Inhaled Corticosteroid Withdrawal in Patients With Chronic Obstructive Pulmonary Disease

Phase 4

Completed

Conditions: Pulmonary Disease, Chronic Obstructive

Interventions: Drug: tiotropium inhalation
Drug: salmeterol xinafoate
Drug: fluticasone propionate
Drug: placebo matched for fluticasone propionate

Registration Number: NCT00975195

Lead Sponsor: Boehringer Ingelheim

Brief Summary: This is a randomised study to be conducted in patients with severe to very severe Chronic Obstructive Pulmonary Disease (COPD) to establish whether there is a need for these patients to be continuously treated with an inhaled corticosteroid on top of two potent long-acting bronchodilators. The study also aims to identify the type of patients who are likely to benefit from inhaled corticosteroid maintenance therapy.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2488

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
fluticasone high dose	salmeterol xinafoate	fluticasone priopionate high dose and tiotropium inhalation and salmeterol xinafoate
fluticasone high dose	tiotropium inhalation	fluticasone priopionate high dose and tiotropium inhalation and salmeterol xinafoate
fluticasone medium & low doses	tiotropium inhalation	fluticasone priopionate medium and high doses; and tiotropium inhalation; and salmeterol xinafoate; and placebo matched to fluticasone priopionate
fluticasone medium & low doses	salmeterol xinafoate	fluticasone priopionate medium and high doses; and tiotropium inhalation; and salmeterol xinafoate; and placebo matched to fluticasone priopionate
fluticasone medium & low doses	placebo matched for fluticasone propionate	fluticasone priopionate medium and high doses; and tiotropium inhalation; and salmeterol xinafoate; and placebo matched to fluticasone priopionate
fluticasone medium & low doses	fluticasone propionate	fluticasone priopionate medium and high doses; and tiotropium inhalation; and salmeterol xinafoate; and placebo matched to fluticasone priopionate
fluticasone high dose	fluticasone propionate	fluticasone priopionate high dose and tiotropium inhalation and salmeterol xinafoate

Primary Outcome Measures

Name	Time	Method
Time to First Moderate or Severe On-treatment COPD Exacerbation	During randomised treatment, up to 488 days	A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as an increase or new onset of ≥2 lower respiratory symptoms related to COPD, with ≥1 symptom lasting ≥3 days, requiring a change in treatment. Lower respiratory symptoms included shortness of breath, sputum production (volume), sputum purulence, cough, wheezing and chest tightness. A change in treatment included: hospitalisation/treatment in an urgent care unit, prescription of antibiotics and/or systemic steroids or a significant change of prescribed respiratory medication such as theophyllines, long-acting beta-agonists or inhaled corticosteroids. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital.The "measure type" displays the 25th percentile and its 95% confidence interval.

Secondary Outcome Measures

Name	Time	Method
Proportion of Patients With ≥1 Moderate or Severe On-treatment COPD Exacerbation	During randomised treatment, up to 488 days	Presence (yes vs no) of at least one moderate or severe on-treatment COPD exacerbation, displayed as a percentage. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. Exacerbations were considered moderate if they required prescription of antibiotics and/or systemic steroids.
Proportion of Patients With at Least One Severe On-treatment COPD Exacerbation.	During randomised treatment, up to 488 days	Presence (yes vs no) of at least one severe on-treatment COPD exacerbation, displayed as a percentage. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital.
Number of On-treatment COPD Exacerbations	During randomised treatment, up to 488 days	Number of on-treatment COPD exacerbations of any severity, based on a 7-day gap rule: exacerbations where the onset date of the second exacerbation event was ≤7 days after the end date of the first exacerbation event were combined. Measured values show adjusted event rate.
