An Evaluation of Sarilumab Plus Methotrexate Compared to Etanercept Plus Methotrexate in RA Patients Not Responding to Adalimumab Plus Methotrexate

NCT ID: NCT01764997

Last Updated: 2017-07-27

Study Results

Results available

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

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

776 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-30

Study Completion Date

2015-01-31

Brief Summary

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Primary Objective:

To demonstrate the treatment effect of sarilumab and methotrexate (MTX) compared to etanercept and MTX in participants with rheumatoid arthritis (RA) and an inadequate response to adalimumab and MTX by evaluation of the Disease Activity Score for 28 joints (DAS28).

Secondary Objectives:

To assess the signs and symptoms of RA in participants taking sarilumab in combination with MTX.

To assess the quality of life of participants with RA taking sarilumab in combination with MTX.

To assess the safety and tolerability of sarilumab in combination with MTX in participants with RA.

Detailed Description

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The maximum study duration per participant enrolled in the open label run-in phase and was eligible to enroll in the randomized phase of main study was 54 weeks:

* open label screening period of up to 4 weeks
* open-label treatment period of 16 weeks
* randomized screening period of 2 to 4 weeks
* randomized treatment post-treatment safety follow-up period of 6 weeks.

The maximum study duration per participant enrolled only in the open label run-in phase and was not eligible to enroll in the randomized phase of main study was 26 weeks:

* open label screening period of up to 4 weeks
* open-label treatment period of 16 weeks
* open label treatment post-treatment safety follow-up period of 6 weeks.

The maximum study duration per participant enrolled in the open label run-in phase and was eligible to enroll in the sarilumab sub-study was 82 weeks:

* open label screening period of up to 4 weeks
* open-label treatment period of 16 weeks
* screening period of 2 to 4 weeks
* sarilumab treatment period of 52 weeks
* sub-study post-treatment safety follow-up period of 6 weeks.

Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Adalimumab Open Label run-in

Adalimumab 40 mg every 2 weeks (Q2W) for 16 weeks added to stable dose of MTX.

Group Type EXPERIMENTAL

Methotrexate

Intervention Type DRUG

Dispensed according to local practice.

Adalimumab

Intervention Type DRUG

Pharmaceutical form: Solution for injection in pre-filled syringe; Route of administration: Subcutaneous

Etanercept + MTX (Randomized)

Etanercept 50 mg in combination with Placebo for sarilumab Q2W and etanercept 50 mg on alternating weeks for 24 weeks added to stable dose of MTX.

Group Type ACTIVE_COMPARATOR

Etanercept

Intervention Type DRUG

Pharmaceutical form: Solution for injection in pre-filled syringe; Route of administration: Subcutaneous

Methotrexate

Intervention Type DRUG

Dispensed according to local practice.

Placebo (for sarilumab)

Intervention Type DRUG

Sarilumab 150 mg + MTX (Randomized)

Sarilumab 150 mg in combination with placebo for etanercept Q2W and placebo for etanercept on alternating weeks for 24 weeks added to stable dose of MTX.

Group Type EXPERIMENTAL

Sarilumab

Intervention Type DRUG

Pharmaceutical form: Solution for injection in pre-filled syringe; Route of administration: Subcutaneous

Methotrexate

Intervention Type DRUG

Dispensed according to local practice.

Placebo (for etanercept)

Intervention Type DRUG

Sarilumab 200 mg + MTX (Randomized)

Sarilumab 200 mg in combination with placebo for etanercept Q2W and placebo for etanercept on alternating weeks for 24 weeks added to stable dose of MTX.

Group Type EXPERIMENTAL

Sarilumab

Intervention Type DRUG

Pharmaceutical form: Solution for injection in pre-filled syringe; Route of administration: Subcutaneous

Methotrexate

Intervention Type DRUG

Dispensed according to local practice.

Placebo (for etanercept)

Intervention Type DRUG

Sarilumab 150 mg + MTX Open Label Sub-study

Sarilumab 150 mg Q2W for 52 weeks added to stable dose of MTX.

Group Type EXPERIMENTAL

Sarilumab

Intervention Type DRUG

Pharmaceutical form: Solution for injection in pre-filled syringe; Route of administration: Subcutaneous

Methotrexate

Intervention Type DRUG

Dispensed according to local practice.

