Clinical trial NCT01120691: Effect of QVA149 Versus NVA237 and Tiotropium on Chronic Obstructive Pulmonary Disorder (COPD) Exacerbations
Official title: A 64-week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Active Controlled Study to Evaluate the Effect of QVA149 (110/50 μg o.d.) vs NVA237 (50 μg o.d.) and Open-label Tiotropium (18 μg o.d.) on COPD Exacerbations in Patients With Severe to Very Severe Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: QVA149
NVA237
COPD
exacerbation
combination bronchodilator
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-05-11
Enrollment: 2224
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to assess the effect of once-daily QVA149 on COPD exacerbations in patients with severe to very severe COPD.


Eligibility criteria: Inclusion Criteria :

1. Male or female adults aged ≥40 years, who had signed an informed consent form prior to initiation of any study-related procedure.
2. Patients with severe to very severe Chronic Obstructive Pulmonary Disease COPD (Stage III or IV) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines 2008.
3. Current or ex-smokers with a smoking history of at least 10 pack years (Ten pack-years were defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years).
4. Patients with a post-bronchodilator Forced Expiratory Volume in one second ( FEV1) \<50% of the predicted normal value, and post-bronchodilator FEV1/ Forced Vital Capacity (FVC) \<0.70 at Visit 2 (day -14). (Post refers to 1 h after sequential inhalation of 84 µg (or equivalent dose) of ipratropium bromide and 400 µg of salbutamol).
5. A documented history of at least 1 COPD exacerbation in the previous 12 months that required treatment with systemic glucocorticosteroids and/or antibiotics.

Exclusion Criteria:

1. Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test).
2. Women of child-bearing potential
3. Patients requiring long term oxygen therapy (\> 15 h a day) on a daily basis for chronic hypoxemia.
4. Patients who had a COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the 6 weeks prior to visit 1 or between visit 1 (Day -21) and Visit 3 (Day 1).
5. Patients who developed a COPD exacerbation during a period between visit 1 and 3 were ineligible but were permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation.
6. Patients who had a respiratory tract infection within 4 weeks prior to visit 1 (Day -21)

   • Patients who developed an upper or lower respiratory tract infection during the screening period (up to visit 3 (Day 1) were not eligible, but were permitted to be re-screened 4 weeks after the resolution of the respiratory tract infection
7. Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active), clinically significant bronchiectasis, sarcoidosis, interstitial lung disorder or pulmonary hypertension.
8. Patients with lung lobectomy, or lung volume reduction or lung transplantation.
9. Patients who, in the judgment of the investigator, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to):

   * Unstable ischemic heart disease, left ventricular failure, history of myocardial infarction, arrhythmia (excluding chronic stable Atrial Fibrillation (AF). Patients with such events not considered clinically significant by the investigator may be considered for inclusion in the study
   * history of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin
   * uncontrolled hypo- or hyperthyroidism, hypokalemia or hyper adrenergic state
   * narrow-angle glaucoma
   * Symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. (Patients with a Transurethral Resection of Prostate (TURP) were excluded from the study. Patients who underwent full re-section of the prostate could be considered for the study, as well as patients who were asymptomatic and stable on pharmacological treatment for the condition).
   * any condition which might have compromised patient safety or compliance, interfered with evaluation, or precluded completion of the study
10. Patients with any history of asthma indicated by (but not limited to) a blood eosinophil count \> 600/mm3 (at visit 2), or onset of symptoms prior to 40 years. Patients without asthma were excluded if their eosinophil count was \>600/mm3 at visit 2.
11. Patients with allergic rhinitis who used H1 antagonists or intranasal corticosteroids intermittently (treatment with a constant dose was permitted).
12. Patients with eczema (atopic), known high immunoglobulin E (IgE) levels or a known positive skin prick test in the last 5 years.
13. Patients with known history and diagnosis of alpha-1 antitrypsin deficiency.
14. Patients who were participating in the active phase of a supervised pulmonary rehabilitation program.
15. Patients with Type I or uncontrolled Type II diabetes.
16. Patients contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs or drugs of a similar class or any component thereof:

    * anticholinergic agents
    * long and short acting beta-2 agonists
    * sympathomimetic amines.
17. Patients with a history of long QT syndrome or whose corrected QT interval (QTc) measured at visit 2 (Day -14) (Fridericia method) was prolonged (\>450 ms for males and females) as confirmed by the central ECG assessor.
18. Patients with a clinically significant abnormality on the screening or baseline ECG who in the judgment of the investigator would be at potential risk if enrolled into the study. (These patients could not be re-screened).
19. Patients who needed treatments for COPD and allied conditions after the start of the study (visit 1)
20. Patients who needed treatments for COPD and allied conditions (e.g. allergic rhinitis) unless they had been stabilized
21. Patients taking other prohibited medications
22. Patients unable to use a dry powder inhaler (e.g. single dose dry powder inhaler (SDDPI), HandiHaler® device, or pressurized Metered Dose Inhaler (MDI) (rescue medication).
23. Patients unable to use an electronic patient diary.
24. Patients who were, in the opinion of the investigator known to be unreliable or non-compliant.
25. Patients who used other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of visit 1 (day -21), whichever was longer.
26. Patients who had live attenuated vaccination within 30 days prior to the screening visit or during the run-in period. Inactivated influenza vaccination, pneumococcal vaccination or any other inactivated vaccine was acceptable provided it was not administered within 48 hours prior to screening and randomization visits.

No additional exclusions were applied by the investigator, in order to ensure that the study population was representative of all eligible patients.

