A Multicenter Randomized 52 Week Treatment Double-blind, Triple Dummy Parallel Group Study to Assess the Efficacy and Safety of QMF149 Compared to Mometasone Furoate in Participants With Asthma

NCT ID: NCT02554786

Last Updated: 2020-03-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2216 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-29

Study Completion Date

2019-06-28

Brief Summary

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The purpose of the trial is to evaluate the efficacy and safety of two different doses of QMF149 (QMF149 150/160 µg and QMF149 150/320 µg via Concept1) over two respective MF doses (MF 400 µg and MF 800 µg via Twisthaler® (total daily dose)) in poorly controlled asthmatic participants as determined by pulmonary function testing, and effects on asthma control

Detailed Description

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Conditions

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Asthma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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QMF149 150/160 µg

QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered once daily (o.d) via Concept1 inhaler in the evening.

Group Type EXPERIMENTAL

Indacaterol acetate/Mometasone furoate

Intervention Type DRUG

QMF149 150/320 µg

QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d via Concept1 inhaler in the evening.

Group Type EXPERIMENTAL

Indacaterol acetate/Mometasone furoate

Intervention Type DRUG

MF 400 µg

Mometasone furoate (MF) 400 μg was delivered o.d via Twisthaler® in the evening

Group Type ACTIVE_COMPARATOR

Mometasone furoate

Intervention Type DRUG

Salmeterol /fluticasone 50/500 μg

Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®.

Group Type ACTIVE_COMPARATOR

Salmeterol xinafoate/fluticasone propionate

Intervention Type DRUG

MF 800 μg

MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®.

Group Type ACTIVE_COMPARATOR

Mometasone furoate

Intervention Type DRUG

Interventions

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Indacaterol acetate/Mometasone furoate

Intervention Type DRUG

Mometasone furoate

Intervention Type DRUG

Salmeterol xinafoate/fluticasone propionate

Intervention Type DRUG

Other Intervention Names

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QMF149

Eligibility Criteria

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Inclusion Criteria

* Participants with a diagnosis of asthma, for a period of at least 1 year prior to Visit 1 (Screening)
* Participants who have used medium or high dose inhaled corticosteroids (ICS) or low dose of long acting beta-2 agonist (LABA)/ICS combinations for asthma for at least 3 months and at stable doses for at least 1 month prior to Visit 1
* Participants must have ACQ-7 score ≥ 1.5 at Visit 101 and at Visit 102 (prior to double-blind treatment) and qualify for treatment with medium or high dose LABA/ICS
* Pre-bronchodilator ≥ 50% Forced expiratory volume in 1 second (FEV1) of \< 85 % of the predicted normal value for the participants after withholding bronchodilators at both Visit 101 and 102, according to American Thoracic Society/European Respiratory Society (ATS/ERS) criteria.
* Withholding period of bronchodilators prior to spirometry: short acting beta-2 agonist (SABA) for ≥ 6 hours and FDC or free combinations of ICS/LABA for ≥ 48 hours, short acting anticholinergics (SAMA) for ≥ 8 hours, xanthines \>=07 days
* A one-time repeat/re-testing of percent predicted FEV1 (prebronchodilator FEV1) is allowed at Visit 101 and at Visit 102.

Spacer devices are permitted for reversibility testing only.

-Participants who demonstrate an increase in FEV1 of 12% and 200 mL within 30 minutes after administration of 400 µg salbutamol/360 µg albuterol (or equivalent dose) at Visit 101 All participants must perform a reversibility test at Visit 101

If reversibility is not demonstrated at Visit 101:

* Reversibility should be repeated once-
* Participants may be permitted to enter the study with historical evidence of reversibility that was performed according to ATS/ERS guidelines within 2 years prior to Visit 1
* Alternatively, participants may be permitted to enter the study with a historical positive bronchoprovocation test that was performed within 2 years prior to Visit 1.

Exclusion Criteria

* Participants who have smoked or inhaled tobacco products within the 6 month period prior to Visit 1, or who have a smoking history of greater than 10 pack years. This includes use of nicotine inhalers such as e-cigarettes at the time of Visit 1
* Participants who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening)
* Participants who have ever required intubation for a severe asthma attack/exacerbation.
* Participants who have a clinical condition which is likely to be worsened by ICS administration (e.g. glaucoma, cataract and fragility fractures) who are according to investigator's medical judgment at risk participating in the study).
* Participants who have had a respiratory tract infection or asthma worsening as determined by the investigator within 4 weeks prior to Visit 1 (Screening) or between Visit 1 and Visit 102. Participants may be re-screened 4 weeks after recovery from their respiratory tract infection or asthma worsening.
* Participants with a history of chronic lung diseases other than asthma, including (but not limited to) Chronic Obstructive Pulmonary Disease (COPD), sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis.
* Participants with severe narcolepsy and/or insomnia.
* Participants who have a clinically significant electrocardiogram (ECG) abnormality at Visit 101 (Start of Run- In epoch) and at any time between Visit 101 and Visit 102 (including unscheduled ECG). ECG evidence of myocardial infarction at Visit 101 (via central reader) should be clinically assessed by the investigator with supportivedocumentation
* Participants with a history of hypersensitivity to lactose, any of the study drugs or to similar drugs within the class including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof
* Participants who have not achieved an acceptable spirometry results at Visit 101 in accordance with ATS/ERS criteria for acceptability and repeatability (rescreening allowed only once).

