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Efficacy and Safety of 2 Doses of Tiotropium Respimat® Compared to Placebo in Children With Severe Persistent Asthma

Phase 3
Completed
Conditions
Asthma
Interventions
Registration Number
NCT01634152
Lead Sponsor
Boehringer Ingelheim
Brief Summary

The overall purpose of the trial is to evaluate efficacy and safety of tiotropium inhalation solution (2.5 mcg and 5 mcg) delivered via Respimat® inhaler once daily in the evening over 12 weeks, compared to placebo, as add-on controller therapy on top of usual care in children (6 to 11 years old) with severe persistent asthma.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
401
Inclusion Criteria

Not provided

Read More
Exclusion Criteria

Not provided

Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo QDPlacebo-
Tiotropium low dose QDTiotropium low dose mcg-
Tiotropium medium dose QDTiotropium high dose-
Primary Outcome Measures
NameTimeMethod
FEV1 Peak(0-3h) Change From BaselineBaseline and 12 weeks

Change from baseline in peak forced expiratory volume in 1 second within the first 3 hours post dosing (FEV1 peak(0-3h)) measured at week 12.

Measured values presented are actually adjusted means.

Secondary Outcome Measures
NameTimeMethod
Trough FEV1 Change From BaselineBaseline and 12 weeks

Change from baseline in Trough (pre-dose) Forced expiratory volume in 1 second (FEV1) measured at week 12.

Measured values presented are actually adjusted means.

FVC Peak(0-3h) Change From BaselineBaseline and 12 weeks

Change from baseline in Maximum forced vital capacity (FVC) measured within the first 3 hours after administration of trial medication (FVC peak(0-3h)) after 12 weeks of treatment.

The measured values presented are actually adjusted means.

Trough FVC Change From BaselineBaseline and 12 weeks

Change from baseline in Trough (pre-dose) FVC measured at week 12.

Measured values presented are actually adjusted means.

FEV1 AUC (0-3h) Change From BaselineBaseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks

Change from baseline of area under the curve (AUC) from 0 to 3 hours for FEV1 (FEV1 AUC (0-3h)) after 12 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h).

Measured values presented are actually adjusted means.

FVC AUC (0-3h) Change From BaselineBaseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks

Change from baseline of area under the curve (AUC) from 0 to 3 hours for FVC (Forced vital capacity) (FVC AUC (0-3h)) after 12 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h).

Measured values presented are actually adjusted means.

FEV1 Change From Baseline at Each Individual TimepointBaseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks

Forced expiratory volume in one second (FEV1) change from baseline at each individual timepoint.

The measured values presented are actually adjusted means.

FVC Change From Baseline at Each Individual TimepointBaseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks

FVC change from baseline at each individual timepoint.

The measured values presented are actually adjusted means.

Control of Asthma as Assessed by ACQ-IA Total ScoreBaseline and 12 weeks

Change from baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) total score measured at week 12.

The ACQ-IA is a scale containing 7 questions. Each question has a 7 point scale which ranges from 0 to 6. A score of 0 corresponds to no impairment and a score of 6 corresponds to maximum impairment. ACQ-IA total score is calculated as the mean of the responses to all 7 questions.

The measured values presented are actually adjusted means.

ACQ-IA Total Score Responders12 weeks

Responder categories based on the ACQ-IA total score after 12 weeks of treatment. Analysis was performed using the following categories and definitions: responder (change from trial baseline ≤-0.5), no change (-0.5 \<change from trial baseline \<0.5) and worsening (change from trial baseline ≥0.5) No statistical testing was performed for ACQ-IA total score responders.

The ACQ-IA is a scale containing 7 questions, each question has a 7-point scale which ranges from 0 to 6; a score of 0 corresponds to no impairment and a score of 6 corresponds to maximum impairment.

Use of PRN Rescue Medication Per DayBaseline and 12 weeks

Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used per day (24 hour period) based on the weekly mean at week 12.

The measured values presented are actually adjusted means.

Use of PRN Rescue Medication During the DaytimeBaseline and 12 weeks

Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during the daytime based on the weekly mean at week 12.

Measured values presented are actually adjusted means.

Use of PRN Rescue Medication During the Night-timeBaseline and 12 weeks

Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during the night-time based on the weekly mean at week 12.

