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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04072887




Registration number
NCT04072887
Ethics application status
Date submitted
7/08/2019
Date registered
28/08/2019
Date last updated
28/04/2023

Titles & IDs
Public title
Dose-range Finding Efficacy and Safety Study for QBW251 in COPD Patients
Scientific title
A 24-week Multi-center, Double-blind, Placebo Controlled Dose-range Finding Study to Investigate the Efficacy and Safety of Oral QBW251 in COPD Patients on Triple Inhaled Therapy (LABA / LAMA / ICS)
Secondary ID [1] 0 0
2018-003197-28
Secondary ID [2] 0 0
CQBW251B2201
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 - QBW251
Treatment: Drugs - Placebo
Treatment: Drugs - COPD maintenance background therapy

Experimental: QBW251 450 mg - QBW251 was orally administered 450 mg b.i.d for 24 weeks

Experimental: QBW251 300 mg - QBW251 was orally administered 300 mg b.i.d for 24 weeks

Experimental: QBW251 150 mg - QBW251 was orally administered 150 mg b.i.d for 24 weeks

Experimental: QBW251 75 mg - QBW251 was orally administered 75 mg b.i.d for 24 weeks

Experimental: QBW251 25 mg - QBW251 was orally administered 25 mg b.i.d for 24 weeks

Placebo comparator: Placebo - Placebo was orally administered b.i.d for 24 weeks


Treatment: Drugs: QBW251
QBW251 oral capsules (450, 300, 150, 75 and 25 mg) of identical appearance to ensure blinding administered twice a day (b.i.d) for 24 weeks

Treatment: Drugs: Placebo
Placebo oral capsules administered twice a day for 24 weeks

