Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02164513




Registration number
NCT02164513
Ethics application status
Date submitted
12/06/2014
Date registered
16/06/2014
Date last updated
10/10/2018

Titles & IDs
Public title
A Study Comparing the Efficacy, Safety and Tolerability of Fixed Dose Combination (FDC) of FF/UMEC/VI With the FDC of FF/VI and UMEC/VI; Administered Once-daily Via a Dry Powder Inhaler (DPI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Scientific title
A Phase III, 52 Week, Randomized, Double-blind, 3-arm Parallel Group Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination FF/UMEC/VI With the Fixed Dose Dual Combinations of FF/VI and UMEC/VI, All Administered Once-daily in the Morning Via a Dry Powder Inhaler in Subjects With Chronic Obstructive Pulmonary Disease
Secondary ID [1] 0 0
116855
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Disease, Chronic Obstructive 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - fluticasone furoate (FF)
Treatment: Drugs - vilanterol (VI)
Treatment: Drugs - umeclidinium bromide (UMEC)

Experimental: fluticasone furoate/umeclidinium bromide/vilanterol - Eligible Subjects completing 2-weeks run-in period will receive FF/UMEC/VI 100 mcg/62.5 mcg/25 mcg QD (morning) for a period of 52 weeks via DPI

Experimental: fluticasone furoate/vilanterol - Eligible Subjects completing 2-weeks run-in period will receive FF/VI 100 mcg/25 mcg QD (morning) for a treatment period of 52 weeks via DPI)

Experimental: umeclidinium bromide/vilanterol - Eligible Subjects completing 2-weeks run-in period will receive UMEC/VI 62.5 mcg/25 mcg QD (morning) for a treatment period of 52 weeks via DPI


Treatment: Drugs: fluticasone furoate (FF)
FF will be available in combination as dry powder for inhalation as FF/UMEC/VI 100 mcg/62.5 mcg/25 mcg and FF/VI 100 mcg/25 mcg

Treatment: Drugs: vilanterol (VI)
VI will be available in combination as dry powder for inhalation as FF/UMEC/VI 100 mcg/62.5 mcg/25 mcg, FF/VI 100 mcg/25 mcg and UMEC/VI 62.5 mcg/25 mcg

Treatment: Drugs: umeclidinium bromide (UMEC)
UMEC will be available in combination as dry powder for inhalation as FF/UMEC/VI 100 mcg/62.5 mcg/25 mcg, and UMEC/VI 62.5 mcg/25 mcg
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annual Rate of On-treatment Moderate/Severe Exacerbations Comparing FF/UMEC/VI With UMEC/VI and FF/VI
Timepoint [1] 0 0
Up to Week 52
Secondary outcome [1] 0 0
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1), at Week 52 Comparing FF/UMEC/VI With FF/VI
Timepoint [1] 0 0
Baseline and Week 52
Secondary outcome [2] 0 0
Change From Baseline in St. George's Respiratory Questionnaire for (SGRQ) Total Score at Week 52 Comparing FF/UMEC/VI With FF/VI
Timepoint [2] 0 0
Baseline and Week 52
Secondary outcome [3] 0 0
Time to First On-treatment Moderate/Severe Exacerbation Comparing FF/UMEC/VI With FF/VI and With UMEC/VI
Timepoint [3] 0 0
Up to Week 52
Secondary outcome [4] 0 0
Annual Rate of On-treatment Moderate/Severe Exacerbations Comparing FF/UMEC/VI With UMEC/VI in the Subset of Participants With a Blood Eosinophil Count >=150 Cells Per Microliter
Timepoint [4] 0 0
Up to Week 52
Secondary outcome [5] 0 0
Time to First On-treatment Moderate/Severe Exacerbation Comparing FF/UMEC/VI With UMEC/VI in the Subset of Particpants With a Blood Eosinophil Count >=150 Cells Per Microliter at Baseline
Timepoint [5] 0 0
Up to Week 52
Secondary outcome [6] 0 0
Annual Rate of On-treatment Severe Exacerbations Comparing FF/UMEC/VI With FF/VI and With UMEC/VI
Timepoint [6] 0 0
Up to Week 52

Eligibility
Key inclusion criteria
- Informed Consent: A signed and dated written informed consent prior to study
participation

- Type of subject: Outpatient

- Age: Subjects 40 years of age or older at Visit 1

- Gender: Male or female subjects. A female is eligible to enter and participate in the
study if she is of: Non-child bearing potential (i.e. physiologically incapable of
becoming pregnant, including any female who is post-menopausal or surgically sterile).
Surgically sterile females are defined as those with a documented hysterectomy and/or
bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being
amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g. age
appropriate, > 45 years, in the absence of hormone replacement therapy OR Child
bearing potential, has a negative pregnancy test at screening, and agrees to one of
the following acceptable contraceptive methods used consistently and correctly (i.e.
in accordance with the approved product label and the instructions of the physician
for the duration of the study - screening to safety follow-up contact): Abstinence;
Oral Contraceptive, either combined or progestogen alone; Injectable progestogen;
Implants of levonorgestrel; Estrogenic vaginal ring; Percutaneous contraceptive
patches; Intrauterine device (IUD) or intrauterine system (IUS); Male partner
sterilization (vasectomy with documentation of azoospermia) prior to the female
subject's entry into the study, and this male is the sole partner for that subject.
For this definition, "documented" refers to the outcome of the
investigator's/designee's medical examination of the subject or review of the
subject's medical history for study eligibility, as obtained via a verbal interview
with the subject or from the subject's medical records. Double barrier method: condom
and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal
agent (foam/gel/film/cream/suppository)

- COPD Diagnosis: An established clinical history of COPD in accordance with the
definition by the American Thoracic Society/European Respiratory Society

- Smoking History: Current or former cigarette smokers with a history of cigarette
smoking of >=10 pack-years at screening (visit 1) [number of pack years = (number of
cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10
years, or 10 cigarettes per day for 20 years)]. Previous smokers are defined as those
who have stopped smoking for at least 6 months prior to Visit 1. Note: Pipe and/or
cigar use cannot be used to calculate pack-year history

- Severity of COPD symptoms: A score of >=10 on the COPD Assessment Test (CAT) at
screening

- Severity of COPD Disease: A post-albuterol/salbutamol FEV1/ Forced Vital Capacity
(FVC) ratio of <0.70 at Screening

- Existing COPD maintenance treatment: Subject must be receiving daily maintenance
treatment for their COPD for at least 3 months prior to Screening. Note: Subjects
receiving only Pro re nata (PRN) COPD medications are not eligible