Measured values presented are actually adjusted means

Peak Expiratory Flow (PEF) a.m. Change From BaselineBaseline and 12 weeks

Change from baseline in the morning (a.m.) peak expiratory flow based on the weekly mean at week 12.

Measured values presented are actually adjusted means.

Peak Expiratory Flow (PEF) p.m. Change From BaselineBaseline and 12 weeks

Change from baseline in the evening (p.m.) peak expiratory flow based on the weekly mean at week 12.

Measured values presented are actually adjusted means.

Peak Expiratory Flow (PEF) Variability Change From BaselineBaseline and 12 weeks

Change from baseline in the peak expiratory flow variability based on the weekly mean at week 12.

Measured values presented are actually adjusted means.

FEV1 a.m. Change From BaselineBaseline and 12 weeks

Change from baseline in morning (a.m.) FEV1 based on the weekly mean at week 12.

Measured values presented are actually adjusted means.

FEV1 p.m. Change From BaselineBaseline and 12 weeks

Change from baseline in evening (p.m.) FEV1 based on the weekly mean at week 12.

Measured values presented are actually adjusted means.

Change From Baseline in Nighttime AwakeningsBaseline and 12 weeks

Change from baseline in nighttime awakenings based on the weekly mean at week 12.

Nighttime awakenings was assessed by the question "Did you wake up during the night due to your asthma?" from the e-diary. Scores range from 1 (did not wake up) to 5 (was awake all night).

Measured values presented are actually adjusted means.

Change From Baseline in Morning Asthma SymptomsBaseline and 12 weeks

Change from baseline in morning asthma symptoms based on the weekly mean at week 12.

Morning asthma symptoms was assessed by the question "how were your asthma symptoms this morning?" from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms).

Measured values presented are actually adjusted means.

Change From Baseline in Daytime Asthma SymptomsBaseline and 12 weeks

Change from baseline in daytime asthma symptoms based on the weekly mean at week 12.

Daytime asthma symptoms was assessed by the question "how were your asthma symptoms during the day?" from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms).

Measured values presented are actually adjusted means.

Change From Baseline in Daytime Activity LimitationsBaseline and 12 weeks

Change from baseline in daytime activity limitations based on the weekly mean at week 12.

Daytime activity limitations was assessed by the question "how limited were you in your activities today because of your asthma?" from the e-diary. Scores range from 1 (not limited) to 5 (totally limited).

Measured values presented are actually adjusted means.

Change From Baseline in Daytime Experiences of Shortness of BreathBaseline and 12 weeks

Change from baseline in daytime experiences of shortness of breath based on the weekly mean at week 12.

Daytime experiences of shortness of breath was assessed by the question "how much shortness of breath did you experience during the day" from the e-diary. Scores range from 1 (none) to 5 (a very great deal).

Measured values presented are actually adjusted means.

Change From Baseline in Daytime Experiences of Wheeze or CoughBaseline and 12 weeks

Change from baseline in daytime experiences of wheeze or cough based on the weekly mean at week 12.

Daytime experiences of wheeze or cough was assessed by the question "did you experience wheeze or cough during the day?" from the e-diary. Scores range from 1 (not at all) to 5 (all the time).

Measured values presented are actually adjusted means.

Change From Baseline in Asthma Symptom-free DaysBaseline and 12 weeks

Change from baseline in asthma symptom-free days based on the weekly mean at week 12.

A day was considered as an asthma symptom-free day if there were no symptoms reported via the e-Diary and no use of rescue medication reported via the eDiary during that day.

Measured values presented are actually adjusted means.

Trial Locations

Locations (94)

205.446.01009 Boehringer Ingelheim Investigational Site

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Columbia, Missouri, United States

205.446.01012 Boehringer Ingelheim Investigational Site

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Arlington, Texas, United States

205.446.02001 Boehringer Ingelheim Investigational Site

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Sherbrooke, Quebec, Canada

205.446.48002 Boehringer Ingelheim Investigational Site

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Lodz, Poland

205.446.38002 Boehringer Ingelheim Investigational Site

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Dnipropetrovsk, Ukraine

205.446.38014 Boehringer Ingelheim Investigational Site

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Odesa, Ukraine

205.446.38011 Boehringer Ingelheim Investigational Site

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Zaporizhya, Ukraine

205.446.38005 Boehringer Ingelheim Investigational Site

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Donetsk, Ukraine

205.446.38008 Boehringer Ingelheim Investigational Site

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Zaporizhzhya, Ukraine

205.446.01010 Boehringer Ingelheim Investigational Site

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Oklahoma City, Oklahoma, United States