Severity of On-treatment COPD Exacerbations	During randomised treatment, up to 488 days	Severity of on-treatment COPD exacerbations: for each patient, the worst applicable category was taken (i.e. none, mild, moderate or severe)
Changes in On-treatment Dyspnoea as Measured by the Modified Medical Research Council (MMRC) Dyspnoea Scale	Baseline and week 18 and 52 visits	Change from baseline in on-treatment dyspnoea as measured by the Modified Medical Research Council (MMRC) dyspnoea scale; change was calculated as week score minus baseline score. Negative changes from baseline indicate an improvement in health. Scale from 0 to 4: * 0 = not troubled by breathlessness, except during strenuous exercise * 1 = short of breath when hurrying or walking up a slight hill * 2 = walks slower than contemporaries on the same level because of breathlessness, or has to stop for breath when walking at own pace * 3 = stops for breath after approximately 100 yards, or after a few minutes on the level * 4 = too breathless to leave the house, or breathless when dressing or undressing "No breathlessness" was given a score of -1 Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Number of Moderate or Severe On-treatment COPD Exacerbations	During randomised treatment, up to 488 days	Number of moderate or severe on-treatment COPD exacerbations, based on a 7-day gap rule: exacerbations where the onset date of the second exacerbation event was ≤7 days after the end date of the first exacerbation event were combined and counted as moderate or severe if ≥1 of the contributing exacerbation events was moderate or severe. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. Exacerbations were considered moderate if they required prescription of antibiotics and/or systemic steroids. Measured values show adjusted mean event rate.
Time to First On-treatment COPD Exacerbation	During randomised treatment, up to 488 days	Time to first on-treatment COPD exacerbation of any severity. The "measure type" displays the 25th percentile and its 95% confidence interval.
Change in On-treatment Physical Health Status as Determined by Body Mass Index (BMI)	Baseline and week 18 and 52 visits	Change from baseline in on-treatment physical health status as determined by body mass index (BMI); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Change in On-treatment Lung Function as Measured by Trough FEV1	Baseline and week 6, 12, 18 and 52 visits	Change from baseline in on-treatment lung function as measured by trough forced expiratory volume in one second (FEV1); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Impact Domain	Baseline and week 12, 18 and 52 visits	Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Cough impact domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from "not at all/never" to "extremely/always" on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less impact due to cough. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Symptoms Domain	Baseline and week 12, 18 and 52 visits	Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Sputum symptoms domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from "not at all/never" to "extremely/always" on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less symptoms due to sputum. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time to First Severe On-treatment COPD Exacerbation	During randomised treatment, up to 488 days	Time to first severe on-treatment COPD exacerbation. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. The "measure type" displays the 25th percentile and its 95% confidence interval.
Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Impact Domain	Baseline and week 27 and 52 visits	Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Impact Domain. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Symptoms Domain	Baseline and week 27 and 52 visits	Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Symptoms domain. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Number of Severe On-treatment COPD Exacerbations	During randomised treatment, up to 488 days	Number of severe on-treatment COPD exacerbations based on a 7-day gap rule: exacerbations where the onset date of the second exacerbation event was ≤7 days after the end date of the first exacerbation event were combined and counted as severe if ≥1 of the contributing exacerbation events was severe. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. Measured values show adjusted event rate.
Proportion of Patients With at Least One On-treatment COPD Exacerbation	During randomised treatment, up to 488 days	Presence (yes vs no) of at least one on-treatment COPD exacerbation of any severity, displayed as a percentage.