Interventions

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Sarilumab

Pharmaceutical form: Solution for injection in pre-filled syringe; Route of administration: Subcutaneous

Intervention Type DRUG

Etanercept

Pharmaceutical form: Solution for injection in pre-filled syringe; Route of administration: Subcutaneous

Intervention Type DRUG

Methotrexate

Dispensed according to local practice.

Intervention Type DRUG

Placebo (for sarilumab)

Intervention Type DRUG

Placebo (for etanercept)

Intervention Type DRUG

Adalimumab

Pharmaceutical form: Solution for injection in pre-filled syringe; Route of administration: Subcutaneous

Intervention Type DRUG

Other Intervention Names

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SAR153191 REGN88 Enbrel

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of RA \>/= 3 months duration.
* Continuous treatment of MTX 10 - 25 mg/week (or per local labeling requirements if the dose range differs) for at least 12 weeks before screening visit and on a stable dose for 8 weeks before screening visit.
* Active disease defined as: at least 6/66 swollen and 8/68 tender joints and high sensitivity C-reactive protein \> 10 mg/L.

Exclusion Criteria

* Age \< 18 years.
* Use of parenteral corticosteroids or intra-articular corticosteroids within 4 weeks of the screening visit.
* Use of oral corticosteroids in a dose higher than prednisone 10 mg or equivalent per day, or a change in dosage within 4 weeks of the screening visit.
* Prior treatment with a tumor necrosis factor (TNF)-alpha inhibitor, or other biological disease modifying anti-rheumatoid drug (DMARD) or Janus Kinase inhibitor.
* New treatment with or dose-adjustment of on-going nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclo-oxygenase-2 (COX-2) inhibitors within 4 weeks of the screening visit.
* Treatment with traditional oral DMARD /immunosuppressive agents other than MTX within 4 weeks or 12 weeks before the screening visit, depending on DMARD.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Investigational Site Number 840004

Birmingham, Alabama, United States

Site Status

Investigational Site Number 840212

Glendale, California, United States

Site Status

Investigational Site Number 840211

Thousand Oaks, California, United States

Site Status

Investigational Site Number 840049

Upland, California, United States

Site Status

Investigational Site Number 840205

Victorville, California, United States

Site Status

Investigational Site Number 840201

Denver, Colorado, United States

Site Status

Investigational Site Number 840209

Danbury, Connecticut, United States

Site Status

Investigational Site Number 840203

Washington D.C., District of Columbia, United States

Site Status

Investigational Site Number 840210

Clearwater, Florida, United States

Site Status

Investigational Site Number 840128

Ormond Beach, Florida, United States

Site Status

Investigational Site Number 840063

Palm Harbor, Florida, United States

Site Status

Investigational Site Number 840060

Sarasota, Florida, United States

Site Status

Investigational Site Number 840207

Tampa, Florida, United States

Site Status

Investigational Site Number 840018

Idaho Falls, Idaho, United States

Site Status

Investigational Site Number 840213

Indianapolis, Indiana, United States

Site Status

Investigational Site Number 840109

Lake Charles, Louisiana, United States

Site Status

Investigational Site Number 840073

Cumberland, Maryland, United States

Site Status

Investigational Site Number 840202

Hagerstown, Maryland, United States

Site Status

Investigational Site Number 840204

Battle Creek, Michigan, United States

Site Status

Investigational Site Number 840150

Lansing, Michigan, United States

Site Status

Investigational Site Number 840200

Jackson, Mississippi, United States

Site Status

Investigational Site Number 840037

Tupelo, Mississippi, United States

Site Status

Investigational Site Number 840112

Lincoln, Nebraska, United States

Site Status

Investigational Site Number 840056

New York, New York, United States

Site Status

Investigational Site Number 840117

Pittsburgh, Pennsylvania, United States

Site Status

Investigational Site Number 840016

North Charleston, South Carolina, United States

Site Status

Investigational Site Number 840025

Jackson, Tennessee, United States

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Investigational Site Number 840074

Mesquite, Texas, United States

Site Status

Investigational Site Number 840061

Tacoma, Washington, United States

Site Status

Investigational Site Number 840124

Clarksburg, West Virginia, United States

Site Status

Investigational Site Number 032052

Buenos Aires, , Argentina

Site Status

Investigational Site Number 032050

Buenos Aires, , Argentina

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Investigational Site Number 032053

La Plata, , Argentina

Site Status

Investigational Site Number 032013

Rosario, , Argentina

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Investigational Site Number 032005

