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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01774786




Registration number
NCT01774786
Ethics application status
Date submitted
21/01/2013
Date registered
24/01/2013
Date last updated
30/12/2020

Titles & IDs
Public title
A Study of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Gastroesophageal Junction or Gastric Cancer
Scientific title
A Double-Blind, Placebo-Controlled, Randomized, Multicenter Phase III Study Evaluating the Efficacy and Safety of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Patients With HER2-Positive Metastatic Gastroesophageal Junction and Gastric Cancer
Secondary ID [1] 0 0
2012-003554-83
Secondary ID [2] 0 0
BO25114
Universal Trial Number (UTN)
Trial acronym
JACOB
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastric Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 5-Fluorouracil
Treatment: Drugs - Capecitabine
Treatment: Drugs - Cisplatin
Treatment: Drugs - Pertuzumab
Treatment: Drugs - Placebo
Treatment: Drugs - Trastuzumab

Experimental: Pertuzumab + Trastuzumab + Chemotherapy - Participants will receive pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine \[capecitabine or 5-fluorouracil\]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Placebo comparator: Placebo + Trastuzumab + Chemotherapy - Participants will receive placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine \[capecitabine or 5-fluorouracil\]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.


Treatment: Drugs: 5-Fluorouracil
Participants will receive 5-fluorouracil 800 milligrams per meter square (mg/m\^2)/24 hour IV infusion for 120 hours (Days 1-5) q3w for 6 cycles.

Treatment: Drugs: Capecitabine
Participants will receive capecitabine 1000 mg/m\^2 orally twice daily, evening of Day 1 to morning of Day 15 (28 doses) q3w for 6 cycles.

Treatment: Drugs: Cisplatin
Participants will receive cisplatin 80 mg/m\^2 IV q3w for 6 cycles.

Treatment: Drugs: Pertuzumab
Participants will receive pertuzumab 840 mg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Treatment: Drugs: Placebo
Participants will receive placebo (matched to pertuzumab) IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Treatment: Drugs: Trastuzumab
Participants will receive 8 mg/kg IV initial dose on Day 1, followed by 6 mg/kg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
From Baseline until death from any cause (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.4 [0-42] months vs. 25.0 [0-41] months; Final Analysis: 46.1 [0-70] months vs. 44.4 [0-68] months)
Secondary outcome [1] 0 0
Progression-Free Survival, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria
Timepoint [1] 0 0
Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months)
Secondary outcome [2] 0 0
Primary Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria
Timepoint [2] 0 0
Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months)
Secondary outcome [3] 0 0
Final Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria
Timepoint [3] 0 0
Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Final Analysis: 50.4 [0-70] months vs. 47.4 [0-66] months)
Secondary outcome [4] 0 0
Duration of Objective Response, as Determined by Investigator According to RECIST v1.1 Criteria
Timepoint [4] 0 0
Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months)
Secondary outcome [5] 0 0
Percentage of Participants With Clinical Benefit, as Determined by the Investigator According to RECIST v1.1 Criteria
Timepoint [5] 0 0
Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months)
Secondary outcome [6] 0 0
Overview of Safety: Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03
Timepoint [6] 0 0
From Baseline until end of post-treatment follow-up (up to 70 months)
Secondary outcome [7] 0 0
Number of Participants With Symptomatic or Asymptomatic Left Ventricular Systolic Dysfunction (LVSD)
Timepoint [7] 0 0
From Baseline until end of post-treatment follow-up (up to 70 months)
Secondary outcome [8] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score
Timepoint [8] 0 0
Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years)
Secondary outcome [9] 0 0
Change From Baseline in EORTC QLQ-Gastric Cancer Module (EORTC QLQ-STO22) Score
Timepoint [9] 0 0
Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years)
Secondary outcome [10] 0 0
Maximum Serum Concentration (Cmax) of Pertuzumab
Timepoint [10] 0 0
Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days)
Secondary outcome [11] 0 0
Cmax of Trastuzumab
Timepoint [11] 0 0
Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days)
Secondary outcome [12] 0 0
Minimum Serum Concentration (Cmin) of Pertuzumab
Timepoint [12] 0 0
Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)
Secondary outcome [13] 0 0
Cmin of Trastuzumab
Timepoint [13] 0 0
Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)