Treatment: Drugs: COPD maintenance background therapy
Combination of fluticasone furoate, vilanterol and umeclidinium bromide
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Week 12
Assessment method [1] 0 0
The primary efficacy analysis assessed the effect of QBW251 on the absolute change from baseline in trough FEV1 in liters on Week 12. Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline measurement was defined as the baseline visit pre-bronchodilator spirometry assessment. Change from baseline in the FEV1 mean scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + run-in FEV1 + airflow limitation severity + region + time interval + treatment\*time interval interaction + baseline score\*time interval interaction.
Timepoint [1] 0 0
Baseline and Week 12
Secondary outcome [1] 0 0
Change From Baseline in Forced Expiratory Volume in One Second (FEV1)
Assessment method [1] 0 0
The primary efficacy analysis assessed the effect of QBW251 on the absolute change from baseline in trough FEV1 in liters compared to placebo on Weeks 4, 8, 16, 20 and 24. Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline measurement was defined as the baseline visit pre-bronchodilator spirometry assessment. A positive trend for change from baseline in FEV1 across the dose range is considered a favorable outcome.
Timepoint [1] 0 0
Baseline, weeks 4, 8, 16, 20 and 24
Secondary outcome [2] 0 0
Change From Baseline in Evaluating Respiratory Symptoms (E-RS); Total Score
Assessment method [2] 0 0
The E-RS assesses overall daily respiratory COPD symptoms (Total score) and it is derived as the sum of 11 severity items; a higher scores indicate more severe symptoms. E-RS total score has a range of 0 to 40. Change from baseline in the E-RS Total weekly mean scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + run-in E-RS + airflow limitation severity + region + time interval + treatment\*time interval interaction + baseline score\*time interval interaction. The mean baseline E-RS Total score was the average of the corresponding daily scores from the run-in period. A negative change from baseline corresponds to improvement in symptoms severity.
Timepoint [2] 0 0
Baseline, weeks 12 and 24
Secondary outcome [3] 0 0
Change From Baseline in Evaluating Respiratory Symptoms (E-RS); Cough and Sputum Score
Assessment method [3] 0 0
The E-RS assesses both overall daily respiratory COPD symptoms (Total score) and specific respiratory symptoms using 3 subscales (Breathlessness, Cough \& Sputum, and Chest Symptoms). The E-RS comprises 11 severity items and higher scores indicate more severe symptoms. The Cough and Sputum subscale score has a range of 0 to 11 and was derived as the sum of items 2 - 4. Change from baseline in the E-RS Cough and Sputum weekly mean scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + run-in E-RS + airflow limitation severity + region + time interval + treatment\*time interval interaction + baseline score\*time interval interaction. The mean baseline E-RS Cough \& Sputum subscale score was the average of the corresponding daily scores from the run-in period. Lower scores in the change from baseline correspond to lower symptom severity.
Timepoint [3] 0 0
Baseline, weeks 12 and 24
Secondary outcome [4] 0 0
Number of Participants With a "Better" Change in the Patient Global Impression of Severity (PGI-S) From Baseline
Assessment method [4] 0 0
The PGI-S questionnaire is a patient-reported outcomes score that rates the severity of the respiratory symptoms and of cough and mucus. The change in severity scores (Better, No change and Worse) from baseline were reported at weeks 12 and 24. Thus, the number of participants with a Better change in the severity score are reported in the table below.
Timepoint [4] 0 0
Baseline, weeks 12 and 24
Secondary outcome [5] 0 0
Change From Baseline in the Cough and Sputum Assessment Questionnaire (CASA-Q)
Assessment method [5] 0 0
The CASA-Q is a validated questionnaire instrument used to measure cough and sputum production, and their impact in patients COPD and/or chronic bronchitis. It contains a total of 20 items on a 5-step scale distributed in 4 domains: Cough symptoms, Cough impact, Sputum symptoms and Sputum impact. All items are rescored from 1-5 to 0-4 and then reverse scored such that better responses have higher scores. The four domains are ranged from 0-100 where higher scores associated with fewer symptoms/less impact due to cough or sputum. Change from baseline in the CASA-Q cough and symptoms scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + run-in E-RS + airflow limitation severity + region + time interval + treatment\*time interval interaction + baseline score\*time interval interaction.
Timepoint [5] 0 0
Baseline, weeks 12 and 24
Secondary outcome [6] 0 0
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ)
Assessment method [6] 0 0
SGRQ measures health impairment and contains 50 items divided into three components: Symptoms, Activity and Impacts. A score was calculated for each component and a "Total" score was also calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of quality of life. Change from baseline in the SGRQ scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + baseline SGRQ score + airflow limitation severity + region + time interval + treatment\*time interval interaction + baseline score\*time interval interaction.
Timepoint [6] 0 0
Baseline, weeks 12 and 24
Secondary outcome [7] 0 0
Minimum Plasma Concentration (Cmin) for QBW251
Assessment method [7] 0 0
Venous whole blood samples were collected for pharmacokinetics characterization. Cmin was measured pre dose at all visits and was summarized using descriptive statistics. All concentrations below the lower limit of quantification (LLOQ) were treated as zero.
Timepoint [7] 0 0
Pre-dose on Days 15, 29, 57, 85, 113, 141 and 169
Secondary outcome [8] 0 0
Maximum Plasma Concentration (Cmax) for QBW251
Assessment method [8] 0 0
Venous whole blood samples were collected for pharmacokinetics characterization. Cmax was calculated from plasma concentration data using non-compartmental methods and summarized using descriptive statistics. Cmax was measured in the samples taken at 3 hours post-dose with the exception of the participants included in the Serial PK set on Days 1 and 15 for whom all samples (1, 2, 4, 6, and 8 hours post-dose) were taken into consideration for the measurement of Cmax. All concentrations below the lower limit of quantification (LLOQ) were treated as zero.
Timepoint [8] 0 0
Days 1, 15 and 169
Secondary outcome [9] 0 0
Maximum Plasma Concentration (Cmax) for QBW251 in Serial PK Set
Assessment method [9] 0 0
Venous whole blood samples were collected for pharmacokinetics characterization. Cmax was calculated from plasma concentration data using non-compartmental methods and summarized using descriptive statistics. All concentrations below the lower limit of quantification (LLOQ) were treated as zero.
Timepoint [9] 0 0
1, 2, 4, 6, and 8 hours post-dose on Days 1 and 15
Secondary outcome [10] 0 0
Area Under the Curve From Time 0 to 24 Hours (AUC0-24h) of QBW251 in Serial PK Set
Assessment method [10] 0 0
Venous whole blood samples were collected for pharmacokinetics characterization. AUC0-24h was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. All concentrations below the lower limit of quantification (LLOQ) were treated as zero.
Timepoint [10] 0 0
1, 2, 4, 6, and 8 hours post-dose on Days 1 and 15