Primary outcomes:
measure: Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in QVA149 and NVA237 Treatment Arms During the Treatment Period.
timeFrame: 64 weeks
Secondary outcomes:
measure: Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in QVA149 and Open-label Tiotropium Treatment Arms During the Treatment Period.
timeFrame: 76 weeks
measure: Time to First Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Between QVA149, NVA237 and Open Label Tiotropium During the Treatment Period
timeFrame: 64 weeks
measure: Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Requiring the Use of Both Systemic Glucocorticosteroids and Antibiotics
timeFrame: 64 weeks
measure: Number of Days With Moderate or Severe Exacerbation That Required Treatment With Systemic Corticosteroids and Antibiotics
timeFrame: 64 weeks
measure: Time to Study Withdrawal or Premature Discontinuation for Any Reason Between QVA149 (110/50 µg q.d.), NVA237 (50 µg q.d.) and Open Label Tiotropium (18 µg q.d.) During the Treatment Period.
timeFrame: 64 weeks
measure: Percentage of Patients With Study Withdrawal or Premature Discontinuation for Any Reason Between QVA149 (110/50 µg q.d.), NVA237 (50 µg q.d.) and Open Label Tiotropium (18 µg q.d.)During the Treatment Period
timeFrame: 64 weeks
measure: Cumulative Rates of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations for Multiple COPD Exacerbation at Different Time Points
timeFrame: 26, 52, 64, 76 weeks
measure: Pre-dose Forced Expiratory Volume in 1 Second (FEV-1) After 4, 12, 26, 38, 52 and 64 Weeks of Treatment Between QVA149, NVA237 and Open Label Tiotropium
timeFrame: 4, 12, 26, 38, 52 and 64 weeks
measure: Pre-dose Forced Vital Capacity (FVC)After 4, 12, 26, 38, 52 and 64 Weeks of Treatment Between QVA149, NVA237 and Open Label Tiotropium
timeFrame: 4, 12, 26, 38, 52 and 64 weeks
measure: Change in Mean Daily Use (Number of Puffs) of Rescue Therapy Between QVA149, NVA237 and Open Label Tiotropium From Baseling Over the 64 Week Treatment Period
timeFrame: Baseline (14 day run-in), 64 weeks
measure: Change From Baseline of Percentage of Days Without Rescue Therapy Use Between QVA149,NVA237 and Open Label Tiotropium Over the 64 Week Treatment Period
timeFrame: Baseline (14 day run-in), 64 weeks
measure: St. George's Respiratory Questionnaire (SGRQ) Scores Between QVA149, NVA237 and Open Label Tiotropium Over 12, 26, 38, 52 and 64 Weeks of Treatment
timeFrame: 12, 26, 38, 52 and 64 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Fairhope
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Florence
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Homewood
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Jasper
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Pine Bluff
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: Fullerton
country: United States
facility: Novartis Investigative Site
state: California
city: Palo Alto
country: United States
facility: Novartis Investigative Site
state: California
city: Riverside
country: United States
facility: Novartis Investigative Site
state: California
city: San Diego
country: United States
facility: Novartis Investigative Site
state: California
city: San Diego
country: United States
facility: Novartis Investigative Site
state: California
city: San Diego
country: United States
facility: Novartis Investigative Site
state: California
city: Stockton
country: United States
facility: Novartis Investigative Site
state: California
city: Gainesville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Pensacola
country: United States
facility: Novartis Investigative Site
state: Florida
city: Couer D'Alene
country: United States
facility: Novartis Investigative Site
state: Idaho
city: Normal
country: United States
facility: Novartis Investigative Site
state: Illinois
city: River Forest
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Florence
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Louisville
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Opelousas
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Bangor
country: United States
facility: Novartis Investigative Site
state: Maine
city: Fridley
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Ozark
country: United States
facility: Novartis Investigative Site
state: Missouri
city: St. Charles
country: United States
facility: Novartis Investigative Site
state: Missouri
city: St. Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Missoula
country: United States
facility: Novartis Investigative Site
state: Montana
city: Papillion
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Henderson
country: United States
facility: Novartis Investigative Site
state: Nevada
city: Las Vegas
country: United States
facility: Novartis Investigative Site
state: Nevada
city: Reno
country: United States
facility: Novartis Investigative Site
state: Nevada
city: Great Neck
country: United States
facility: Novartis Investigative Site
state: New York
city: Massapequa
country: United States
facility: Novartis Investigative Site
state: New York
city: Charlotte
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Raleigh
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Wilmington
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Medford
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Beaver
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Erie
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Charleston
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Spartanburg
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Fort Worth
country: United States
facility: Novartis Investigative Site
state: Texas
city: Ft. Worth
country: United States
facility: Novartis Investigative Site
state: Texas
city: Salt Lake City
country: United States
facility: Novartis Investigative Site
state: Utah
city: Salem
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Tacoma
country: United States
facility: Novartis Investigative Site
state: Washington
city: Green Bay
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Capital Federal
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: La Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: San Isidro
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Novartis Investigative Site
state: Tucuman
city: San Miguel de Tucuman
country: Argentina
facility: Novartis Investigative Site
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Corrientes
country: Argentina
facility: Novartis Investigative Site
city: Mendoza
country: Argentina
facility: Novartis Investigative Site
city: Mendoza
country: Argentina
facility: Novartis Investigative Site
city: Paraná Entre Ríos
country: Argentina
facility: Novartis Investigative Site
city: Santa Fe
country: Argentina
facility: Novartis Investigative Site
city: Feldbach
country: Austria
facility: Novartis Investigative Site
city: Grieskirchen
country: Austria
facility: Novartis Investigative Site
city: Linz
country: Austria
facility: Novartis Investigative Site