- History of Exacerbations: Subjects must demonstrate: a post-bronchodilator FEV1 <50%
predicted normal and a documented history of >= 1 moderate or severe COPD exacerbation
in the previous 12 months OR a post-bronchodilator 50% <=FEV1 < 80% predicted normal
and a documented history of >= 2 moderate exacerbations or a documented history of >=1
severe COPD exacerbation (hospitalized) in the previous 12 months. Note: Percent
predicted will be calculated using the European Respiratory Society Global Lung
Function Initiative reference equations. Note: A documented history of a COPD
exacerbation (e.g., medical record verification) is a medical record of worsening COPD
symptoms that required systemic/oral corticosteroids and/or antibiotics (for a
moderate exacerbation) or hospitalization (for a severe exacerbation). Prior use of
antibiotics alone does not qualify as an exacerbation history unless the use was
associated with treatment of worsening symptoms of COPD, such as increased dyspnea,
sputum volume, or sputum purulence (color). Subject verbal reports are not acceptable

- Liver function tests: alanine aminotransferase (ALT) <2x upper limit of normal (ULN);
alkaline phosphatase <=1.5xULN; bilirubin <=1.5xULN (isolated bilirubin >1.5 x ULN is
acceptable if bilirubin is fractionated and direct bilirubin <35%)

- French subjects: In France, a subject will be eligible for inclusion in this study
only if either affiliated to or a beneficiary of a social security category
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant
during the study

- Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of
asthma are eligible if they have a current diagnosis of COPD)

- Alpha1-antitrypsin deficiency: Subjects with Alpha1-antitrypsin deficiency as the
underlying cause of COPD

- Other respiratory disorders: Subjects with active tuberculosis, lung cancer,
significant bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension,
interstitial lung diseases or other active pulmonary diseases

- Lung resection: Subjects with lung volume reduction surgery within the 12 months prior
to Screening

- Risk Factors for Pneumonia: immune suppression (e.g. human immunodeficiency virus
[HIV], Lupus) or other risk factors for pneumonia (e.g. neurological disorders
affecting control of the upper airway, such as Parkinson's Disease, Myasthenia
Gravis). Patients at potentially high risk (e.g. very low BMI, severely malnourished,
or very low FEV1) will only be included at the discretion of the Investigator

- Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least
14 days prior to Screening and at least 30 days following the last dose of
oral/systemic corticosteroids (if applicable). In addition, any subject that
experiences pneumonia and/or moderate or severe COPD exacerbation during the run-in
period will be excluded

- Other Respiratory tract infections that have not resolved at least 7 days prior to
screening

- Abnormal Chest x-ray(CXR): Chest x-ray (posteroanterior and lateral) reveals evidence
of pneumonia or a clinically significant abnormality not believed to be due to the
presence of COPD, or another condition that would hinder the ability to detect an
infiltrate on CXR (e.g. significant cardiomegaly, pleural effusion or scarring). All
subjects will have a chest x-ray at Screening Visit 1 (or historical radiograph or
computerised tomography (CT) scan obtained within 3 months prior to screening) that
will be over-read by a central vendor. Note: Subjects who have experienced pneumonia
and/or moderate or severe COPD exacerbation within 3 months of screening must provide
a post pneumonia/exacerbation chest x-ray to be over-read by the central vendor or
have a chest x-ray conducted at screening. For sites in Germany: If a chest x-ray (or
CT scan) within 3 months prior to Screening (Visit 1) is not available, approval to
conduct a diagnostic chest x-ray will need to be obtained from the Federal Office for
Radiation Protection (Bundesamt für Strahlenschutz [BfS])

- Other diseases/abnormalities: Subjects with historical or current evidence of
clinically significant cardiovascular, neurological, psychiatric, renal, hepatic,
immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin,
sensory, endocrine (including uncontrolled diabetes or thyroid disease) or
hematological abnormalities that are uncontrolled. Significant is defined as any
disease that, in the opinion of the Investigator, would put the safety of the subject
at risk through participation, or which would affect the efficacy or safety analysis
if the disease/condition exacerbated during the study

- Unstable liver disease as defined by the presence of ascites, encephalopathy,
coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice,
cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or
asymptomatic gallstones).

- Note: Chronic stable hepatitis B and C are acceptable if the subject otherwise meets
entry criteria

- Unstable or life threatening cardiac disease: subjects with any of the following at
Screening (Visit 1) would be excluded: Myocardial infarction or unstable angina in the
last 6 months; Unstable or life threatening cardiac arrhythmia requiring intervention
in the last 3 months; New York Heart Association (NYHA) Class IV Heart failure

- Abnormal and clinically significant 12-Lead Electrocardiogram (ECG) finding:
Investigators will be provided with ECG reviews conducted by a centralized independent
cardiologist to assist in evaluation of subject eligibility. The Principal
Investigator will determine the clinical significance of each abnormal ECG finding in
relation to the subject's medical history and exclude subjects who would be at undue
risk by participating in the trial. An abnormal and clinically significant finding
that would preclude a subject from entering the trial is defined as a 12-lead tracing
that is interpreted as, but not limited to, any of the following: atrial fibrillation
(AF) with rapid ventricular rate >120 beats per minute); sustained or nonsustained
ventricular tachycardia (VT); Second degree heart block Mobitz type II and third
degree heart block (unless pacemaker or defibrillator had been inserted); QT interval
corrected for heart rate (QTcF) >=500 milliseconds (msec) in patients with QRS <120
msec and QTcF >=530 msec in patients with QRS >=120 msec

- Contraindications: A history of allergy or hypersensitivity to any corticosteroid,
anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or
magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic
hypertrophy or bladder neck obstruction that, in the opinion of the Investigator
contraindicates study participation

- Cancer: Subjects with carcinoma that has not been in complete remission for at least 5
years. Subjects who have had carcinoma in situ of the cervix, squamous cell carcinoma
and basal cell carcinoma of the skin would not be excluded based on the 5 year waiting
period if the subject has been considered cured by treatment

- Oxygen therapy: Use of long-term oxygen therapy (LTOT) described as resting oxygen
therapy >3 Liter/minute (L/min) (Oxygen use =<3L/min flow is not exclusionary)

- Medication prior to spirometry: Subjects who are medically unable to withhold their
albuterol/salbutamol for the 4-hour period required prior to spirometry testing at
each study visit

- Pulmonary rehabilitation: Subjects who have participated in the acute phase of a
Pulmonary Rehabilitation Program within 4 weeks prior to Screening or subjects who
plan to enter the acute phase of a Pulmonary Rehabilitation Program during the study.
Subjects who are in the maintenance phase of a Pulmonary Rehabilitation Program are
not excluded

- Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug
abuse within the last 2 years

- Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study
procedures. Any infirmity, disability, or geographic location that would limit
compliance for scheduled visits

- Questionable validity of consent: Subjects with a history of psychiatric disease,
intellectual deficiency, poor motivation or other conditions that will limit the
validity of informed consent to participate in the study

- Affiliation with investigator site: Study investigators, sub-investigators, study
coordinators, employees of a participating investigator or study site, or immediate
family members of the aforementioned that is involved with this study

- Inability to read: In the opinion of the Investigator, any subject who is unable to
read and/or would not be able to complete study related materials

- Medication prior to screening: Use of the following medications within the following
time intervals prior to Screening (Visit 1) or during the study: Long term antibiotic
therapy Subjects receiving antibiotics for long term therapy are not eligible for the
study (Antibiotics are allowed for the short term treatment of an exacerbation or for
short term treatment of other acute infections during the study); Systemic, Oral,
parenteral corticosteroids 30 days (Except during the study oral/systemic
corticosteroids may be used to treat COPD exacerbations/pneumonia) Intra-articular
injections are allowed; Any other investigational drug (30 days or 5 half lives
whichever is longer)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/06/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/07/2017
Sample size
Target
Accrual to date
Final
10355
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Concord
Recruitment hospital [2] 0 0
GSK Investigational Site - Gosford
Recruitment hospital [3] 0 0
GSK Investigational Site - Maroubra
Recruitment hospital [4] 0 0
GSK Investigational Site - Westmead
Recruitment hospital [5] 0 0
GSK Investigational Site - Cairns
Recruitment hospital [6] 0 0
GSK Investigational Site - Carina Heights
Recruitment hospital [7] 0 0
GSK Investigational Site - Adelaide
Recruitment hospital [8] 0 0
GSK Investigational Site - Daw Park
Recruitment hospital [9] 0 0
GSK Investigational Site - Clayton
Recruitment hospital [10] 0 0
GSK Investigational Site - Footscray
Recruitment hospital [11] 0 0
GSK Investigational Site - Frankston
Recruitment hospital [12] 0 0
GSK Investigational Site - Geelong
Recruitment hospital [13] 0 0
GSK Investigational Site - Hamilton
Recruitment hospital [14] 0 0
GSK Investigational Site - Murdoch
Recruitment hospital [15] 0 0
GSK Investigational Site - Nedlands
Recruitment hospital [16] 0 0
GSK Investigational Site - Liverpool
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2250 - Gosford
Recruitment postcode(s) [3] 0 0
2035 - Maroubra
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
4870 - Cairns
Recruitment postcode(s) [6] 0 0
4152 - Carina Heights
Recruitment postcode(s) [7] 0 0
5000 - Adelaide
Recruitment postcode(s) [8] 0 0
5041 - Daw Park
Recruitment postcode(s) [9] 0 0
3168 - Clayton
Recruitment postcode(s) [10] 0 0
3011 - Footscray
Recruitment postcode(s) [11] 0 0
3199 - Frankston
Recruitment postcode(s) [12] 0 0
3220 - Geelong
Recruitment postcode(s) [13] 0 0
3300 - Hamilton
Recruitment postcode(s) [14] 0 0
6964 - Murdoch
Recruitment postcode(s) [15] 0 0
6009 - Nedlands
Recruitment postcode(s) [16] 0 0
2107 - Liverpool
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Idaho
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Indiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Iowa
Country [12] 0 0
United States of America
State/province [12] 0 0
Kansas
Country [13] 0 0
United States of America
State/province [13] 0 0
Kentucky
Country [14] 0 0
United States of America
State/province [14] 0 0
Louisiana
Country [15] 0 0
United States of America
State/province [15] 0 0
Maine
Country [16] 0 0
United States of America
State/province [16] 0 0
Maryland
Country [17] 0 0
United States of America
State/province [17] 0 0
Massachusetts
Country [18] 0 0
United States of America
State/province [18] 0 0
Michigan
Country [19] 0 0
United States of America
State/province [19] 0 0
Minnesota
Country [20] 0 0
United States of America
State/province [20] 0 0
Mississippi
Country [21] 0 0
United States of America
State/province [21] 0 0
Missouri
Country [22] 0 0
United States of America
State/province [22] 0 0
Montana
Country [23] 0 0
United States of America
State/province [23] 0 0
Nebraska
Country [24] 0 0
United States of America
State/province [24] 0 0
Nevada
Country [25] 0 0
United States of America
State/province [25] 0 0
New Jersey
Country [26] 0 0
United States of America
State/province [26] 0 0
New Mexico
Country [27] 0 0
United States of America
State/province [27] 0 0
New York
Country [28] 0 0
United States of America
State/province [28] 0 0
North Carolina
Country [29] 0 0
United States of America
State/province [29] 0 0
Ohio
Country [30] 0 0
United States of America
State/province [30] 0 0
Oregon
Country [31] 0 0
United States of America
State/province [31] 0 0
Pennsylvania
Country [32] 0 0
United States of America
State/province [32] 0 0
Rhode Island
Country [33] 0 0
United States of America
State/province [33] 0 0
South Carolina