Change in On-treatment BODE Index	Baseline and week 18 and 52 visits	Change from baseline in on-treatment BODE index (Body mass index, airflow Obstruction, Dyspnea and Exercise capacity index), a composite score ranging from 0 (best) to 10 (worst); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Impact Domain	Baseline and week 12, 18 and 52 visits	Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Sputum impact domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from "not at all/never" to "a lot/always" on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less impact due to sputum. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Change in On-treatment FVC as Measured by Home Based Spirometry	Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits	Change from baseline in on-treatment forced vital capacity (FVC) as measured by home based spirometry. Change was calculated as week score minus baseline score. The weekly mean was defined as the mean of the measurements taken during the last 7 days prior to the visit date, and was calculated if ≥4 of the 7 days had non-missing measurements. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Change in On-treatment PEFR as Measured by Home Based Spirometry	Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits	Change from baseline in on-treatment peak expiratory flow rate (PEFR) as measured by home based spirometry; change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Change in On-treatment Physician Global Evaluation	Baseline and week 27 and 52 visits	Change from baseline in on-treatment physician global evaluation. The evaluation reflected the physician's opinion of the patient's overall condition and was based on the need for concomitant medication, the number and severity of exacerbations, the severity of cough, the ability to exercise, the amount of wheezing and any other relevant clinical observations. Patients were graded on a scale of 1 (poor) to 8 (excellent). Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Change in On-treatment Exercise Capacity Measured by Six-minute Walk Test (6-MWT)	Baseline and week 18 and 52 visits	Change from baseline in on-treatment exercise capacity measured by six-minute walk test (6-MWT); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Symptoms Domain	Baseline and week 12, 18 and 52 visits	Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Cough symptoms domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from "not at all/never" to "a lot/always" on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less symptoms due to cough. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Change in On-treatment FEV1 as Measured by Home Based Spirometry	Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits	Change from baseline in on-treatment Forced Expiratory Volume in One Second (FEV1) as measured by home based spirometry. Change was calculated as week score minus baseline score. The weekly mean was defined as the mean of the measurements taken during the last 7 days prior to the visit date, and was calculated if ≥4 of the 7 days had non-missing measurements. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Activity Domain	Baseline and week 27 and 52 visits	Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Activity domain. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Total Score	Baseline and week 27 and 52 visits	Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Total score. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.

Trial Locations

Locations (222): 352.2046.36004 Boehringer Ingelheim Investigational Site
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Komarom, Hungary
352.2046.36001 Boehringer Ingelheim Investigational Site
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Szarvas, Hungary
352.2046.36006 Boehringer Ingelheim Investigational Site
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Pecs, Hungary
352.2046.64006 Boehringer Ingelheim Investigational Site
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Hamilton, New Zealand
352.2046.64001 Boehringer Ingelheim Investigational Site
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Newtown Wellington NZ, New Zealand
352.2046.07009 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation
352.2046.2165A Boehringer Ingelheim Investigational Site
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Sfax, Tunisia
352.2046.88604 Boehringer Ingelheim Investigational Site
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Taichung, Taiwan
352.2046.63009 Boehringer Ingelheim Investigational Site
🇵🇭
Muntinlupa, Philippines