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Thalheim bei Wels
country: Austria
facility: Novartis Investigative Site
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Mississauga
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Joliette
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Laval
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Québec
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: St-Romuald
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Trois-Rivières
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Bogota
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Armenia
country: Colombia
facility: Novartis Investigative Site
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
city: Bogotá
country: Colombia
facility: Novartis Investigative Site
city: Medellin
country: Colombia
facility: Novartis Investigative Site
city: Medellín
country: Colombia
facility: Novartis Investigative Site
city: Cesky Krumlov
country: Czech Republic
facility: Novartis Investigative Site
city: Cvikov
country: Czech Republic
facility: Novartis Investigative Site
city: Havlickuv Brod
country: Czech Republic
facility: Novartis Investigative Site
city: Jaromer
country: Czech Republic
facility: Novartis Investigative Site
city: Karlovy Vary
country: Czech Republic
facility: Novartis Investigative Site
city: Kromeriz
country: Czech Republic
facility: Novartis Investigative Site
city: Kutna Hora
country: Czech Republic
facility: Novartis Investigative Site
city: Kyjov
country: Czech Republic
facility: Novartis Investigative Site
city: Liberec
country: Czech Republic
facility: Novartis Investigative Site
city: Pardubice
country: Czech Republic
facility: Novartis Investigative Site
city: Prague 4
country: Czech Republic
facility: Novartis Investigative Site
city: Praha 10
country: Czech Republic
facility: Novartis Investigative Site
city: Praha 9
country: Czech Republic
facility: Novartis Investigative Site
city: Rokycany
country: Czech Republic
facility: Novartis Investigative Site
city: Strakonice
country: Czech Republic
facility: Novartis Investigative Site
city: Teplice
country: Czech Republic
facility: Novartis Investigative Site
city: Zatec
country: Czech Republic
facility: Novartis Investigative Site
city: Znojmo
country: Czech Republic
facility: Novartis Investigative Site
city: Aalborg
country: Denmark
facility: Novartis Investigative Site
city: Copenhagen NV
country: Denmark
facility: Novartis Investigative Site
city: Hellerup
country: Denmark
facility: Novartis Investigative Site
city: Hvidovre
country: Denmark
facility: Novartis Investigative Site
city: Roskilde
country: Denmark
facility: Novartis Investigative Site
city: Silkeborg
country: Denmark
facility: Novartis Investigative Site
city: Sønderborg
country: Denmark
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Jyvaskyla
country: Finland
facility: Novartis Investigative Site
city: Turku
country: Finland
facility: Novartis Investigative Site
city: Bayonne Cedex
country: France
facility: Novartis Investigative Site
city: Beuvry
country: France
facility: Novartis Investigative Site
city: Ferolles-Attily
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Koblenz
country: Germany
facility: Novartis Investigative Site
state: NRW
city: Aschaffenburg
country: Germany
facility: Novartis Investigative Site
city: Bamberg
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Dueren
country: Germany
facility: Novartis Investigative Site
city: Duisburg
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Freudenberg
country: Germany
facility: Novartis Investigative Site
city: Fulda
country: Germany
facility: Novartis Investigative Site
city: Gelsenkirchen
country: Germany
facility: Novartis Investigative Site
city: Gummersbach
country: Germany
facility: Novartis Investigative Site
city: Hagen
country: Germany
facility: Novartis Investigative Site
city: Halle
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Homburg
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Langenfeld
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Lübeck
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Nuernberg
country: Germany
facility: Novartis Investigative Site
city: Oranienburg
country: Germany
facility: Novartis Investigative Site
city: Potsdam
country: Germany
facility: Novartis Investigative Site
city: Radebeul
country: Germany
facility: Novartis Investigative Site
city: Reinfeld
country: Germany
facility: Novartis Investigative Site
city: Saarbruecken
country: Germany
facility: Novartis Investigative Site
city: Schwerte
country: Germany
facility: Novartis Investigative Site
city: Schwetzingen
country: Germany
facility: Novartis Investigative Site
city: Solingen
country: Germany
facility: Novartis Investigative Site
city: Stade
country: Germany
facility: Novartis Investigative Site
city: Teterow
country: Germany
facility: Novartis Investigative Site
city: Wissen
country: Germany
facility: Novartis Investigative Site
city: Athens - GR
country: Greece
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Larissa
country: Greece
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: Baja
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Cegled
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Deszk
country: Hungary
facility: Novartis Investigative Site
city: Eger
country: Hungary
facility: Novartis Investigative Site
city: Makó
country: Hungary
facility: Novartis Investigative Site
city: Mosonmagyarovar
country: Hungary
facility: Novartis Investigative Site
city: Sopron
country: Hungary
facility: Novartis Investigative Site
city: Szarvas
country: Hungary
facility: Novartis Investigative Site
city: Szekszard
country: Hungary
facility: Novartis Investigative Site
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: A.p.
city: Hyderbabd
country: India
facility: Novartis Investigative Site
state: Andhra Pradesh
city: New Delhi
country: India
facility: Novartis Investigative Site
state: Delhi
city: Mysore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Nashik
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Pune
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Jaipur
country: India
facility: Novartis Investigative Site
state: Rajasthan
city: Coimbatore
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Coimbatore
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Coimbatore
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Nagpur - Maharastra
country: India
facility: Novartis Investigative Site
city: Panjim
country: India
facility: Novartis Investigative Site
city: Secunderabad
country: India
facility: Novartis Investigative Site
city: Trivandrum
country: India
facility: Novartis Investigative Site
city: Dublin 15
country: Ireland
facility: Novartis Investigative Site
city: Dublin 24
country: Ireland
facility: Novartis Investigative Site
city: Dublin 4
country: Ireland
facility: Novartis Investigative Site
city: Dublin 9
country: Ireland
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Ashkelon