Repeat spirometry may be allowed once in an ad-hoc visit if the spirometry did not qualify due to ATS/ERS criteria. If the participant fails the repeat assessment, the participant may be rescreened once

* Participants on Maintenance Immunotherapy (desensitization) for allergies or less than 3 months prior to Visit 101 or participants on Maintenance Immunotherapy for more than 3 months prior to Visit 101 but expected to change throughout the course of the study.
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment and for 30 days after stopping of study treatment.
* Long acting muscarinic antagonist (LAMA) use within 3 months prior to Visit 101
Minimum Eligible Age

12 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Novartis Investigative Site

Birmingham, Alabama, United States

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Los Angeles, California, United States

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Orange, California, United States

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Riverside, California, United States

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San Diego, California, United States

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San Jose, California, United States

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Stockton, California, United States

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Westminster, California, United States

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Denver, Colorado, United States

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Miami, Florida, United States

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Tallahassee, Florida, United States

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Winter Park, Florida, United States

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Baltimore, Maryland, United States

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Waldorf, Maryland, United States

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North Dartmouth, Massachusetts, United States

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St Louis, Missouri, United States

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Bellevue, Nebraska, United States

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Las Vegas, Nevada, United States

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Skillman, New Jersey, United States

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Cortland, New York, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Medford, Oregon, United States

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Portland, Oregon, United States

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Pittsburgh, Pennsylvania, United States

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North Charleston, South Carolina, United States

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Boerne, Texas, United States

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El Paso, Texas, United States

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Greenfield, Wisconsin, United States

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Plovdiv, BGR, Bulgaria

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Varna, BGR, Bulgaria

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Vidin, BGR, Bulgaria

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Pleven, , Bulgaria

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Plovdiv, , Bulgaria

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Rousse, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Stara Zagora, , Bulgaria

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Troyan Municipality, , Bulgaria

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Beijing, Beijing Municipality, China

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Beijing, Beijing Municipality, China

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Fuzhou, Fujian, China

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Guangzhou, Guangdong, China

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Haikou, Hainan, China

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Shijiazhuang, Hebei, China

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Wuhan, Hubei, China

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Changsha, Hunan, China

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Nanjing, Jiangsu, China

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Suzhou, Jiangsu, China

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Changchun, Jilin, China

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Shenyang, Liaoning, China

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Shenyang, Liaoning, China

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Shanghai, Shanghai Municipality, China

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Xian, Shanxi, China

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Chengdu, Sichuan, China

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Hangzhou, Zhejiang, China

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Beijing, , China

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Nanchang, , China

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Tianjin, , China

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Varaždin, HRV, Croatia

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Zagreb, HRV, Croatia

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Petrinja, , Croatia

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Rijeka, , Croatia

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Zadar, , Croatia

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Zagreb, , Croatia

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Beroun, Czech Republic, Czechia

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Boskovice, Czech Republic, Czechia

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Jablonec nad Nisou, Czech Republic, Czechia

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Jindřichův Hradec, Czech Republic, Czechia

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Kuřim, Czech Republic, Czechia

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Prague, Czech Republic, Czechia

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Varnsdorf, Czech Republic, Czechia

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Ostrava, CZE, Czechia

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Prague, , Czechia

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Alexandria, , Egypt

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Tallinn, , Estonia

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Tartu, , Estonia

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Peine, Lower Saxony, Germany

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Koblenz, Rhineland-Palatinate, Germany

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Ahlen, , Germany

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Bonn, , Germany

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Delitzsch, , Germany

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Erlangen, , Germany

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Frankfurt, , Germany

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Frankfurt, , Germany

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Fürstenwalde, , Germany

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Halle, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Hochstadt, , Germany

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Kassel, , Germany

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Leipzig, , Germany

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Leipzig, , Germany

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Leipzig, , Germany

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Leipzig, , Germany

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Ludwigsburg, , Germany

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Lübeck, , Germany

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Marburg, , Germany

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Mittweida, , Germany

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München, , Germany

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Neu-Isenburg, , Germany

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Neuss, , Germany

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Potsdam, , Germany

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Potsdam, , Germany

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Rheine, , Germany

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Rudersdorf, , Germany

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Schleswig, , Germany

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Schwedt, , Germany

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Weinheim, , Germany

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Witten, , Germany

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Ciudad, Gautemala, Guatemala