Country [34] 0 0
United States of America
State/province [34] 0 0
South Dakota
Country [35] 0 0
United States of America
State/province [35] 0 0
Tennessee
Country [36] 0 0
United States of America
State/province [36] 0 0
Texas
Country [37] 0 0
United States of America
State/province [37] 0 0
Virginia
Country [38] 0 0
United States of America
State/province [38] 0 0
Washington
Country [39] 0 0
Argentina
State/province [39] 0 0
Buenos Aires
Country [40] 0 0
Argentina
State/province [40] 0 0
Córdova
Country [41] 0 0
Argentina
State/province [41] 0 0
Entre Ríos
Country [42] 0 0
Argentina
State/province [42] 0 0
Mendoza
Country [43] 0 0
Argentina
State/province [43] 0 0
Santa Fe
Country [44] 0 0
Argentina
State/province [44] 0 0
Tucumán
Country [45] 0 0
Argentina
State/province [45] 0 0
Berazategui, Buenos Aires
Country [46] 0 0
Argentina
State/province [46] 0 0
Berazategui
Country [47] 0 0
Argentina
State/province [47] 0 0
Capital Federal
Country [48] 0 0
Argentina
State/province [48] 0 0
Ciudad Autonoma de Buenis Aires
Country [49] 0 0
Argentina
State/province [49] 0 0
Ciudad Autónoma de Buenos Aires
Country [50] 0 0
Argentina
State/province [50] 0 0
Cordoba
Country [51] 0 0
Argentina
State/province [51] 0 0
Coronel Suarez
Country [52] 0 0
Argentina
State/province [52] 0 0
Monte Grande
Country [53] 0 0
Argentina
State/province [53] 0 0
Salta
Country [54] 0 0
Argentina
State/province [54] 0 0
San Miguel de Tucumán
Country [55] 0 0
Argentina
State/province [55] 0 0
Santa Rosa
Country [56] 0 0
Austria
State/province [56] 0 0
Feldbach
Country [57] 0 0
Austria
State/province [57] 0 0
Feldkirch
Country [58] 0 0
Austria
State/province [58] 0 0
Grieskirchen
Country [59] 0 0
Austria
State/province [59] 0 0
Thalheim bei Wels
Country [60] 0 0
Austria
State/province [60] 0 0
Vienna
Country [61] 0 0
Belgium
State/province [61] 0 0
Antwerpen
Country [62] 0 0
Belgium
State/province [62] 0 0
Brugge
Country [63] 0 0
Belgium
State/province [63] 0 0
Brussels
Country [64] 0 0
Belgium
State/province [64] 0 0
Erpent
Country [65] 0 0
Belgium
State/province [65] 0 0
Genk
Country [66] 0 0
Belgium
State/province [66] 0 0
Gent
Country [67] 0 0
Belgium
State/province [67] 0 0
Gilly
Country [68] 0 0
Belgium
State/province [68] 0 0
Hasselt
Country [69] 0 0
Belgium
State/province [69] 0 0
Liège
Country [70] 0 0
Belgium
State/province [70] 0 0
Malmedy
Country [71] 0 0
Belgium
State/province [71] 0 0
Mechelen
Country [72] 0 0
Belgium
State/province [72] 0 0
Montigny-Le-Tilleul
Country [73] 0 0
Belgium
State/province [73] 0 0
Oostende
Country [74] 0 0
Belgium
State/province [74] 0 0
Roeselaere
Country [75] 0 0
Belgium
State/province [75] 0 0
Turnhout
Country [76] 0 0
Brazil
State/province [76] 0 0
Pernambuco
Country [77] 0 0
Brazil
State/province [77] 0 0
Rio Grande Do Sul
Country [78] 0 0
Brazil
State/province [78] 0 0
Santa Catarina
Country [79] 0 0
Brazil
State/province [79] 0 0
Rio de Janeiro
Country [80] 0 0
Brazil
State/province [80] 0 0
São Paulo
Country [81] 0 0
Canada
State/province [81] 0 0
Alberta
Country [82] 0 0
Canada
State/province [82] 0 0
Manitoba
Country [83] 0 0
Canada
State/province [83] 0 0
New Brunswick
Country [84] 0 0
Canada
State/province [84] 0 0
Nova Scotia
Country [85] 0 0
Canada
State/province [85] 0 0
Ontario
Country [86] 0 0
Canada
State/province [86] 0 0
Quebec
Country [87] 0 0
Chile
State/province [87] 0 0
Región Del Biobio
Country [88] 0 0
Chile
State/province [88] 0 0
Región Del Maule
Country [89] 0 0
Chile
State/province [89] 0 0
Región Metro De Santiago
Country [90] 0 0
Chile
State/province [90] 0 0
Valparaíso
Country [91] 0 0
Chile
State/province [91] 0 0
Santiago
Country [92] 0 0
Chile
State/province [92] 0 0
Talcahuano
Country [93] 0 0
Chile
State/province [93] 0 0
Viña del Mar
Country [94] 0 0
China
State/province [94] 0 0
Guangdong
Country [95] 0 0
China
State/province [95] 0 0
Guangxi
Country [96] 0 0
China
State/province [96] 0 0
Hainan
Country [97] 0 0
China
State/province [97] 0 0
Hebei
Country [98] 0 0
China
State/province [98] 0 0
Jiangsu
Country [99] 0 0
China
State/province [99] 0 0
Jiangxi
Country [100] 0 0
China
State/province [100] 0 0
Jilin
Country [101] 0 0
China
State/province [101] 0 0
Liaoning
Country [102] 0 0
China
State/province [102] 0 0
Ningxia
Country [103] 0 0
China
State/province [103] 0 0
Shandong
Country [104] 0 0
China
State/province [104] 0 0
Shanxi
Country [105] 0 0
China
State/province [105] 0 0
Sichuan
Country [106] 0 0
China
State/province [106] 0 0
Zhejiang
Country [107] 0 0
China
State/province [107] 0 0
Beijing
Country [108] 0 0
China
State/province [108] 0 0
Changsha
Country [109] 0 0
China
State/province [109] 0 0
Chongqing
Country [110] 0 0
China
State/province [110] 0 0
Fuzhou
Country [111] 0 0
China
State/province [111] 0 0
Guangzhou
Country [112] 0 0
China
State/province [112] 0 0
Nanchang
Country [113] 0 0
China
State/province [113] 0 0
Shanghai
Country [114] 0 0
China
State/province [114] 0 0
Tianjin
Country [115] 0 0
China
State/province [115] 0 0
Wuxi
Country [116] 0 0
Colombia
State/province [116] 0 0
Barranquilla
Country [117] 0 0
Colombia
State/province [117] 0 0
Bogota
Country [118] 0 0
Colombia
State/province [118] 0 0
Bogotá
Country [119] 0 0
Colombia
State/province [119] 0 0
Medellin
Country [120] 0 0
Czechia
State/province [120] 0 0
Benesov
Country [121] 0 0
Czechia