San Miguel de Tucumán, , Argentina

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Investigational Site Number 032051

San Miguel de Tucumán, , Argentina

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Investigational Site Number 032009

Zárate, , Argentina

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Investigational Site Number 036020

Camperdown, , Australia

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Investigational Site Number 036004

Heidelberg West, , Australia

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Investigational Site Number 036014

Victoria Park, , Australia

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Investigational Site Number 036007

Woodville, , Australia

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Investigational Site Number 076001

Curitiba, , Brazil

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Investigational Site Number 076016

Curitiba, , Brazil

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Investigational Site Number 076006

Goiânia, , Brazil

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Investigational Site Number 076010

Juiz de Fora, , Brazil

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Investigational Site Number 076005

Rio de Janeiro, , Brazil

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Investigational Site Number 076013

Vitória, , Brazil

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Investigational Site Number 152005

Osorno, , Chile

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Investigational Site Number 152018

Santiago, , Chile

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Investigational Site Number 152001

Santiago, , Chile

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Investigational Site Number 152002

Santiago, , Chile

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Investigational Site Number 152011

Santiago, , Chile

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Investigational Site Number 152015

Temuco, , Chile

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Investigational Site Number 170016

Bogotá, , Colombia

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Investigational Site Number 170040

Bogotá, , Colombia

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Investigational Site Number 170001

Bogotá, , Colombia

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Investigational Site Number 170007

Bucaramanga, , Colombia

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Investigational Site Number 170009

Bucaramanga, , Colombia

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Investigational Site Number 170041

Medellín, , Colombia

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Investigational Site Number 203004

Ostrava, , Czechia

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Investigational Site Number 203032

Prague, , Czechia

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Investigational Site Number 203001

Prague, , Czechia

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Investigational Site Number 203031

Prague, , Czechia

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Investigational Site Number 203033

Prague, , Czechia

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Prague, , Czechia

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Investigational Site Number 203002

Uherské Hradiště, , Czechia

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Investigational Site Number 203006

Zlín, , Czechia

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Investigational Site Number 218003

Cuenca, , Ecuador

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Investigational Site Number 218001

Guayaquil, , Ecuador

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Investigational Site Number 218002

Quito, , Ecuador

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Investigational Site Number 246001

Helsinki, , Finland

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Investigational Site Number 246002

Hyvinkää, , Finland

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Investigational Site Number 246030

Oulu, , Finland

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Investigational Site Number 246003

Pori, , Finland

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Investigational Site Number 246032

Tampere, , Finland

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Investigational Site Number 250003

Amiens, , France

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Investigational Site Number 250007

Bobigny, , France

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Investigational Site Number 250001

La Roche-sur-Yon, , France

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Investigational Site Number 250002

Montpellier, , France

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Investigational Site Number 250005

Paris, , France

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Investigational Site Number 250004

Paris, , France

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Investigational Site Number 250006

Strasbourg, , France

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Toulouse, , France

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Investigational Site Number 276007

Berlin, , Germany

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Investigational Site Number 276057

Berlin, , Germany

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Investigational Site Number 276058

Cologne, , Germany

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Investigational Site Number 276056

Dresden, , Germany

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Investigational Site Number 276055

Dresden, , Germany

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Erlangen, , Germany

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Investigational Site Number 276013

Hamburg, , Germany

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Herne, , Germany

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Ludwigsfelde, , Germany

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Rostock, , Germany

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Athens, , Greece

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Heraklion, , Greece

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N. Efkarpia, , Greece

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Pátrai, , Greece

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Budapest, , Hungary

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Debrecen, , Hungary

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Esztergom, , Hungary

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Gy?r, , Hungary

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Gyula, , Hungary

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Ashkelon, , Israel

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Haifa, , Israel

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Haifa, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Investigational Site Number 376034

Tel Litwinsky, , Israel

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Florence, , Italy

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Investigational Site Number 380004

Genova, , Italy

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Investigational Site Number 380005

Genova, , Italy

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Investigational Site Number 380041

L’Aquila, , Italy

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Investigational Site Number 380042

Valeggio sul Mincio, , Italy

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Investigational Site Number 428002

Liepāja, , Latvia

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Investigational Site Number 428001

Riga, , Latvia

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Investigational Site Number 428003

Ventspils, , Latvia

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Investigational Site Number 440005