205.446.01011 Boehringer Ingelheim Investigational Site

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Denver, Colorado, United States

205.446.42002 Boehringer Ingelheim Investigational Site

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Prague, Czech Republic

205.446.49007 Boehringer Ingelheim Investigational Site

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Dresden, Germany

205.446.36004 Boehringer Ingelheim Investigational Site

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Szeged, Hungary

205.446.38013 Boehringer Ingelheim Investigational Site

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Chernivtsi, Ukraine

205.446.38004 Boehringer Ingelheim Investigational Site

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Kiev, Ukraine

205.446.38001 Boehringer Ingelheim Investigational Site

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Lviv, Ukraine

205.446.38003 Boehringer Ingelheim Investigational Site

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Dnipropetrovsk, Ukraine

205.446.70007 Boehringer Ingelheim Investigational Site

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Moscow, Russian Federation

205.446.70003 Boehringer Ingelheim Investigational Site

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St. Petersburg, Russian Federation

205.446.42101 Boehringer Ingelheim Investigational Site

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Kosice, Slovakia

205.446.38006 Boehringer Ingelheim Investigational Site

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Kriviy Rig, Ukraine

205.446.50204 Boehringer Ingelheim Investigational Site

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Guatemala, Guatemala

205.446.37104 Boehringer Ingelheim Investigational Site

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Balvi, Latvia

205.446.37108 Boehringer Ingelheim Investigational Site

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Daugavpils, Latvia

205.446.37003 Boehringer Ingelheim Investigational Site

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Taurage, Lithuania

205.446.42103 Boehringer Ingelheim Investigational Site

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Presov, Slovakia

205.446.70001 Boehringer Ingelheim Investigational Site

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St. Petersburg, Russian Federation

205.446.54007 Boehringer Ingelheim Investigational Site

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San Miguel de Tucuman, Argentina

205.446.01014 Boehringer Ingelheim Investigational Site

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Rolling Hills Estates, California, United States

205.446.01005 Boehringer Ingelheim Investigational Site

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Cincinnati, Ohio, United States

205.446.01003 Boehringer Ingelheim Investigational Site

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North Dartmouth, Massachusetts, United States

205.446.01002 Boehringer Ingelheim Investigational Site

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North Charleston, South Carolina, United States

205.446.01004 Boehringer Ingelheim Investigational Site

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Charleston, South Carolina, United States

205.446.01013 Boehringer Ingelheim Investigational Site

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San Antonio, Texas, United States

205.446.54003 Boehringer Ingelheim Investigational Site

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Capital Federal, Argentina

205.446.54006 Boehringer Ingelheim Investigational Site

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Buenos Aires, Argentina

205.446.54002 Boehringer Ingelheim Investigational Site

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Capital Federal, Argentina

205.446.54008 Boehringer Ingelheim Investigational Site

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Capital Federal, Argentina

205.446.54005 Boehringer Ingelheim Investigational Site

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Mar del Plata, Argentina

205.446.54004 Boehringer Ingelheim Investigational Site

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Mendoza, Argentina

205.446.61001 Boehringer Ingelheim Investigational Site

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Perth, Western Australia, Australia

205.446.32004 Boehringer Ingelheim Investigational Site

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Antwerpen, Belgium

205.446.61003 Boehringer Ingelheim Investigational Site

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Herston, Queensland, Australia