State/province [121] 0 0
Brandys nad Labem
Country [122] 0 0
Czechia
State/province [122] 0 0
Cvikov
Country [123] 0 0
Czechia
State/province [123] 0 0
Holesov
Country [124] 0 0
Czechia
State/province [124] 0 0
Hradec Kralove
Country [125] 0 0
Czechia
State/province [125] 0 0
Jaromer
Country [126] 0 0
Czechia
State/province [126] 0 0
Olomouc
Country [127] 0 0
Czechia
State/province [127] 0 0
Ostrava - Poruba
Country [128] 0 0
Czechia
State/province [128] 0 0
Plzen
Country [129] 0 0
Czechia
State/province [129] 0 0
Praha 5
Country [130] 0 0
Czechia
State/province [130] 0 0
Praha 8
Country [131] 0 0
Czechia
State/province [131] 0 0
Tabor
Country [132] 0 0
Czechia
State/province [132] 0 0
Teplice
Country [133] 0 0
Czechia
State/province [133] 0 0
Trebic
Country [134] 0 0
Denmark
State/province [134] 0 0
Aalborg
Country [135] 0 0
Denmark
State/province [135] 0 0
Aarhus C
Country [136] 0 0
Denmark
State/province [136] 0 0
Hellerup
Country [137] 0 0
Denmark
State/province [137] 0 0
Hvidovre
Country [138] 0 0
Denmark
State/province [138] 0 0
Kolding
Country [139] 0 0
Denmark
State/province [139] 0 0
Odense C
Country [140] 0 0
Denmark
State/province [140] 0 0
Roskilde
Country [141] 0 0
Denmark
State/province [141] 0 0
Sønderborg
Country [142] 0 0
Finland
State/province [142] 0 0
Espoo
Country [143] 0 0
Finland
State/province [143] 0 0
Helsinki
Country [144] 0 0
Finland
State/province [144] 0 0
Jyvaskyla
Country [145] 0 0
Finland
State/province [145] 0 0
Lohja
Country [146] 0 0
Finland
State/province [146] 0 0
Tampere
Country [147] 0 0
Finland
State/province [147] 0 0
Turku
Country [148] 0 0
France
State/province [148] 0 0
Bayonne cedex
Country [149] 0 0
France
State/province [149] 0 0
Brest Cedex
Country [150] 0 0
France
State/province [150] 0 0
Briis-sous-Forge
Country [151] 0 0
France
State/province [151] 0 0
Grenoble cedex 9
Country [152] 0 0
France
State/province [152] 0 0
Le Mans
Country [153] 0 0
France
State/province [153] 0 0
Lyon cedex 04
Country [154] 0 0
France
State/province [154] 0 0
Marseille cedex 03
Country [155] 0 0
France
State/province [155] 0 0
Montauban cedex
Country [156] 0 0
France
State/province [156] 0 0
Montpellier cedex 5
Country [157] 0 0
France
State/province [157] 0 0
Nimes
Country [158] 0 0
France
State/province [158] 0 0
Orléans cedex 2
Country [159] 0 0
France
State/province [159] 0 0
Paris
Country [160] 0 0
France
State/province [160] 0 0
Perpignan
Country [161] 0 0
France
State/province [161] 0 0
Pessac cedex
Country [162] 0 0
France
State/province [162] 0 0
Pringy cedex
Country [163] 0 0
France
State/province [163] 0 0
Rennes Cedex 9
Country [164] 0 0
France
State/province [164] 0 0
Strasbourg cedex
Country [165] 0 0
France
State/province [165] 0 0
Toulon
Country [166] 0 0
France
State/province [166] 0 0
Vandoeuvre-les-Nancy
Country [167] 0 0
Germany
State/province [167] 0 0
Baden-Wuerttemberg
Country [168] 0 0
Germany
State/province [168] 0 0
Bayern
Country [169] 0 0
Germany
State/province [169] 0 0
Brandenburg
Country [170] 0 0
Germany
State/province [170] 0 0
Hessen
Country [171] 0 0
Germany
State/province [171] 0 0
Niedersachsen
Country [172] 0 0
Germany
State/province [172] 0 0
Nordrhein-Westfalen
Country [173] 0 0
Germany
State/province [173] 0 0
Rheinland-Pfalz
Country [174] 0 0
Germany
State/province [174] 0 0
Saarland
Country [175] 0 0
Germany
State/province [175] 0 0
Sachsen-Anhalt
Country [176] 0 0
Germany
State/province [176] 0 0
Sachsen
Country [177] 0 0
Germany
State/province [177] 0 0
Schleswig-Holstein
Country [178] 0 0
Germany
State/province [178] 0 0
Thueringen
Country [179] 0 0
Germany
State/province [179] 0 0
Berlin
Country [180] 0 0
Germany
State/province [180] 0 0
Deggendorf
Country [181] 0 0
Germany
State/province [181] 0 0
Hamburg
Country [182] 0 0
Germany
State/province [182] 0 0
Witten
Country [183] 0 0
Hong Kong
State/province [183] 0 0
Kwun Tong
Country [184] 0 0
Hong Kong
State/province [184] 0 0
Lai Chi Kok
Country [185] 0 0
Hong Kong
State/province [185] 0 0
Pokfulam
Country [186] 0 0
Hong Kong
State/province [186] 0 0
Shatin
Country [187] 0 0
Hong Kong
State/province [187] 0 0
Tuen Mun
Country [188] 0 0
Israel
State/province [188] 0 0
Afula
Country [189] 0 0
Israel
State/province [189] 0 0
Ashkelon
Country [190] 0 0
Israel
State/province [190] 0 0
Haifa
Country [191] 0 0
Israel
State/province [191] 0 0
Holon
Country [192] 0 0
Israel
State/province [192] 0 0
Jerusalem
Country [193] 0 0
Israel
State/province [193] 0 0
Kfar-Saba
Country [194] 0 0
Israel
State/province [194] 0 0
Petah Tikva
Country [195] 0 0
Israel
State/province [195] 0 0
Ramat Gan
Country [196] 0 0
Israel
State/province [196] 0 0
Rehovot
Country [197] 0 0
Israel
State/province [197] 0 0
Tel Aviv
Country [198] 0 0
Israel
State/province [198] 0 0
Tel-Aviv
Country [199] 0 0
Israel
State/province [199] 0 0
Zrifin
Country [200] 0 0
Japan
State/province [200] 0 0
Aichi
Country [201] 0 0
Japan
State/province [201] 0 0
Chiba
Country [202] 0 0
Japan
State/province [202] 0 0
Ehime
Country [203] 0 0
Japan
State/province [203] 0 0
Fukuoka
Country [204] 0 0
Japan
State/province [204] 0 0
Gifu
Country [205] 0 0
Japan
State/province [205] 0 0
Gunma
Country [206] 0 0
Japan
State/province [206] 0 0
Hiroshima
Country [207] 0 0
Japan
State/province [207] 0 0
Hokkaido
Country [208] 0 0
Japan
State/province [208] 0 0
Hyogo
Country [209] 0 0