352.2046.07001 Boehringer Ingelheim Investigational Site
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St. Petersburg, Russian Federation
352.2046.35906 Boehringer Ingelheim Investigational Site
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Sofia, Bulgaria
352.2046.55006 Boehringer Ingelheim Investigational Site
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Porto Alegre, Brazil
352.2046.86006 Boehringer Ingelheim Investigational Site
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Beijing, China
352.2046.32004 Boehringer Ingelheim Investigational Site
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Middelheim, Belgium
352.2046.86001 Boehringer Ingelheim Investigational Site
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Guangzhou, China
352.2046.86004 Boehringer Ingelheim Investigational Site
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Shanghai, China
352.2046.86003 Boehringer Ingelheim Investigational Site
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Beijing, China
352.2046.3317A Boehringer Ingelheim Investigational Site
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Brest, France
352.2046.3301A Boehringer Ingelheim Investigational Site
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Marseille cedex 20, France
352.2046.3325A Boehringer Ingelheim Investigational Site
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Nantes Cedex 1, France
352.2046.3317C Boehringer Ingelheim Investigational Site
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Brest, France
352.2046.3333A Boehringer Ingelheim Investigational Site
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Marseille, France
352.2046.35904 Boehringer Ingelheim Investigational Site
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Sofia, Bulgaria
352.2046.35907 Boehringer Ingelheim Investigational Site
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Sofia, Bulgaria
352.2046.35908 Boehringer Ingelheim Investigational Site
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Sofia, Bulgaria
352.2046.30011 Boehringer Ingelheim Investigational Site
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Athens, Greece
352.2046.39003 Boehringer Ingelheim Investigational Site
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Modena, Italy
352.2046.39008 Boehringer Ingelheim Investigational Site
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Tradate (va), Italy
352.2046.3326A Boehringer Ingelheim Investigational Site
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Montpellier, France
352.2046.35902 Boehringer Ingelheim Investigational Site
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Rousse, Bulgaria
352.2046.35909 Boehringer Ingelheim Investigational Site
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Veliko Tarnovo, Bulgaria
352.2046.64007 Boehringer Ingelheim Investigational Site
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Auckland NZ, New Zealand
352.2046.36011 Boehringer Ingelheim Investigational Site
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Szigetszentmiklos, Hungary
352.2046.3320B Boehringer Ingelheim Investigational Site
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Castelnau le Lez, France
352.2046.35903 Boehringer Ingelheim Investigational Site
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Stara Zagora, Bulgaria
352.2046.55005 Boehringer Ingelheim Investigational Site
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Goiania, Brazil
352.2046.3320A Boehringer Ingelheim Investigational Site
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Castelnau le Lez, France
352.2046.55003 Boehringer Ingelheim Investigational Site
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Sao Paulo, Brazil
352.2046.49002 Boehringer Ingelheim Investigational Site
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Donaustauf, Germany
352.2046.49020 Boehringer Ingelheim Investigational Site
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Berlin, Germany
352.2046.49021 Boehringer Ingelheim Investigational Site
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Berlin, Germany
352.2046.35905 Boehringer Ingelheim Investigational Site
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Bourgas, Bulgaria
352.2046.3332A Boehringer Ingelheim Investigational Site
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Nîmes, France
352.2046.3332B Boehringer Ingelheim Investigational Site
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Nîmes, France
352.2046.55002 Boehringer Ingelheim Investigational Site