country: Israel
facility: Novartis Investigative Site
city: Beer-Sheva
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Kfar-Sava
country: Israel
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Rehovot
country: Israel
facility: Novartis Investigative Site
city: Tel-Aviv
country: Israel
facility: Novartis Investigative Site
city: Osimo
country: Italy
facility: Novartis Investigative Site
state: AN
city: Catania
country: Italy
facility: Novartis Investigative Site
state: CT
city: Foggia
country: Italy
facility: Novartis Investigative Site
state: FG
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Arenzano
country: Italy
facility: Novartis Investigative Site
state: GE
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Abano Terme
country: Italy
facility: Novartis Investigative Site
state: PD
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Riccione
country: Italy
facility: Novartis Investigative Site
state: RN
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Pietra Ligure
country: Italy
facility: Novartis Investigative Site
state: SV
city: Montecchio Maggiore
country: Italy
facility: Novartis Investigative Site
state: VI
city: Pisa
country: Italy
facility: Novartis Investigative Site
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Zapopan
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
state: Nuevo León
city: San Luis Potosí
country: Mexico
facility: Novartis Investigative Site
city: Almelo
country: Netherlands
facility: Novartis Investigative Site
city: Breda
country: Netherlands
facility: Novartis Investigative Site
city: Dordrecht
country: Netherlands
facility: Novartis Investigative Site
city: Drachten
country: Netherlands
facility: Novartis Investigative Site
city: Enschede
country: Netherlands
facility: Novartis Investigative Site
city: Harderwijk
country: Netherlands
facility: Novartis Investigative Site
city: Helmond
country: Netherlands
facility: Novartis Investigative Site
city: Hoofddorp
country: Netherlands
facility: Novartis Investigative Site
city: Hoorn
country: Netherlands
facility: Novartis Investigative Site
city: Leeuwarden
country: Netherlands
facility: Novartis Investigative Site
city: Roermond
country: Netherlands
facility: Novartis Investigative Site
city: Veldhoven
country: Netherlands
facility: Novartis Investigative Site
city: Voorburg
country: Netherlands
facility: Novartis Investigative Site
city: Cercado de Lima
country: Peru
facility: Novartis Investigative Site
state: Lima
city: San Borja
country: Peru
facility: Novartis Investigative Site
state: Lima
city: San Isidro
country: Peru
facility: Novartis Investigative Site
state: Lima
city: San Martin de Porres
country: Peru
facility: Novartis Investigative Site
state: Lima
city: San Miguel
country: Peru
facility: Novartis Investigative Site
state: Lima
city: Santiago de Surco
country: Peru
facility: Novartis Investigative Site
state: Lima
city: Quezon City
country: Philippines
facility: Novartis Investigative Site
state: Metro Manila
city: Bulacan
country: Philippines
facility: Novartis Investigative Site
city: Las Pinas
country: Philippines
facility: Novartis Investigative Site
city: Manila
country: Philippines
facility: Novartis Investigative Site
city: Quezon City
country: Philippines
facility: Novartis Investigative Site
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Katowice
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Mrozy
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Humacao
country: Puerto Rico
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
state: Tatarstan Republic
city: Barnaul
country: Russian Federation
facility: Novartis Investigative Site
city: Chelyabinsk
country: Russian Federation
facility: Novartis Investigative Site
city: Ekaterinburg
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Rostov-on-Don
country: Russian Federation
facility: Novartis Investigative Site
city: Ryazan
country: Russian Federation
facility: Novartis Investigative Site
city: S.-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Samara
country: Russian Federation
facility: Novartis Investigative Site
city: Sankt-Peterburg
country: Russian Federation
facility: Novartis Investigative Site
city: St-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St.Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Yaroslavl
country: Russian Federation
facility: Novartis Investigative Site
city: Banska Bystrica
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Bojnice
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Humenne
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Partizanske
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Kosice
country: Slovakia
facility: Novartis Investigative Site
city: Kralovsky Chlmec
country: Slovakia
facility: Novartis Investigative Site
city: Martin
country: Slovakia
facility: Novartis Investigative Site
city: Presov
country: Slovakia
facility: Novartis Investigative Site
city: Trnava
country: Slovakia
facility: Novartis Investigative Site
city: Durban
country: South Africa
facility: Novartis Investigative Site
city: Newtown, Johannesburg
country: South Africa
facility: Novartis Investigative Site
city: Pretoria
country: South Africa
facility: Novartis Investigative Site
city: Pretoria
country: South Africa
facility: Novartis Investigative Site
city: Pretoria
country: South Africa
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: L'Hospitalet de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Alicante
country: Spain
facility: Novartis Investigative Site
city: Stockton
country: United Kingdom
facility: Novartis Investigative Site
state: Cleveland
city: Sneinton
country: United Kingdom
facility: Novartis Investigative Site
state: Nottingham
city: Taunton
country: United Kingdom
facility: Novartis Investigative Site
state: Somerset
city: Chertsey
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
city: Blackpool
country: United Kingdom
facility: Novartis Investigative Site
city: Bradford
country: United Kingdom
facility: Novartis Investigative Site
city: Bristol
country: United Kingdom
facility: Novartis Investigative Site
city: Coventry
country: United Kingdom
facility: Novartis Investigative Site
city: Gillingham
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: Hereford
country: United Kingdom
facility: Novartis Investigative Site
city: Huntingdon
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Merseyside
country: United Kingdom
facility: Novartis Investigative Site
city: Portsmouth
country: United Kingdom
facility: Novartis Investigative Site
city: Telford
country: United Kingdom
facility: Novartis Investigative Site
city: Wolverhampton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Wedzicha JA, Decramer M, Ficker JH, Niewoehner DE, Sandstrom T, Taylor AF, D'Andrea P, Arrasate C, Chen H, Banerji D. Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, double-blind, parallel-group study. Lancet Respir Med. 2013 May;1(3):199-209. doi: 10.1016/S2213-2600(13)70052-3. Epub 2013 Apr 23.