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Guatemala City, GTM, Guatemala

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Guatemala City, GTM, Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Budapest, HUN, Hungary

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Budapest, HUN, Hungary

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Budapest, HUN, Hungary

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Budapest, HUN, Hungary

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Győr, HUN, Hungary

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Hajdúnánás, HUN, Hungary

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Makó, HUN, Hungary

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Miskolc, HUN, Hungary

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Püspökladány, HUN, Hungary

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Százhalombatta, HUN, Hungary

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Balassagyarmat, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Cegléd, , Hungary

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Csorna, , Hungary

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Dombóvár, , Hungary

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Gödöllő, , Hungary

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Hatvan, , Hungary

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Komárom, , Hungary

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Miskolc, , Hungary

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Mosdós, , Hungary

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Szarvas, , Hungary

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Szeged, , Hungary

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Szeged, , Hungary

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Szigetvár, , Hungary

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Szombathely, , Hungary

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Ahmedabad, Gujarat, India

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Ahmedabad, Gujarat, India

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Vadodara, Gujarat, India

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Mysore, Karnataka, India

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Kozhikode, Kerala, India

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Mumbai, Maharashtra, India

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Nagpur, Maharashtra, India

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Nagpur, Maharashtra, India

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Nagpur, Maharashtra, India

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Pune, Maharashtra, India

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New Delhi, National Capital Territory of Delhi, India

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Mohali, Punjab, India

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Jaipur, Rajasthan, India

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Jaipur, Rajasthan, India

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Jaipur, Rajasthan, India

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Jaipur, Rajasthan, India

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Hyderabad, Telangana, India

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Lucknow, Uttar Pradesh, India

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New Delhi, , India

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Wilton, Cork, Ireland

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County Limerick, , Ireland

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Dublin, , Ireland

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Ichihara, Chiba, Japan

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Fukuoka, Fukuoka, Japan

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Kasuga, Fukuoka, Japan

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Yanagawa, Fukuoka, Japan

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Obihiro, Hokkaido, Japan

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Himeji, Hyōgo, Japan

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Himeji, Hyōgo, Japan

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Naka-gun, Ibaraki, Japan

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Atsugi, Kanagawa, Japan

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Kawasaki, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Sendai, Miyagi, Japan

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Okayama, Okayama-ken, Japan

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Kishiwada, Osaka, Japan

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Osaka, Osaka, Japan

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Takatsuki, Osaka, Japan

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Toyonaka, Osaka, Japan

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Yao, Osaka, Japan

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Koshigaya, Saitama, Japan

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Tokyo, Shibuya Ku, Japan

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Chuo Ku, Tokyo, Japan

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Chuou-ku, Tokyo, Japan

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Itabashi-ku, Tokyo, Japan

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Setagaya-Ku, Tokyo, Japan

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Shinjuku-ku, Tokyo, Japan

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Toshima Ku, Tokyo, Japan

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Riga, LV, Latvia

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Daugavpils, , Latvia

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Riga, , Latvia

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Riga, , Latvia

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Kaunas, LTU, Lithuania

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Kaunas, , Lithuania

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Šiauliai, , Lithuania

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Utena, , Lithuania

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Vilnius, , Lithuania

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Mexicali, Estado de Baja California, Mexico

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Mexico City, Mexico City, Mexico

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Mexico City, Mexico City, Mexico

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México, , Mexico

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Aleksandrow Odzki, Poland, Poland

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Biaystok, Poland, Poland

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Lodz, POL, Poland

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Wejherowo, POL, Poland

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Bielsko-Biala, , Poland

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Elblag, , Poland

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Inowrocław, , Poland

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Katowice, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Ostrów Wielkopolski, , Poland

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Sopot, , Poland

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Warsaw, , Poland

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Zawadzkie, , Poland

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Iași, Jud Iasi, Romania

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Constanța, Jud. Constanta, Romania

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Craiova, Jud.Dolj, Romania

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Bucharest, ROM, Romania

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Craiova, ROM, Romania

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Craiova, ROM, Romania

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Deva, ROM, Romania

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Timișoara, ROM, Romania

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Timișoara, Timiș County, Romania

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Arad, , Romania

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Bacau, , Romania

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Bragadiru, , Romania

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Brasov, , Romania

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Brăila, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Cluj-Napoca, , Romania

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Cluj-Napoca, , Romania

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Codlea, , Romania

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Craiova, , Romania

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Râmnicu Vâlcea, , Romania

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Suceava, , Romania

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Târgu Mureş, , Romania

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Yaroslavl, Russian Federation, Russia