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Goiânia, Brazil
352.2046.3317B Boehringer Ingelheim Investigational Site
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Brest, France
352.2046.49024 Boehringer Ingelheim Investigational Site
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Geesthacht, Germany
352.2046.39001 Boehringer Ingelheim Investigational Site
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Pisa, Italy
352.2046.49013 Boehringer Ingelheim Investigational Site
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Frankfurt, Germany
352.2046.36003 Boehringer Ingelheim Investigational Site
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Cegled, Hungary
352.2046.3320C Boehringer Ingelheim Investigational Site
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Castelnau le Lez, France
352.2046.3335A Boehringer Ingelheim Investigational Site
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Clermont Ferrand cedex 1, France
352.2046.3332C Boehringer Ingelheim Investigational Site
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Nîmes, France
352.2046.63006 Boehringer Ingelheim Investigational Site
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Quezon City, Philippines
352.2046.30003 Boehringer Ingelheim Investigational Site
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Athens, Greece
352.2046.39002 Boehringer Ingelheim Investigational Site
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Catania, Italy
352.2046.3324A Boehringer Ingelheim Investigational Site
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Nîmes, France
352.2046.3326C Boehringer Ingelheim Investigational Site
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Montpellier, France
352.2046.36005 Boehringer Ingelheim Investigational Site
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Szazhalombatta, Hungary
352.2046.3325D Boehringer Ingelheim Investigational Site
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Nantes Cedex 1, France
352.2046.3331A Boehringer Ingelheim Investigational Site
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Perpignan, France
352.2046.49008 Boehringer Ingelheim Investigational Site
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Bochum, Germany
352.2046.49001 Boehringer Ingelheim Investigational Site
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Großhansdorf, Germany
352.2046.64002 Boehringer Ingelheim Investigational Site
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Tauranga, New Zealand
352.2046.39005 Boehringer Ingelheim Investigational Site
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Foggia, Italy
352.2046.63001 Boehringer Ingelheim Investigational Site
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Caloocan, Philippines
352.2046.48006 Boehringer Ingelheim Investigational Site
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Bytom, Poland
352.2046.48003 Boehringer Ingelheim Investigational Site
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Ostrow Wielkopolska, Poland
352.2046.49019 Boehringer Ingelheim Investigational Site
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Cottbus, Germany
352.2046.49023 Boehringer Ingelheim Investigational Site
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Frankfurt/Main, Germany
352.2046.3302B Boehringer Ingelheim Investigational Site
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Saint-Pierre cedex, France
352.2046.49012 Boehringer Ingelheim Investigational Site
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Berlin, Germany
352.2046.3331B Boehringer Ingelheim Investigational Site
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Perpignan, France
352.2046.39007 Boehringer Ingelheim Investigational Site
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Cona, Italy
352.2046.39006 Boehringer Ingelheim Investigational Site
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Montescano (pv), Italy
352.2046.39004 Boehringer Ingelheim Investigational Site
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Sesto S. Giovanni (mi), Italy
352.2046.07008 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation
352.2046.36002 Boehringer Ingelheim Investigational Site
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Deszk, Hungary
352.2046.49005 Boehringer Ingelheim Investigational Site
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Marburg, Germany
352.2046.64005 Boehringer Ingelheim Investigational Site
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Otahuhu New Zealand, New Zealand
352.2046.64004 Boehringer Ingelheim Investigational Site