Kaunas, , Lithuania

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Klaipėda, , Lithuania

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Investigational Site Number 440010

Panevezys, , Lithuania

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Investigational Site Number 440011

Vilnius, , Lithuania

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Investigational Site Number 458012

Batu Caves, , Malaysia

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George Town, , Malaysia

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Investigational Site Number 458001

Ipoh, , Malaysia

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Investigational Site Number 458013

Kota Bharu, , Malaysia

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Investigational Site Number 458002

Kuching, , Malaysia

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Investigational Site Number 458010

Malacca, , Malaysia

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Investigational Site Number 458011

Seremban, , Malaysia

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Investigational Site Number 484023

Chihuahua City, , Mexico

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Investigational Site Number 484027

Ciudad Obregón, , Mexico

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Investigational Site Number 484029

Deleg. Benito Juárez, , Mexico

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Investigational Site Number 484013

Guadalajara, , Mexico

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Investigational Site Number 484018

Guadalajara, , Mexico

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Investigational Site Number 484010

Mexicali, , Mexico

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Investigational Site Number 484026

Mexicali, , Mexico

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Investigational Site Number 484052

Mexico City, , Mexico

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Investigational Site Number 484004

Mérida, , Mexico

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Investigational Site Number 484017

México, , Mexico

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Investigational Site Number 484025

San Luis, , Mexico

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Tijuana, , Mexico

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Investigational Site Number 554007

Auckland, , New Zealand

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Dunedin, , New Zealand

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Hamilton, , New Zealand

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Nelson, , New Zealand

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Investigational Site Number 604020

Lima, , Peru

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Investigational Site Number 616019

Bydgoszcz, , Poland

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Investigational Site Number 616054

Bytom, , Poland

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Investigational Site Number 616052

Działdowo, , Poland

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Investigational Site Number 616015

Elblag, , Poland

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Investigational Site Number 616057

Krakow, , Poland

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Investigational Site Number 616059

Krakow, , Poland

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Investigational Site Number 616061

Krakow, , Poland

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Investigational Site Number 616005

Lublin, , Poland

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Investigational Site Number 616063

Myślenice, , Poland

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Investigational Site Number 616018

Poznan, , Poland

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Investigational Site Number 616013

Sosnowiec, , Poland

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Investigational Site Number 616056

Starachowice, , Poland

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Investigational Site Number 616016

Szczecin, , Poland

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Investigational Site Number 616058

Ustroń, , Poland

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Investigational Site Number 616051

Warsaw, , Poland

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Investigational Site Number 616053

Żyrardów, , Poland

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Investigational Site Number 642041

Bacau, , Romania

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Investigational Site Number 642001

Bucharest, , Romania

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Investigational Site Number 642040

Bucharest, , Romania

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Investigational Site Number 642002

Bucharest, , Romania

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Investigational Site Number 642012

Bucharest, , Romania

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Investigational Site Number 642004

Bucharest, , Romania

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Investigational Site Number 642023

Bucharest, , Romania

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Investigational Site Number 642042

Bucharest, , Romania

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Investigational Site Number 642005

Galati, , Romania

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Investigational Site Number 642013

Iași, , Romania

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Investigational Site Number 642014

Iași, , Romania

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Investigational Site Number 642022

Târgovişte, , Romania

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Investigational Site Number 643006

Kemerovo, , Russia

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Investigational Site Number 643056

Krasnoyarsk, , Russia

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Investigational Site Number 643052

Moscow, , Russia

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Investigational Site Number 643021

Moscow, , Russia

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Investigational Site Number 643031

Moscow, , Russia

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Investigational Site Number 643030

Moscow, , Russia

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Investigational Site Number 643022

Novosibirsk, , Russia

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Investigational Site Number 643058

Saint Peterburg, , Russia

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Investigational Site Number 643008

Saint Petersburg, , Russia

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Investigational Site Number 643010

Samara, , Russia

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Investigational Site Number 643011

Saratov, , Russia

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Investigational Site Number 643059

Smolensk, , Russia

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Investigational Site Number 643013

Ufa, , Russia

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Investigational Site Number 643050

Voronezh, , Russia

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Investigational Site Number 643057

Yaroslavl, , Russia

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Investigational Site Number 643051

Yaroslavl, , Russia

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Investigational Site Number 710011

Cape Town, , South Africa

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Investigational Site Number 710007

Cape Town, , South Africa

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Investigational Site Number 710008

