (0%) | ||
| Acute respiratory failure | 1/3707 (0%) | 4/3669 (0.1%) | ||
| Allergic granulomatous angiitis | 1/3707 (0%) | 0/3669 (0%) | ||
| Aspiration | 0/3707 (0%) | 1/3669 (0%) | ||
| Atelectasis | 1/3707 (0%) | 0/3669 (0%) | ||
| Bronchopneumopathy | 1/3707 (0%) | 0/3669 (0%) | ||
| Bronchostenosis | 0/3707 (0%) | 1/3669 (0%) | ||
| Bullous lung disease | 1/3707 (0%) | 3/3669 (0.1%) | ||
| Chronic obstructive pulmonary disease | 270/3707 (7.3%) | 335/3669 (9.1%) | ||
| Chronic respiratory failure | 2/3707 (0.1%) | 1/3669 (0%) | ||
| Dyspnoea | 1/3707 (0%) | 5/3669 (0.1%) | ||
| Eosinophilic pneumonia | 0/3707 (0%) | 1/3669 (0%) | ||
| Epistaxis | 1/3707 (0%) | 2/3669 (0.1%) | ||
| Haemoptysis | 4/3707 (0.1%) | 1/3669 (0%) | ||
| Haemothorax | 3/3707 (0.1%) | 0/3669 (0%) | ||
| Hydrothorax | 1/3707 (0%) | 2/3669 (0.1%) | ||
| Hypoxia | 0/3707 (0%) | 1/3669 (0%) | ||
| Lung infiltration | 1/3707 (0%) | 0/3669 (0%) | ||
| Nasal polyps | 0/3707 (0%) | 1/3669 (0%) | ||
| Oropharyngeal swelling | 0/3707 (0%) | 1/3669 (0%) | ||
| Pleural effusion | 3/3707 (0.1%) | 1/3669 (0%) | ||
| Pleurisy | 1/3707 (0%) | 1/3669 (0%) | ||
| Pneumothorax | 3/3707 (0.1%) | 5/3669 (0.1%) | ||
| Pulmonary artery thrombosis | 2/3707 (0.1%) | 0/3669 (0%) | ||
| Pulmonary embolism | 7/3707 (0.2%) | 6/3669 (0.2%) | ||
| Pulmonary fibrosis | 1/3707 (0%) | 0/3669 (0%) | ||
| Pulmonary granuloma | 1/3707 (0%) | 0/3669 (0%) | ||
| Pulmonary hypertension | 1/3707 (0%) | 3/3669 (0.1%) | ||
| Pulmonary oedema | 1/3707 (0%) | 0/3669 (0%) | ||
| Respiratory arrest | 0/3707 (0%) | 1/3669 (0%) | ||
| Respiratory disorder | 0/3707 (0%) | 1/3669 (0%) | ||
| Respiratory failure | 16/3707 (0.4%) | 20/3669 (0.5%) | ||
| Throat lesion | 1/3707 (0%) | 0/3669 (0%) | ||
| Vasomotor rhinitis | 1/3707 (0%) | 0/3669 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Actinic keratosis | 1/3707 (0%) | 0/3669 (0%) | ||
| Drug eruption | 1/3707 (0%) | 0/3669 (0%) | ||
| Psoriasis | 1/3707 (0%) | 0/3669 (0%) | ||
| Seborrhoeic dermatitis | 1/3707 (0%) | 0/3669 (0%) | ||
| Skin ulcer | 0/3707 (0%) | 2/3669 (0.1%) | ||
| Social circumstances | ||||
| Social problem | 1/3707 (0%) | 0/3669 (0%) | ||
| Surgical and medical procedures | ||||
| Alcohol detoxification | 0/3707 (0%) | 1/3669 (0%) | ||
| Intraocular lens implant | 1/3707 (0%) | 0/3669 (0%) | ||
| Surgery | 1/3707 (0%) | 0/3669 (0%) | ||
| Vocal cord polypectomy | 0/3707 (0%) | 1/3669 (0%) | ||
| Vascular disorders | ||||
| Aortic aneurysm | 2/3707 (0.1%) | 4/3669 (0.1%) | ||
| Aortic dissection | 1/3707 (0%) | 1/3669 (0%) | ||
| Aortic stenosis | 1/3707 (0%) | 0/3669 (0%) | ||
| Arteriosclerosis | 3/3707 (0.1%) | 3/3669 (0.1%) | ||
| Arteriosclerosis obliterans | 1/3707 (0%) | 2/3669 (0.1%) | ||
| Arteriovenous fistula | 1/3707 (0%) | 0/3669 (0%) | ||
| Circulatory collapse | 5/3707 (0.1%) | 1/3669 (0%) | ||
| Deep vein thrombosis | 5/3707 (0.1%) | 1/3669 (0%) | ||
| Embolism | 0/3707 (0%) | 1/3669 (0%) | ||
| Femoral artery occlusion | 0/3707 (0%) | 1/3669 (0%) | ||
| Haematoma | 1/3707 (0%) | 0/3669 (0%) | ||
| Hypertension | 9/3707 (0.2%) | 5/3669 (0.1%) | ||
| Hypertensive crisis | 3/3707 (0.1%) | 4/3669 (0.1%) | ||
| Hypotension | 1/3707 (0%) | 0/3669 (0%) | ||
| Iliac artery occlusion | 1/3707 (0%) | 1/3669 (0%) | ||
| Peripheral arterial occlusive disease | 4/3707 (0.1%) | 2/3669 (0.1%) | ||
| Peripheral embolism | 0/3707 (0%) | 1/3669 (0%) | ||
| Peripheral ischaemia | 1/3707 (0%) | 0/3669 (0%) | ||
| Superior vena caval occlusion | 1/3707 (0%) | 0/3669 (0%) | ||
| Vascular occlusion | 1/3707 (0%) | 0/3669 (0%) | ||
| Venous thrombosis | 0/3707 (0%) | 1/3669 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Tiotropium | Salmeterol | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 495/3707 (13.4%) | 581/3669 (15.8%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic obstructive pulmonary disease | 495/3707 (13.4%) | 581/3669 (15.8%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
Results Point of Contact
| Name/Title | Boehringer Ingelheim Call Center |
|---|---|
| Organization | Boehringer Ingelheim Pharmaceuticals |
| Phone | 1-800-243-0127 |
| clintriage.rdg@boehringer-ingelheim.com |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00563381
Other Study ID Numbers:
- 205.389
- EUDRACT2007-001840-33
First Posted:
Nov 26, 2007
Last Update Posted:
Dec 24, 2013
Last Verified:
Jul 1, 2012