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Dunedin, New Zealand
352.2046.07006 Boehringer Ingelheim Investigational Site
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Ivanovo, Russian Federation
352.2046.07002 Boehringer Ingelheim Investigational Site
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Samara, Russian Federation
352.2046.48007 Boehringer Ingelheim Investigational Site
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Wroclaw, Poland
352.2046.38005 Boehringer Ingelheim Investigational Site
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Vinnitsa, Ukraine
352.2046.90019 Boehringer Ingelheim Investigational Site
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Ankara, Turkey
352.2046.27003 Boehringer Ingelheim Investigational Site
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Cape Town, South Africa
352.2046.64003 Boehringer Ingelheim Investigational Site
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Christchurch, New Zealand
352.2046.44016 Boehringer Ingelheim Investigational Site
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Isleworth, United Kingdom
352.2046.27002 Boehringer Ingelheim Investigational Site
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Bellville, South Africa
352.2046.34011 Boehringer Ingelheim Investigational Site
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Sevilla, Spain
352.2046.44002 Boehringer Ingelheim Investigational Site
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Liverpool, United Kingdom
352.2046.63003 Boehringer Ingelheim Investigational Site
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Manila, Philippines
352.2046.90010 Boehringer Ingelheim Investigational Site
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Denizli, Turkey
352.2046.34006 Boehringer Ingelheim Investigational Site
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Palma de Mallorca, Spain
352.2046.63007 Boehringer Ingelheim Investigational Site
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Quezon, Philippines
352.2046.38007 Boehringer Ingelheim Investigational Site
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Ivano-Frankivsk, Ukraine
352.2046.90008 Boehringer Ingelheim Investigational Site
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Istanbul, Turkey
352.2046.34008 Boehringer Ingelheim Investigational Site
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Badajoz, Spain
352.2046.44012 Boehringer Ingelheim Investigational Site
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Cottingham, Hull, United Kingdom
352.2046.44001 Boehringer Ingelheim Investigational Site
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London, United Kingdom
352.2046.48011 Boehringer Ingelheim Investigational Site
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Tarnowskie Gory, Poland
352.2046.90016 Boehringer Ingelheim Investigational Site
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Bursa, Turkey
352.2046.34002 Boehringer Ingelheim Investigational Site
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Barakaldo (Bilbao), Spain
352.2046.34013 Boehringer Ingelheim Investigational Site
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Salt (Girona), Spain
352.2046.27006 Boehringer Ingelheim Investigational Site
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Amanzimtoti, South Africa
352.2046.27004 Boehringer Ingelheim Investigational Site
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Tygerberg, South Africa
352.2046.34004 Boehringer Ingelheim Investigational Site
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Barcelona, Spain
352.2046.90009 Boehringer Ingelheim Investigational Site
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Ankara, Turkey
352.2046.44008 Boehringer Ingelheim Investigational Site
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Baillieston, Glasgow, United Kingdom
352.2046.34009 Boehringer Ingelheim Investigational Site
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Hospitalet de Llobregat, Spain
352.2046.27001 Boehringer Ingelheim Investigational Site
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Cape Town, South Africa
352.2046.90017 Boehringer Ingelheim Investigational Site
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Istanbul, Turkey
352.2046.38003 Boehringer Ingelheim Investigational Site
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Kharkov, Ukraine
352.2046.38006 Boehringer Ingelheim Investigational Site
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Kiev, Ukraine
352.2046.90014 Boehringer Ingelheim Investigational Site