Japan
State/province [209] 0 0
Ibaraki
Country [210] 0 0
Japan
State/province [210] 0 0
Ishikawa
Country [211] 0 0
Japan
State/province [211] 0 0
Iwate
Country [212] 0 0
Japan
State/province [212] 0 0
Kagawa
Country [213] 0 0
Japan
State/province [213] 0 0
Kanagawa
Country [214] 0 0
Japan
State/province [214] 0 0
Kochi
Country [215] 0 0
Japan
State/province [215] 0 0
Kumamoto
Country [216] 0 0
Japan
State/province [216] 0 0
Kyoto
Country [217] 0 0
Japan
State/province [217] 0 0
Mie
Country [218] 0 0
Japan
State/province [218] 0 0
Miyagi
Country [219] 0 0
Japan
State/province [219] 0 0
Nagano
Country [220] 0 0
Japan
State/province [220] 0 0
Niigata
Country [221] 0 0
Japan
State/province [221] 0 0
Oita
Country [222] 0 0
Japan
State/province [222] 0 0
Okayama
Country [223] 0 0
Japan
State/province [223] 0 0
Okinawa
Country [224] 0 0
Japan
State/province [224] 0 0
Osaka
Country [225] 0 0
Japan
State/province [225] 0 0
Saitama
Country [226] 0 0
Japan
State/province [226] 0 0
Shizuoka
Country [227] 0 0
Japan
State/province [227] 0 0
Tochigi
Country [228] 0 0
Japan
State/province [228] 0 0
Tokyo
Country [229] 0 0
Japan
State/province [229] 0 0
Toyama
Country [230] 0 0
Japan
State/province [230] 0 0
Wakayama
Country [231] 0 0
Japan
State/province [231] 0 0
Yamagata
Country [232] 0 0
Japan
State/province [232] 0 0
Yamanashi
Country [233] 0 0
Korea, Republic of
State/province [233] 0 0
Bucheon city, Gyenggi-do
Country [234] 0 0
Korea, Republic of
State/province [234] 0 0
Cheongju-si, Chungcheongbuk-do
Country [235] 0 0
Korea, Republic of
State/province [235] 0 0
Gyeonggi-do
Country [236] 0 0
Korea, Republic of
State/province [236] 0 0
Incheon
Country [237] 0 0
Korea, Republic of
State/province [237] 0 0
Jeonju-si
Country [238] 0 0
Korea, Republic of
State/province [238] 0 0
Kangwon-do
Country [239] 0 0
Korea, Republic of
State/province [239] 0 0
Seoul
Country [240] 0 0
Korea, Republic of
State/province [240] 0 0
Suwon
Country [241] 0 0
Netherlands
State/province [241] 0 0
Alkmaar
Country [242] 0 0
Netherlands
State/province [242] 0 0
Almelo
Country [243] 0 0
Netherlands
State/province [243] 0 0
Assen
Country [244] 0 0
Netherlands
State/province [244] 0 0
Beek
Country [245] 0 0
Netherlands
State/province [245] 0 0
Breda
Country [246] 0 0
Netherlands
State/province [246] 0 0
Den Bosch
Country [247] 0 0
Netherlands
State/province [247] 0 0
Dordrecht
Country [248] 0 0
Netherlands
State/province [248] 0 0
Eindhoven
Country [249] 0 0
Netherlands
State/province [249] 0 0
Enschede
Country [250] 0 0
Netherlands
State/province [250] 0 0
Groningen
Country [251] 0 0
Netherlands
State/province [251] 0 0
Harderwijk
Country [252] 0 0
Netherlands
State/province [252] 0 0
Helmond
Country [253] 0 0
Netherlands
State/province [253] 0 0
Hoofddorp
Country [254] 0 0
Netherlands
State/province [254] 0 0
Hoorn
Country [255] 0 0
Netherlands
State/province [255] 0 0
Kloosterhaar
Country [256] 0 0
Netherlands
State/province [256] 0 0
Leeuwarden
Country [257] 0 0
Netherlands
State/province [257] 0 0
Nieuwegein
Country [258] 0 0
Netherlands
State/province [258] 0 0
Rotterdam
Country [259] 0 0
Netherlands
State/province [259] 0 0
Sneek
Country [260] 0 0
Netherlands
State/province [260] 0 0
Spijkenisse
Country [261] 0 0
Netherlands
State/province [261] 0 0
Veldhoven
Country [262] 0 0
Netherlands
State/province [262] 0 0
Zutphen
Country [263] 0 0
Netherlands
State/province [263] 0 0
Zwolle
Country [264] 0 0
New Zealand
State/province [264] 0 0
Auckland
Country [265] 0 0
New Zealand
State/province [265] 0 0
Dunedin
Country [266] 0 0
New Zealand
State/province [266] 0 0
Newtown, Wellington
Country [267] 0 0
New Zealand
State/province [267] 0 0
Tauranga
Country [268] 0 0
New Zealand
State/province [268] 0 0
Wellington
Country [269] 0 0
Norway
State/province [269] 0 0
Bodø
Country [270] 0 0
Norway
State/province [270] 0 0
Fredrikstad
Country [271] 0 0
Norway
State/province [271] 0 0
Hakadal
Country [272] 0 0
Norway
State/province [272] 0 0
Kløfta
Country [273] 0 0
Norway
State/province [273] 0 0
Levanger
Country [274] 0 0
Norway
State/province [274] 0 0
Oslo
Country [275] 0 0
Norway
State/province [275] 0 0
Stavanger
Country [276] 0 0
Norway
State/province [276] 0 0
Trondheim
Country [277] 0 0
Peru
State/province [277] 0 0
Lima
Country [278] 0 0
Philippines
State/province [278] 0 0
Caloocan City
Country [279] 0 0
Philippines
State/province [279] 0 0
Iloilo
Country [280] 0 0
Philippines
State/province [280] 0 0
Jaro, Iloilo City
Country [281] 0 0
Philippines
State/province [281] 0 0
Pasig
Country [282] 0 0
Philippines
State/province [282] 0 0
Quezon City
Country [283] 0 0
Poland
State/province [283] 0 0
Bialystok
Country [284] 0 0
Poland
State/province [284] 0 0
Ostrowiec Swietokrzyski
Country [285] 0 0
Poland
State/province [285] 0 0
Sopot
Country [286] 0 0
Poland
State/province [286] 0 0
Szczecin
Country [287] 0 0
Poland
State/province [287] 0 0
Tarnów
Country [288] 0 0
Poland
State/province [288] 0 0
Zgierz
Country [289] 0 0
Puerto Rico
State/province [289] 0 0
Guaynabo
Country [290] 0 0
Puerto Rico
State/province [290] 0 0
Mayaguez
Country [291] 0 0
Puerto Rico
State/province [291] 0 0
Ponce
Country [292] 0 0
Puerto Rico
State/province [292] 0 0
San Juan
Country [293] 0 0
Romania
State/province [293] 0 0
Braila
Country [294] 0 0
Romania
State/province [294] 0 0
Brasov