Eligibility
Key inclusion criteria
* Male and female COPD patients aged =40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure.
* Current or ex-smokers who have a smoking history of at least 10 pack years.
* Patients who have been treated with a triple combination of LABA/LAMA/ICS for the last 3 months prior to screening.
* Patients featuring chronic bronchitis
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization, or a respiratory tract infection in the 4 weeks prior to screening, or between screening and randomization.
* Patients with any documented history of asthma, or with an onset of chronic respiratory symptoms, including a COPD diagnosis, prior to age 40 years.
* Patients with a body mass index (BMI) of more than 40 kg/m2.
* Use of other investigational drugs (approved or unapproved) within 30 days or 5 half-lives prior to screening, or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations.
* Pregnant or nursing (lactating) women, and women of childbearing potential not willing to use acceptable effective methods of contraception during study participation.

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 administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
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
12/09/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2022
Sample size
Target
Accrual to date
Final
974
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - South Brisbane
Recruitment hospital [2] 0 0
Novartis Investigative Site - Clayton
Recruitment hospital [3] 0 0
Novartis Investigative Site - Footscray
Recruitment hospital [4] 0 0
Novartis Investigative Site - Spearwood
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3011 - Footscray
Recruitment postcode(s) [4] 0 0
6163 - Spearwood
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
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
Nebraska
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
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Ohio
Country [12] 0 0
United States of America
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Oregon
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United States of America
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Texas
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United States of America
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Virginia
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Argentina
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Buenos Aires
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Argentina
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Entre Ríos
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Argentina
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Santa Fe
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Argentina
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Ciudad Autonoma de Bs As
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Argentina
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Mendoza
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Argentina
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Salta
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Austria
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Feldbach
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Austria
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Grieskirchen
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Austria
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Thalheim bei Wels
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Belgium
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Erpent
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Belgium
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Leuven
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Belgium
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Liege
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Czech Republic
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Czechia
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Varnsdorf
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Denmark
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Aalborg
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Denmark
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Copenhagen
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Denmark
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Hvidovre
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France
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Herault
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France
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Lyon Cedex 04
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France
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Pessac Cedex
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France
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Reims
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Germany
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Berlin
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Germany
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Frankfurt
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Halle
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Hamburg
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Landsberg
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Germany
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Leipzig
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Germany
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Mainz
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Germany
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Marburg
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Mittweida
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Witten
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Greece
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Heraklion Crete
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GTM
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Mako
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Pecs
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Italy
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GE
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Italy
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SI
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Italy
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VR
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Japan
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Aichi
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Japan
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Fukuoka
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Japan
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Gifu
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Hokkaido
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Ibaraki
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Kanagawa
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Mie
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Miyagi
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Osaka
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Tokyo
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Yamagata
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Korea, Republic of
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Seocho Gu
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Korea, Republic of
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Daegu
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Korea, Republic of
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Incheon
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Netherlands
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Eindhoven
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Netherlands
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Harderwijk
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Philippines
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Batangas
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Philippines
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Iloilo
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Philippines
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Bulacan
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Philippines
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Iloilo City
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Philippines
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Manila
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Poland
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Grudziadz
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Poland
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Katowice
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Poland
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Zawadzkie
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Slovakia
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Slovak Republic
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Slovakia
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Poprad
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Slovakia
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Presov
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Slovakia
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Spisska Nova Ves
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Slovakia
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Vysne Hagy
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Spain
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Andalucia
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Spain
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Comunidad Valenciana
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Spain
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Girona
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Thailand
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Hat Yai
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Thailand
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THA
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Thailand
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Bangkok
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Turkey
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Adana
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Turkey
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Mersin
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United Kingdom
State/province [100] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT04072887