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Izmir, Turkey
352.2046.90005 Boehringer Ingelheim Investigational Site
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Izmit, Turkey
352.2046.90007 Boehringer Ingelheim Investigational Site
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Kayseri, Turkey
352.2046.44018 Boehringer Ingelheim Investigational Site
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Belfast, United Kingdom
352.2046.44026 Boehringer Ingelheim Investigational Site
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Chertsey, United Kingdom
352.2046.44017 Boehringer Ingelheim Investigational Site
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Norwich, United Kingdom
352.2046.44006 Boehringer Ingelheim Investigational Site
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Chesterfield, United Kingdom
352.2046.44028 Boehringer Ingelheim Investigational Site
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Inverness, United Kingdom
352.2046.44019 Boehringer Ingelheim Investigational Site
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Sunderland, United Kingdom
352.2046.31003 Boehringer Ingelheim Investigational Site
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Rotterdam, Netherlands
352.2046.31004 Boehringer Ingelheim Investigational Site
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Heerlen, Netherlands
352.2046.31001 Boehringer Ingelheim Investigational Site
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Leeuwarden, Netherlands
352.2046.31002 Boehringer Ingelheim Investigational Site
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Veldhoven, Netherlands
352.2046.38001 Boehringer Ingelheim Investigational Site
🇺🇦
Vinnytsya, Ukraine
352.2046.30004 Boehringer Ingelheim Investigational Site
🇬🇷
Athens, Greece
352.2046.30005 Boehringer Ingelheim Investigational Site
🇬🇷
Athens, Greece
352.2046.30007 Boehringer Ingelheim Investigational Site
🇬🇷
Athens, Greece
352.2046.30008 Boehringer Ingelheim Investigational Site
🇬🇷
Athens, Greece
352.2046.30012 Boehringer Ingelheim Investigational Site
🇬🇷
Athens, Greece
352.2046.30009 Boehringer Ingelheim Investigational Site
🇬🇷
Larisa, Greece
352.2046.30001 Boehringer Ingelheim Investigational Site
🇬🇷
Thessaloniki, Greece
352.2046.30002 Boehringer Ingelheim Investigational Site
🇬🇷
Thessaloniki, Greece
352.2046.32017 Boehringer Ingelheim Investigational Site
🇧🇪
Gilly, Belgium
352.2046.32014 Boehringer Ingelheim Investigational Site
🇧🇪
Herentals, Belgium
352.2046.32010 Boehringer Ingelheim Investigational Site
🇧🇪
Montigny-le-Tilleul, Belgium
352.2046.32013 Boehringer Ingelheim Investigational Site
🇧🇪
Turnhout, Belgium
352.2046.45001 Boehringer Ingelheim Investigational Site
🇩🇰
Aarhus C, Denmark
352.2046.45003 Boehringer Ingelheim Investigational Site
🇩🇰
København NV, Denmark
352.2046.45002 Boehringer Ingelheim Investigational Site
🇩🇰
Odense C, Denmark
352.2046.86008 Boehringer Ingelheim Investigational Site
🇨🇳
Chongqing, China
352.2046.86005 Boehringer Ingelheim Investigational Site
🇨🇳
Shanghai, China
352.2046.86007 Boehringer Ingelheim Investigational Site
🇨🇳
Wuhan, China
352.2046.86002 Boehringer Ingelheim Investigational Site
🇨🇳
Beijing, China
352.2046.44010 Boehringer Ingelheim Investigational Site
🇬🇧
Birmingham, United Kingdom
352.2046.44021 Boehringer Ingelheim Investigational Site
🇬🇧
Sheffield, United Kingdom
352.2046.3334A Boehringer Ingelheim Investigational Site
🇫🇷
Nantes, France
352.2046.3331C Boehringer Ingelheim Investigational Site
🇫🇷
Perpignan, France
352.2046.3329A Boehringer Ingelheim Investigational Site
🇫🇷
Saint Laurent du Var, France
352.2046.3329B Boehringer Ingelheim Investigational Site
🇫🇷
Saint Laurent du Var, France
352.2046.3302A Boehringer Ingelheim Investigational Site
🇫🇷
Saint-Pierre cedex, France
352.2046.3302C Boehringer Ingelheim Investigational Site
🇫🇷
Saint-Pierre cedex, France
352.2046.3336A Boehringer Ingelheim Investigational Site
🇫🇷
Toulouse cedex 9, France
352.2046.3336C Boehringer Ingelheim Investigational Site
🇫🇷
Toulouse cedex 9, France
352.2046.3336B Boehringer Ingelheim Investigational Site
🇫🇷
Toulouse cedex 9, France
352.2046.3337A Boehringer Ingelheim Investigational Site
🇫🇷
Toulouse, France
352.2046.90003 Boehringer Ingelheim Investigational Site
🇹🇷
Istanbul, Turkey
352.2046.90004 Boehringer Ingelheim Investigational Site
🇹🇷
Istanbul, Turkey
352.2046.90006 Boehringer Ingelheim Investigational Site
🇹🇷
Istanbul, Turkey
352.2046.90011 Boehringer Ingelheim Investigational Site
🇹🇷
Izmir, Turkey
352.2046.90018 Boehringer Ingelheim Investigational Site
🇹🇷
Izmir, Turkey