205.446.32005 Boehringer Ingelheim Investigational Site

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Brugge, Belgium

205.446.32006 Boehringer Ingelheim Investigational Site

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Namur, Belgium

205.446.55001 Boehringer Ingelheim Investigational Site

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Curitiba, Brazil

205.446.55007 Boehringer Ingelheim Investigational Site

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Goiânia, Brazil

205.446.55002 Boehringer Ingelheim Investigational Site

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Sao Paulo, Brazil

205.446.55003 Boehringer Ingelheim Investigational Site

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Sao Paulo, Brazil

205.446.55006 Boehringer Ingelheim Investigational Site

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Porto Alegre, Brazil

205.446.02003 Boehringer Ingelheim Investigational Site

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London, Ontario, Canada

205.446.55004 Boehringer Ingelheim Investigational Site

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Sao Paulo, Brazil

205.446.55005 Boehringer Ingelheim Investigational Site

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Sao Paulo, Brazil

205.446.42005 Boehringer Ingelheim Investigational Site

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Jablonec nad Nisou, Czech Republic

205.446.42004 Boehringer Ingelheim Investigational Site

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Prague, Czech Republic

205.446.49012 Boehringer Ingelheim Investigational Site

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Berlin, Germany

205.446.42001 Boehringer Ingelheim Investigational Site

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Jihlava, Czech Republic

205.446.49015 Boehringer Ingelheim Investigational Site

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Berlin, Germany

205.446.49009 Boehringer Ingelheim Investigational Site

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Koblenz, Germany

205.446.49003 Boehringer Ingelheim Investigational Site

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Frankfurt, Germany

205.446.49014 Boehringer Ingelheim Investigational Site

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Marburg, Germany

205.446.49001 Boehringer Ingelheim Investigational Site

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Bochum, Germany

205.446.49011 Boehringer Ingelheim Investigational Site

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Mönchengladbach, Germany

205.446.50201 Boehringer Ingelheim Investigational Site

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Guatemala, Guatemala

205.446.36002 Boehringer Ingelheim Investigational Site

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Ajka, Hungary

205.446.36001 Boehringer Ingelheim Investigational Site

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Budapest, Hungary

205.446.36003 Boehringer Ingelheim Investigational Site

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Nagyatad, Hungary

205.446.37105 Boehringer Ingelheim Investigational Site

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Baldone, Latvia

205.446.37101 Boehringer Ingelheim Investigational Site

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Ogre, Latvia

205.446.37103 Boehringer Ingelheim Investigational Site

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Riga, Latvia

205.446.37004 Boehringer Ingelheim Investigational Site

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Siauliai, Lithuania

205.446.37002 Boehringer Ingelheim Investigational Site

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Utena, Lithuania

205.446.48004 Boehringer Ingelheim Investigational Site

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Bialystok, Poland

205.446.48001 Boehringer Ingelheim Investigational Site

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Lublin, Poland

205.446.70012 Boehringer Ingelheim Investigational Site

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Novosibirsk, Russian Federation

205.446.70002 Boehringer Ingelheim Investigational Site

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Moscow, Russian Federation

205.446.70005 Boehringer Ingelheim Investigational Site

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Moscow, Russian Federation

205.446.70011 Boehringer Ingelheim Investigational Site

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Moscow, Russian Federation

205.446.70004 Boehringer Ingelheim Investigational Site

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St. Petersburg, Russian Federation

205.446.70010 Boehringer Ingelheim Investigational Site

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St. Petersburg, Russian Federation

205.446.70009 Boehringer Ingelheim Investigational Site

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Yaroslavl, Russian Federation

205.446.38012 Boehringer Ingelheim Investigational Site

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Donetsk, Ukraine

205.446.50202 Boehringer Ingelheim Investigational Site

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Guatemala, Guatemala

205.446.37107 Boehringer Ingelheim Investigational Site

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Jekabpils, Latvia

205.446.37106 Boehringer Ingelheim Investigational Site

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Rezekne, Latvia

205.446.37001 Boehringer Ingelheim Investigational Site

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Vilnius, Lithuania

205.446.50203 Boehringer Ingelheim Investigational Site

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Guatemala, Guatemala

205.446.37102 Boehringer Ingelheim Investigational Site

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Riga, Latvia

205.446.40002 Boehringer Ingelheim Investigational Site

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Bucharest, Romania

205.446.42102 Boehringer Ingelheim Investigational Site

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Spisska Nova Ves, Slovakia

205.446.48003 Boehringer Ingelheim Investigational Site

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Tarnow, Poland

205.446.38009 Boehringer Ingelheim Investigational Site

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Kharkiv, Ukraine

205.446.38010 Boehringer Ingelheim Investigational Site

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Vinnytsya, Ukraine

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