Eligibility
Key inclusion criteria
* Histologically confirmed metastatic adenocarcinoma of the stomach or GEJ
* Measurable or evaluable non-measurable disease as assessed by the investigator according to RECIST v1.1 criteria
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Life expectancy greater than equal to (>/=) 3 months
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Previous cytotoxic chemotherapy for advanced (metastatic) disease
* Evidence of disease progression documented within 6 months after completion of prior neoadjuvant or adjuvant cytotoxic chemotherapy, or both, or radiotherapy for GEJ adenocarcinoma
* Previous treatment with any HER2-directed therapy, at any time, for any duration
* Previous exposure to any investigational treatment within 30 days before the first dose of study treatment
* Radiotherapy within 30 days before the first dose of study treatment (within 2 weeks if given as palliation to bone metastases, if recovered from all toxicities)
* History or evidence of brain metastases
* Clinically significant active gastrointestinal (GI) bleeding (Grade >/=2 according to National Cancer Institute [NIC]-Common Terminology Criteria for Adverse Events Version 4.0 [CTCAEv.4.0])
* Residual toxicity resulting from previous therapy (for example, hematologic, cardiovascular, or neurologic toxicity that is Grade >/=2). Alopecia is permitted
* Other malignancy (in addition to gastric cancer [GC]) within 5 years before enrollment, except for carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin that has been previously treated with curative intent
* Inadequate hematologic, renal or liver function
* Pregnant or lactating women
* History of congestive heart failure of any New York Heart Association (NYHA) criteria
* Angina pectoris requiring treatment
* Myocardial infarction within the past 6 months before the first dose of study drug
* Clinically significant valvular heart disease or uncontrollable high-risk cardiac arrhythmia
* History or evidence of poorly controlled hypertension
* Baseline left ventricular ejection fraction (LVEF) value less than (<) 55 percent (%)
* Any significant uncontrolled intercurrent systemic illness
* Positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Royal Brisbane Womens Hosp; Division of Oncology - Herston
Recruitment hospital [2] 0 0
Monash Medical Centre; Oncology - Clayton
Recruitment hospital [3] 0 0
Austin Health; Cancer Clinical Trial Centre - Heidelberg
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital; Medical Oncology - Perth
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Nevada
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
South Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
Austria
State/province [9] 0 0
Salzburg
Country [10] 0 0
Austria
State/province [10] 0 0
Zams
Country [11] 0 0
Belgium
State/province [11] 0 0
Bruxelles
Country [12] 0 0
Brazil
State/province [12] 0 0
RJ
Country [13] 0 0
Brazil
State/province [13] 0 0
RS
Country [14] 0 0
Brazil
State/province [14] 0 0
SC
Country [15] 0 0
Brazil
State/province [15] 0 0
SP
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Plovdiv
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Sofia
Country [18] 0 0
Bulgaria
State/province [18] 0 0
Varna
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
China
State/province [21] 0 0
Beijing
Country [22] 0 0
China
State/province [22] 0 0
Changchun
Country [23] 0 0
China
State/province [23] 0 0
Changzhou
Country [24] 0 0
China
State/province [24] 0 0
ChongQing
Country [25] 0 0
China
State/province [25] 0 0
Fuzhou
Country [26] 0 0
China
State/province [26] 0 0
Guangzhou
Country [27] 0 0
China
State/province [27] 0 0
Hangzhou
Country [28] 0 0
China
State/province [28] 0 0
Harbin
Country [29] 0 0
China
State/province [29] 0 0
Nanchang
Country [30] 0 0
China
State/province [30] 0 0
Nanjing City
Country [31] 0 0
China
State/province [31] 0 0
Nantong
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China
State/province [32] 0 0
Shanghai
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China
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Shenyang
Country [34] 0 0
China
State/province [34] 0 0
Shijiazhuang
Country [35] 0 0
China
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Xi'an
Country [36] 0 0
China
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Xuzhou
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China
State/province [37] 0 0
Zhengzhou
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Croatia
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Zagreb
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El Salvador
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Salvador
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Finland
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Helsinki
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Finland
State/province [41] 0 0
Turku
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Germany
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Berlin
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Germany
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Essen
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Germany
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Esslingen
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Germany
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Hamburg
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Germany
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Leipzig
Country [47] 0 0
Germany
State/province [47] 0 0
Ludwigsburg
Country [48] 0 0
Germany
State/province [48] 0 0
Mainz
Country [49] 0 0
Germany
State/province [49] 0 0
Mannheim
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Germany
State/province [50] 0 0
Marburg
Country [51] 0 0
Germany
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Ulm
Country [52] 0 0
Guatemala
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Guatemala
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Hungary
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Budapest
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Hungary
State/province [54] 0 0
Debrecen
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Hungary
State/province [55] 0 0
Miskolc
Country [56] 0 0
Hungary
State/province [56] 0 0
Szeged
Country [57] 0 0
Italy
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Campania
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Italy
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Emilia-Romagna