Country [295] 0 0
Romania
State/province [295] 0 0
Bucharest
Country [296] 0 0
Romania
State/province [296] 0 0
Comuna Alexandru Cel Bun
Country [297] 0 0
Romania
State/province [297] 0 0
Constanta
Country [298] 0 0
Romania
State/province [298] 0 0
Ploiesti
Country [299] 0 0
Romania
State/province [299] 0 0
Ramnicu Valcea
Country [300] 0 0
Russian Federation
State/province [300] 0 0
Barnaul
Country [301] 0 0
Russian Federation
State/province [301] 0 0
Belgorod
Country [302] 0 0
Russian Federation
State/province [302] 0 0
Blagoveshchensk
Country [303] 0 0
Russian Federation
State/province [303] 0 0
Chita
Country [304] 0 0
Russian Federation
State/province [304] 0 0
Ekaterinburg
Country [305] 0 0
Russian Federation
State/province [305] 0 0
Ivanovo
Country [306] 0 0
Russian Federation
State/province [306] 0 0
Kazan
Country [307] 0 0
Russian Federation
State/province [307] 0 0
Krasnodar
Country [308] 0 0
Russian Federation
State/province [308] 0 0
Krasnoyarsk
Country [309] 0 0
Russian Federation
State/province [309] 0 0
Moscow
Country [310] 0 0
Russian Federation
State/province [310] 0 0
Novgorod
Country [311] 0 0
Russian Federation
State/province [311] 0 0
Novosibirsk
Country [312] 0 0
Russian Federation
State/province [312] 0 0
Petrozavodsk
Country [313] 0 0
Russian Federation
State/province [313] 0 0
Pyatigorsk
Country [314] 0 0
Russian Federation
State/province [314] 0 0
Ryazan
Country [315] 0 0
Russian Federation
State/province [315] 0 0
Saint-Petersburg
Country [316] 0 0
Russian Federation
State/province [316] 0 0
Saratov
Country [317] 0 0
Russian Federation
State/province [317] 0 0
St. Petersburg
Country [318] 0 0
Russian Federation
State/province [318] 0 0
Stavropol
Country [319] 0 0
Russian Federation
State/province [319] 0 0
Tomsk
Country [320] 0 0
Russian Federation
State/province [320] 0 0
Ulan-Ude
Country [321] 0 0
Russian Federation
State/province [321] 0 0
Ulyanovsk
Country [322] 0 0
Russian Federation
State/province [322] 0 0
Vladimir
Country [323] 0 0
Russian Federation
State/province [323] 0 0
Vladivostok
Country [324] 0 0
Russian Federation
State/province [324] 0 0
Volgodonsk
Country [325] 0 0
Russian Federation
State/province [325] 0 0
Voronezh
Country [326] 0 0
Russian Federation
State/province [326] 0 0
Vsevolozhsk, Leningrad Region
Country [327] 0 0
Russian Federation
State/province [327] 0 0
Yaroslavl
Country [328] 0 0
Singapore
State/province [328] 0 0
Singapore
Country [329] 0 0
South Africa
State/province [329] 0 0
Gauteng
Country [330] 0 0
South Africa
State/province [330] 0 0
Mpumalanga
Country [331] 0 0
South Africa
State/province [331] 0 0
Amanzimtoti
Country [332] 0 0
South Africa
State/province [332] 0 0
Bellville
Country [333] 0 0
South Africa
State/province [333] 0 0
Bloemfontein
Country [334] 0 0
South Africa
State/province [334] 0 0
Boksburg North
Country [335] 0 0
South Africa
State/province [335] 0 0
Cape Town
Country [336] 0 0
South Africa
State/province [336] 0 0
CapeTown
Country [337] 0 0
South Africa
State/province [337] 0 0
Durban
Country [338] 0 0
South Africa
State/province [338] 0 0
Gatesville
Country [339] 0 0
South Africa
State/province [339] 0 0
Johannesburg
Country [340] 0 0
South Africa
State/province [340] 0 0
Korsten
Country [341] 0 0
South Africa
State/province [341] 0 0
Mowbray
Country [342] 0 0
South Africa
State/province [342] 0 0
Paarl
Country [343] 0 0
South Africa
State/province [343] 0 0
Panorama
Country [344] 0 0
South Africa
State/province [344] 0 0
Tygerberg
Country [345] 0 0
Spain
State/province [345] 0 0
Andalucia
Country [346] 0 0
Spain
State/province [346] 0 0
Cantabria
Country [347] 0 0
Spain
State/province [347] 0 0
Catalonia
Country [348] 0 0
Spain
State/province [348] 0 0
(Badalona) Barcelona
Country [349] 0 0
Spain
State/province [349] 0 0
(Barakaldo) Vizcaya
Country [350] 0 0
Spain
State/province [350] 0 0
Alicante
Country [351] 0 0
Spain
State/province [351] 0 0
Alzira/Valencia
Country [352] 0 0
Spain
State/province [352] 0 0
Barcelona
Country [353] 0 0
Spain
State/province [353] 0 0
Basurto/Bilbao
Country [354] 0 0
Spain
State/province [354] 0 0
Burgos
Country [355] 0 0
Spain
State/province [355] 0 0
Centelles (Barcelona)
Country [356] 0 0
Spain
State/province [356] 0 0
Coslada
Country [357] 0 0
Spain
State/province [357] 0 0
Cáceres
Country [358] 0 0
Spain
State/province [358] 0 0
Gerona
Country [359] 0 0
Spain
State/province [359] 0 0
Girona
Country [360] 0 0
Spain
State/province [360] 0 0
L'Hospitalet de Llobregat
Country [361] 0 0
Spain
State/province [361] 0 0
La Coruña
Country [362] 0 0
Spain
State/province [362] 0 0
La Roca Del Valles (Barcelona)
Country [363] 0 0
Spain
State/province [363] 0 0
Lleida
Country [364] 0 0
Spain
State/province [364] 0 0
Madrid
Country [365] 0 0
Spain
State/province [365] 0 0
Mataró
Country [366] 0 0
Spain
State/province [366] 0 0
Málaga
Country [367] 0 0
Spain
State/province [367] 0 0
Mérida (Badajoz)
Country [368] 0 0
Spain
State/province [368] 0 0
Oviedo
Country [369] 0 0
Spain
State/province [369] 0 0
Palma de Mallorca
Country [370] 0 0
Spain
State/province [370] 0 0
Pamplona
Country [371] 0 0
Spain
State/province [371] 0 0
Peralada( Girona)
Country [372] 0 0
Spain
State/province [372] 0 0
Petrer/Alicante
Country [373] 0 0
Spain
State/province [373] 0 0
Ponferrada (León)
Country [374] 0 0
Spain
State/province [374] 0 0