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Chelyabinsk, , Russia

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Chelyabinsk, , Russia

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Kazan', , Russia

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Krasnoyarsk, , Russia

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Moscow, , Russia

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Moscow, , Russia

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N.Novgorod, , Russia

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Novosibirsk, , Russia

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Novosibirsk, , Russia

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Penza, , Russia

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Petrozavodsk, , Russia

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Pyatigorsk, , Russia

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Ryazan, , Russia

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Ryazan, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saratov, , Russia

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Saratov, , Russia

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Smolensk, , Russia

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Smolensk, , Russia

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Stavropol, , Russia

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Volgograd, , Russia

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Vologodonsk, , Russia

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Yaroslavl, , Russia

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Yaroslavl, , Russia

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Yaroslavl, , Russia

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Yekaterinburg, , Russia

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Belgrade, Serbia, Serbia

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Belgrade, , Serbia

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Kamenitz, , Serbia

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Kragujevac, , Serbia

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Niš, , Serbia

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Bardejov, Slovak Republic, Slovakia

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Bojnice, Slovak Republic, Slovakia

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Bratislava, Slovak Republic, Slovakia

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Humenné, Slovak Republic, Slovakia

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Košice, Slovak Republic, Slovakia

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Nitra, Slovak Republic, Slovakia

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Skalica, Slovak Republic, Slovakia

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Spišská Nová Ves, Slovak Republic, Slovakia

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Stropkov, Slovak Republic, Slovakia

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Šurany, Slovak Republic, Slovakia

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Veľký Meder, Slovak Republic, Slovakia

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Námestovo, Slovensko, Slovakia

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Poprad, SVK, Slovakia

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Bardejov, , Slovakia

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Bratislava, , Slovakia

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Čadca, , Slovakia

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Ilava, , Slovakia

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Komárno, , Slovakia

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Košice, , Slovakia

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Košice, , Slovakia

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Kráľovský Chlmec, , Slovakia

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Levice, , Slovakia

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Liptovský Mikuláš, , Slovakia

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Prešov, , Slovakia

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Prievidza, , Slovakia

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Topoľčany, , Slovakia

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Žilina, , Slovakia

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Žilina, , Slovakia

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Berea, Durban, South Africa

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Belleville, South Africa, South Africa

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Panorama, Western Cape, South Africa

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Cape Town, , South Africa

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Cape Town, , South Africa

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Cape Town, , South Africa

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Wŏnju, Gangwon-do, South Korea

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Bucheon-si, Gyeonggi-do, South Korea

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Bundang Gu, Gyeonggi-do, South Korea

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Seoul, Korea, South Korea

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Seoul, Korea, South Korea

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Cheongju-si, North Chungcheong, South Korea

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Seoul, Seocho Gu, South Korea

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Incheon, , South Korea

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Fowey, Cornwall, United Kingdom

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Liskeard, Cornwall, United Kingdom

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Torpoint, Cornwall, United Kingdom

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Faringdon, Oxfordshire, United Kingdom

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Bristol, South Gloucestershire, United Kingdom

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Blackpool, , United Kingdom

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Denbighshire, , United Kingdom

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Glasgow, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Novartis Investigative Site

Rotherham, , United Kingdom

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Novartis Investigative Site

Wiltshire, , United Kingdom

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Countries

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United States Bulgaria China Croatia Czechia Egypt Estonia Germany Guatemala Hungary India Ireland Japan Latvia Lithuania Mexico Poland Romania Russia Serbia Slovakia South Africa South Korea United Kingdom

References

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Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.

Reference Type DERIVED
PMID: 36472162 (View on PubMed)

Chapman K, van Zyl-Smit R, Maspero J, Kerstjens HAM, Gon Y, Hosoe M, Tanase AM, Pethe A, Shu X, D'Andrea P. One time a day mometasone/indacaterol fixed-dose combination versus two times a day fluticasone/salmeterol in patients with inadequately controlled asthma: pooled analysis from PALLADIUM and IRIDIUM studies. BMJ Open Respir Res. 2021 Aug;8(1):e000819. doi: 10.1136/bmjresp-2020-000819.

Reference Type DERIVED
PMID: 34452934 (View on PubMed)

van Zyl-Smit RN, Krull M, Gessner C, Gon Y, Noga O, Richard A, de Los Reyes A, Shu X, Pethe A, Tanase AM, D'Andrea P; PALLADIUM trial investigators. Once-daily mometasone plus indacaterol versus mometasone or twice-daily fluticasone plus salmeterol in patients with inadequately controlled asthma (PALLADIUM): a randomised, double-blind, triple-dummy, controlled phase 3 study. Lancet Respir Med. 2020 Oct;8(10):987-999. doi: 10.1016/S2213-2600(20)30178-8. Epub 2020 Jul 9.

Reference Type DERIVED
PMID: 32653075 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-002529-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CQVM149B2301

Identifier Type: -

Identifier Source: org_study_id

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