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Italy
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Friuli-Venezia Giulia
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Italy
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Lazio
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Italy
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Lombardia
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Italy
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Marche
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Italy
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Puglia
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Italy
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Toscana
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Aichi
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Chiba
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Japan
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Ehime
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Japan
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Fukuoka
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Japan
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Gifu
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Japan
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Hiroshima
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Japan
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Hyogo
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Japan
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Kanagawa
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Japan
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Osaka
Country [74] 0 0
Japan
State/province [74] 0 0
Saitama
Country [75] 0 0
Japan
State/province [75] 0 0
Tokyo
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Japan
State/province [76] 0 0
Toyama
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Kazakhstan
State/province [77] 0 0
Almaty
Country [78] 0 0
Korea, Republic of
State/province [78] 0 0
Daegu
Country [79] 0 0
Korea, Republic of
State/province [79] 0 0
Seoul
Country [80] 0 0
Malaysia
State/province [80] 0 0
Kelantan
Country [81] 0 0
Malaysia
State/province [81] 0 0
Kuala Lumpur
Country [82] 0 0
Malaysia
State/province [82] 0 0
Sabah
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Mexico
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Mexico CITY (federal District)
Country [84] 0 0
Mexico
State/province [84] 0 0
Mexico City
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Mexico
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Oaxaca
Country [86] 0 0
Netherlands
State/province [86] 0 0
Amsterdam
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North Macedonia
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Bitola
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North Macedonia
State/province [88] 0 0
Skopje
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Panama
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Panama
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Peru
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Arequipa
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Peru
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Callao
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Peru
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Jesus Maria
Country [93] 0 0
Peru
State/province [93] 0 0
Lima
Country [94] 0 0
Poland
State/province [94] 0 0
Bialystok
Country [95] 0 0
Poland
State/province [95] 0 0
Brzozów
Country [96] 0 0
Poland
State/province [96] 0 0
Bydgoszcz
Country [97] 0 0
Poland
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Kraków
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Poland
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Opole
Country [99] 0 0
Poland
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Poznan
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Poland
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Rybnik
Country [101] 0 0
Poland
State/province [101] 0 0
Warszawa
Country [102] 0 0
Romania
State/province [102] 0 0
Cluj-Napoca
Country [103] 0 0
Romania
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Craiova
Country [104] 0 0
Romania
State/province [104] 0 0
Iasi
Country [105] 0 0
Russian Federation
State/province [105] 0 0
Kazan
Country [106] 0 0
Russian Federation
State/province [106] 0 0
Omsk
Country [107] 0 0
Russian Federation
State/province [107] 0 0
Ryazan
Country [108] 0 0
Russian Federation
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Samara
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Spain
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Alicante
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Spain
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Barcelona
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Spain
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Cordoba
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Spain
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Madrid
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Switzerland
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Lausanne
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Switzerland
State/province [114] 0 0
Luzern
Country [115] 0 0
Taiwan
State/province [115] 0 0
Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei City
Country [118] 0 0
Taiwan
State/province [118] 0 0
Taipei
Country [119] 0 0
Taiwan
State/province [119] 0 0
Taoyuan
Country [120] 0 0
Thailand
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Bangkok
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Thailand
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Khonkaen
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Thailand
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Songkhla
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Turkey
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Ankara
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Turkey
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Antalya
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Turkey
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Edirne
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Turkey
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Erzurum
Country [127] 0 0
Turkey
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Istanbul
Country [128] 0 0
Turkey
State/province [128] 0 0
Konya
Country [129] 0 0
Turkey
State/province [129] 0 0
Malatya

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.