Pozuelo De Alarcón/Madrid
Country [375] 0 0
Spain
State/province [375] 0 0
Sabadell (Barcelona)
Country [376] 0 0
Spain
State/province [376] 0 0
Sagunto/Valencia
Country [377] 0 0
Spain
State/province [377] 0 0
Salamanca
Country [378] 0 0
Spain
State/province [378] 0 0
San Juan De Alicante
Country [379] 0 0
Spain
State/province [379] 0 0
San Sebastian de los Reyes
Country [380] 0 0
Spain
State/province [380] 0 0
Santander
Country [381] 0 0
Spain
State/province [381] 0 0
Santiago de Compostela
Country [382] 0 0
Spain
State/province [382] 0 0
Sevilla
Country [383] 0 0
Spain
State/province [383] 0 0
Tarragona
Country [384] 0 0
Spain
State/province [384] 0 0
Valencia
Country [385] 0 0
Spain
State/province [385] 0 0
Valladolid
Country [386] 0 0
Spain
State/province [386] 0 0
Vizcaya
Country [387] 0 0
Spain
State/province [387] 0 0
Zaragoza
Country [388] 0 0
Sweden
State/province [388] 0 0
Borås
Country [389] 0 0
Sweden
State/province [389] 0 0
Göteborg
Country [390] 0 0
Sweden
State/province [390] 0 0
Höllviken
Country [391] 0 0
Sweden
State/province [391] 0 0
Linköping
Country [392] 0 0
Sweden
State/province [392] 0 0
Luleå
Country [393] 0 0
Sweden
State/province [393] 0 0
Stockholm
Country [394] 0 0
Sweden
State/province [394] 0 0
Uppsala
Country [395] 0 0
Sweden
State/province [395] 0 0
Örebro
Country [396] 0 0
Sweden
State/province [396] 0 0
Östersund
Country [397] 0 0
Thailand
State/province [397] 0 0
Bangkok
Country [398] 0 0
Thailand
State/province [398] 0 0
Chiangmai
Country [399] 0 0
Thailand
State/province [399] 0 0
Khon Kaen
Country [400] 0 0
Thailand
State/province [400] 0 0
Muang
Country [401] 0 0
Thailand
State/province [401] 0 0
Nakhon Ratchasima
Country [402] 0 0
Thailand
State/province [402] 0 0
Nan
Country [403] 0 0
Thailand
State/province [403] 0 0
Songkla
Country [404] 0 0
Turkey
State/province [404] 0 0
Ankara
Country [405] 0 0
Turkey
State/province [405] 0 0
Istanbul
Country [406] 0 0
Turkey
State/province [406] 0 0
Izmir
Country [407] 0 0
Turkey
State/province [407] 0 0
Mersin
Country [408] 0 0
Ukraine
State/province [408] 0 0
Kharkiv
Country [409] 0 0
Ukraine
State/province [409] 0 0
Kiev
Country [410] 0 0
Ukraine
State/province [410] 0 0
Kyiv
Country [411] 0 0
Ukraine
State/province [411] 0 0
Mykolayiv
Country [412] 0 0
Ukraine
State/province [412] 0 0
Odesa
Country [413] 0 0
Ukraine
State/province [413] 0 0
Sumy
Country [414] 0 0
Ukraine
State/province [414] 0 0
Vinnytsia
Country [415] 0 0
United Kingdom
State/province [415] 0 0
Devon
Country [416] 0 0
United Kingdom
State/province [416] 0 0
Lanarkshire
Country [417] 0 0
United Kingdom
State/province [417] 0 0
Lancashire
Country [418] 0 0
United Kingdom
State/province [418] 0 0
Middlesex
Country [419] 0 0
United Kingdom
State/province [419] 0 0
Tyne & Wear
Country [420] 0 0
United Kingdom
State/province [420] 0 0
Wiltshire
Country [421] 0 0
United Kingdom
State/province [421] 0 0
Baillieston, Glasgow
Country [422] 0 0
United Kingdom
State/province [422] 0 0
Bradford
Country [423] 0 0
United Kingdom
State/province [423] 0 0
Cambridge
Country [424] 0 0
United Kingdom
State/province [424] 0 0
Chester
Country [425] 0 0
United Kingdom
State/province [425] 0 0
Crawley
Country [426] 0 0
United Kingdom
State/province [426] 0 0
Crownhill, Plymouth
Country [427] 0 0
United Kingdom
State/province [427] 0 0
Dundee, Scotland
Country [428] 0 0
United Kingdom
State/province [428] 0 0
Sidcup, Kent
Country [429] 0 0
United Kingdom
State/province [429] 0 0
Stockton-on-Tees
Country [430] 0 0
United Kingdom
State/province [430] 0 0
Trowbridge
Country [431] 0 0
Vietnam
State/province [431] 0 0
Ha Noi
Country [432] 0 0
Vietnam
State/province [432] 0 0
Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The study evaluates the efficacy of fluticasone furoate/umeclidinium bromide/vilanterol
(FF/UMEC/VI) to reduce the annual rate of moderate and severe exacerbations compared with
dual therapy of FF/VI or UMEC/VI in subjects with COPD. Published studies which assessed the
use of an 'open' triple therapy (use of Inhaled Corticosteroid [ICS]/ Long-acting Muscarinic
Receptor Antagonists [LAMA])/ Long Acting Beta-Agonist [LABA] delivered via multiple
inhalers) in moderate-severe COPD patients, reported improvements in lung function, Health
Related Quality of Life (HRQoL), hospitalization rates and rescue medication use, compared to
dual therapy (ICS/LABA) or LAMA alone. These studies have also shown similar safety profile
with dual or monotherapy doses for periods of up to one year. Given the clinical experience
with FF, UMEC and VI, and that the associated risks with these compounds are anticipated from
their known pharmacology, the potential benefit of a new therapy option in patients with
moderate to severe COPD supports the further development of the closed triple combination
(delivered via one inhaler). In the current study subjects meeting all inclusion/exclusion
criteria will complete 2-week run-in period; 52 week treatment period and a 1-week safety
follow-up period. Eligible subjects will be randomized to one of the following double-blind
treatment groups FF/UMEC/VI 100 micrograms (mcg)/62.5 mcg/25 mcg once daily (QD), FF/VI 100
mcg/25 mcg QD, or UMEC/VI 62.5 mcg/25 mcg QD
Trial website
https://clinicaltrials.gov/ct2/show/NCT02164513
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02164513