352.2046.90001 Boehringer Ingelheim Investigational Site
🇹🇷
Mersin, Turkey
352.2046.90002 Boehringer Ingelheim Investigational Site
🇹🇷
Samsun, Turkey
352.2046.55001 Boehringer Ingelheim Investigational Site
🇧🇷
Porto Alegre, Brazil
352.2046.49025 Boehringer Ingelheim Investigational Site
🇩🇪
Frankfurt, Germany
352.2046.49022 Boehringer Ingelheim Investigational Site
🇩🇪
Gelnhausen, Germany
352.2046.49006 Boehringer Ingelheim Investigational Site
🇩🇪
Heidelberg, Germany
352.2046.49014 Boehringer Ingelheim Investigational Site
🇩🇪
Immenhausen, Germany
352.2046.49004 Boehringer Ingelheim Investigational Site
🇩🇪
Mainz, Germany
352.2046.61006 Boehringer Ingelheim Investigational Site
🇦🇺
Concord, New South Wales, Australia
352.2046.61001 Boehringer Ingelheim Investigational Site
🇦🇺
Glebe, New South Wales, Australia
352.2046.61002 Boehringer Ingelheim Investigational Site
🇦🇺
Westmead, New South Wales, Australia
352.2046.61004 Boehringer Ingelheim Investigational Site
🇦🇺
Daw Park, South Australia, Australia
352.2046.61003 Boehringer Ingelheim Investigational Site
🇦🇺
Toorak Gardens, South Australia, Australia
352.2046.61005 Boehringer Ingelheim Investigational Site
🇦🇺
Woodville, South Australia, Australia
352.2046.3314A Boehringer Ingelheim Investigational Site
🇫🇷
Forbach, France
352.2046.44003 Boehringer Ingelheim Investigational Site
🇬🇧
Cambridge, United Kingdom
352.2046.88606 Boehringer Ingelheim Investigational Site
🇨🇳
Kaohsiung, Taiwan
352.2046.3325C Boehringer Ingelheim Investigational Site
🇫🇷
Nantes Cedex 1, France
352.2046.3302D Boehringer Ingelheim Investigational Site
🇫🇷
Saint-Pierre cedex, France
352.2046.30006 Boehringer Ingelheim Investigational Site
🇬🇷
Heraklion, Greece
352.2046.49003 Boehringer Ingelheim Investigational Site
🇩🇪
Köln, Germany
352.2046.49016 Boehringer Ingelheim Investigational Site
🇩🇪
Kiel, Germany
352.2046.49015 Boehringer Ingelheim Investigational Site
🇩🇪
München, Germany
352.2046.63004 Boehringer Ingelheim Investigational Site
🇵🇭
Manila, Philippines
352.2046.07011 Boehringer Ingelheim Investigational Site
🇷🇺
Ekaterinburg, Russian Federation
352.2046.07003 Boehringer Ingelheim Investigational Site
🇷🇺
Saratov, Russian Federation
352.2046.07004 Boehringer Ingelheim Investigational Site
🇷🇺
Yaroslavl, Russian Federation
352.2046.07005 Boehringer Ingelheim Investigational Site
🇷🇺
Yaroslavl, Russian Federation
352.2046.27007 Boehringer Ingelheim Investigational Site
🇿🇦
Pretoria, South Africa
352.2046.27005 Boehringer Ingelheim Investigational Site
🇿🇦
Somerset West, South Africa
352.2046.34010 Boehringer Ingelheim Investigational Site
🇪🇸
Pozuelo de Alarcón, Spain
352.2046.34001 Boehringer Ingelheim Investigational Site
🇪🇸
Barcelona, Spain
352.2046.2162A Boehringer Ingelheim Investigational Site
🇹🇳
Ariana, Tunisia
352.2046.88603 Boehringer Ingelheim Investigational Site
🇨🇳
Taipei, Taiwan
352.2046.2163A Boehringer Ingelheim Investigational Site
🇹🇳
Tunis, Tunisia
352.2046.90012 Boehringer Ingelheim Investigational Site
🇹🇷
Istanbul, Turkey
352.2046.38002 Boehringer Ingelheim Investigational Site
🇺🇦
Kharkiv, Ukraine
352.2046.44009 Boehringer Ingelheim Investigational Site
🇬🇧
Barnsley, United Kingdom
352.2046.44025 Boehringer Ingelheim Investigational Site
🇬🇧
Windsor, United Kingdom
352.2046.48002 Boehringer Ingelheim Investigational Site
🇵🇱
Poznan, Poland
352.2046.48009 Boehringer Ingelheim Investigational Site
🇵🇱
Rzeszow, Poland
352.2046.48005 Boehringer Ingelheim Investigational Site
🇵🇱
Warsaw, Poland
352.2046.88601 Boehringer Ingelheim Investigational Site
🇨🇳
Taipei, Taiwan
352.2046.63008 Boehringer Ingelheim Investigational Site
🇵🇭
Quezon City, Philippines
352.2046.63005 Boehringer Ingelheim Investigational Site
🇵🇭
Quezon, Philippines
352.2046.88608 Boehringer Ingelheim Investigational Site
🇨🇳
Taiwan, Taiwan
352.2046.2164A Boehringer Ingelheim Investigational Site
🇹🇳
Sousse, Tunisia
352.2046.48001 Boehringer Ingelheim Investigational Site
🇵🇱
Poznan, Poland
352.2046.88607 Boehringer Ingelheim Investigational Site
🇨🇳
Taiwan, Taiwan
352.2046.2161A Boehringer Ingelheim Investigational Site
🇹🇳
Ariana, Tunisia
352.2046.38004 Boehringer Ingelheim Investigational Site
🇺🇦
Kiev, Ukraine
352.2046.32001 Boehringer Ingelheim Investigational Site
🇧🇪
Leuven, Belgium
352.2046.32016 Boehringer Ingelheim Investigational Site
🇧🇪
Bruxelles, Belgium
352.2046.32015 Boehringer Ingelheim Investigational Site
🇧🇪
Eupen, Belgium
352.2046.32002 Boehringer Ingelheim Investigational Site
🇧🇪
Bruxelles, Belgium
352.2046.32006 Boehringer Ingelheim Investigational Site
🇧🇪
Jambes, Belgium
352.2046.32008 Boehringer Ingelheim Investigational Site
🇧🇪
Lebbeke, Belgium