Pretoria, , South Africa

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Investigational Site Number 710006

Pretoria, , South Africa

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Investigational Site Number 710010

Stellenbsoch, , South Africa

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Investigational Site Number 410020

Busan, , South Korea

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Investigational Site Number 410006

Busan, , South Korea

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Investigational Site Number 410013

Daegu, , South Korea

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Investigational Site Number 410005

Daejeon, , South Korea

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Investigational Site Number 410011

Jeonju, , South Korea

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Investigational Site Number 410016

Seoul, , South Korea

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Investigational Site Number 410015

Seoul, , South Korea

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Investigational Site Number 410022

Seoul, , South Korea

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Investigational Site Number 410023

Seoul, , South Korea

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Investigational Site Number 410021

Seoul, , South Korea

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Investigational Site Number 410008

Suwon, , South Korea

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Investigational Site Number 724009

A Coruña, , Spain

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Investigational Site Number 724043

Córdoba, , Spain

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Investigational Site Number 724042

Madrid, , Spain

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Investigational Site Number 724041

Madrid, , Spain

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Investigational Site Number 724040

Madrid, , Spain

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Investigational Site Number 724001

Málaga, , Spain

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Investigational Site Number 724011

Sabadell, , Spain

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Investigational Site Number 724012

Santiago de Compostela, , Spain

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Investigational Site Number 158010

Changhua, , Taiwan

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Investigational Site Number 158004

Chiayi City, , Taiwan

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Investigational Site Number 158012

Kaohsiung City, , Taiwan

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Investigational Site Number 158011

Kaohsiung City, , Taiwan

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Investigational Site Number 158006

Taipei, , Taiwan

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Investigational Site Number 764002

Bangkok, , Thailand

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Investigational Site Number 764010

Bangkok, , Thailand

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Investigational Site Number 764003

Bangkok Noi, , Thailand

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Investigational Site Number 764011

Khon Kaen, , Thailand

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Investigational Site Number 804003

Dnipropetrovsk, , Ukraine

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Investigational Site Number 804002

Donetsk, , Ukraine

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Investigational Site Number 804024

Donetsk, , Ukraine

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Investigational Site Number 804029

Ivano-Frankivsk, , Ukraine

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Investigational Site Number 804010

Kharkiv, , Ukraine

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Investigational Site Number 804001

Kharkiv, , Ukraine

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Investigational Site Number 804025

Kiev, , Ukraine

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Investigational Site Number 804023

Kyiv, , Ukraine

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Investigational Site Number 804014

Kyiv, , Ukraine

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Investigational Site Number 804027

Kyiv, , Ukraine

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Investigational Site Number 804011

Kyiv, , Ukraine

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Investigational Site Number 804030

Lutsk, , Ukraine

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Investigational Site Number 804005

Lviv, , Ukraine

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Investigational Site Number 804033

Lviv, , Ukraine

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Investigational Site Number 804020

Lviv, , Ukraine

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Investigational Site Number 804032

Odesa, , Ukraine

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Investigational Site Number 804022

Odesa, , Ukraine

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Investigational Site Number 804012

Odesa, , Ukraine

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Investigational Site Number 804021

Simferopol, , Ukraine

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Investigational Site Number 804028

Zaporizhzhya, , Ukraine

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Investigational Site Number 804031

Zhytomyr, , Ukraine

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Investigational Site Number 826023

Barnsley, , United Kingdom

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Investigational Site Number 826022

Birmingham, , United Kingdom

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Investigational Site Number 826021

Dudley, , United Kingdom

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Investigational Site Number 826026

Durham, , United Kingdom

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Investigational Site Number 826027

Durham, , United Kingdom

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Investigational Site Number 826020

Harlow, , United Kingdom

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Investigational Site Number 826025

Wigan, , United Kingdom

Site Status

Countries

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United States Argentina Australia Brazil Chile Colombia Czechia Ecuador Finland France Germany Greece Hungary Israel Italy Latvia Lithuania Malaysia Mexico New Zealand Peru Poland Romania Russia South Africa South Korea Spain Taiwan Thailand Ukraine United Kingdom

Other Identifiers

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2012-001984-66

Identifier Type: -

Identifier Source: secondary_id

U1111-1131-6653

Identifier Type: OTHER

Identifier Source: secondary_id

EFC11574

Identifier Type: -

Identifier Source: org_study_id

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