A Study to Investigate the Efficacy and Safety of GSK1605786A in the Treatment of Subjects With Moderately-to-Severely Active Crohn's Disease

NCT ID: NCT01277666

Last Updated: 2017-09-19

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

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

608 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-12-20

Study Completion Date

2013-07-11

Brief Summary

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This is a randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of two doses (500 mg once daily and 500 mg twice daily) of GSK1605786A as compared to placebo over 12 weeks in adult subjects with moderately-to-severely active Crohn's disease. Efficacy will be assessed by proportion of subjects achieving response, defined as a decrease in Crohn's Disease Activity Index (CDAI) score of at least 100 points (clinical response). Clinical remission (CDAI score less than 150 points) will be evaluated as a key secondary endpoint. Safety will be assessed by recording of adverse events, clinical laboratory parameters, vital signs and electrocardiogram (ECG). Population pharmacokinetics will evaluate the two doses of GSK1605786A. Health outcomes assessments will include changes in Inflammatory Bowel Disease Questionnaire (IBDQ), Short Form-36 version 2 (SF-36v2), EQ-5D and Work Productivity and Activity Impairment-CD (WPAI-CD) and receipt of disability.

Detailed Description

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This is a multi-centre, randomised, double-blind, placebo-controlled, parallel group study to evaluate the efficacy of two oral doses of GSK1605786A (500 mg once daily, 500 mg twice daily) as compared to placebo in the induction of clinical response over a 12-week treatment period in subjects with moderately-to-severely active Crohn's disease. Secondary objectives will include assessment of the safety and evaluation of the efficacy in induction of remission.

The study is planned to randomise approximately 600 subjects (200 subjects/group) with active Crohn's disease, diagnosed for at least 4 months with a documented history of disease in the small and/or large intestine, and characterised by a Crohn's Disease Activity Index (CDAI) score between 220 to and 450, inclusive. Subjects must have reported an inadequate response or intolerance to Crohn's disease treatment with corticosteroids or immunosuppressants. Inclusion of subjects who received prior treatment with a biologic anti-tumour necrosis factor (TNF) agent will be limited to approximately 50% of the study population. All subjects are required to have a diagnosis with identification of anatomic location of Crohn's disease, which has been established by visualisation of the gastrointestinal tract within 12 months of screening. Subjects who have not had a visualisation of the gastrointestinal tract within 12 months are required to undergo an endoscopic assessment during the screening period. Subjects will be required to have evidence of current active inflammation at the time of randomisation either by endoscopy or by inflammatory biomarkers \[elevated C-reactive protein (CRP) greater than the upper limit of normal (ULN) plus a positive faecal calprotectin test\]. Subjects who do not meet the requirements based on inflammatory biomarker test results will be required to qualify based on endoscopic assessment during screening. Subjects will be allowed to participate in the study while continuing on stable doses of agents typically used to treat Crohn's disease. Following the screening period, subjects will be randomised at baseline to receive blinded treatment with one of two doses of GSK1605786A (500 mg once daily or twice daily) or placebo for 12 weeks. Response and remission endpoints, using the CDAI, will be evaluated at Weeks 4, 8 and 12.

Conditions

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Crohn's Disease

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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Placebo

orally administered

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo capsules, administered orally for 12 weeks

GSK1605786A 500mg once daily

orally administered

Group Type EXPERIMENTAL

GSK1605786A

Intervention Type DRUG

500 mg once daily, administered orally for 12 weeks

GSK1605786A 500mg twice daily

orally administered

Group Type EXPERIMENTAL

GSK1605786A

Intervention Type DRUG

500 mg twice daily, administered orally for 12 weeks

Interventions

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GSK1605786A

500 mg twice daily, administered orally for 12 weeks

Intervention Type DRUG

GSK1605786A

500 mg once daily, administered orally for 12 weeks

Intervention Type DRUG

Placebo

Placebo capsules, administered orally for 12 weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male or female subjects aged 18 years or older
* Written informed consent
* Diagnosis of Crohn's disease for greater than 4 months duration with small bowel and/or colonic involvement
* Confirmation of Crohn's disease established by visualisation of the gastrointestinal tract within the 12 months prior to screening or by screening endoscopy at study entry
* History of inadequate response and/or intolerance/adverse event leading to discontinuation of either corticosteroids or immunosuppressants
* Moderately-to-severely active disease characterised by a CDAI score between 220 and 450, inclusive, at Baseline
* Confirmation of current active Crohn's disease by screening endoscopy or inflammatory biomarkers \[elevated C-reactive protein (greater than upper limit of normal) plus positive test for faecal calprotectin\] at Screening
* Stable doses of permitted concomitant medications or having previously received, but are not currently receiving, medications for Crohn's disease
* Demonstrated ability to comply with Crohn's disease symptom recording using the interactive voice response system
* Females of child-bearing potential must be sexually inactive or commit to consistent and correct use of a contraceptive method of birth control with a failure rate of less than 1% for the duration of this study

Exclusion Criteria

* If female: pregnant, has a positive pregnancy test or is breast-feeding
* Diagnosis of coeliac disease, follow a gluten-free diet to manage symptoms, or positive test for coeliac disease
* Diagnosis of ulcerative or indeterminate colitis
* Enterocutaneous, abdominal or pelvic fistulae with abscesses or fistulae likely to require surgery during the study period
* Bowel surgery, other than appendectomy, within 12 weeks prior to screen and/or has surgery planned or deemed likely for Crohn's disease during the study period
* Extensive colonic resection, subtotal or total colectomy
* Presence of ileostomies, colostomies or rectal pouches
* Known fixed symptomatic stenoses
* History of more than 3 small bowel resections or diagnosis of short bowel syndrome
* Chronic use of narcotics for chronic pain defined as daily use of one or more doses of narcotic containing medication
* Use of prohibited medications, including enteral feeding or elemental diet, within their specified time frames

1. Biologic use: Use of any biologic (tumour necrosis factor inhibitor or natalizumab) within 8 weeks prior to screening
2. Corticosteroid use: Use of parenteral glucocorticoids within 4 weeks prior to screening
3. Immunospressant use: Use of cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil within 4 weeks prior to screening
4. Intravenous antibiotic use: Use of intravenous antibiotics for Crohn's disease within 4 weeks prior to screening
5. Use of rectal treatment with 5-ASA or corticosteroid enemas/suppositories within 2 weeks prior to screening
6. Use of tube or enteral feeding, elemental diet, or parenteral alimentation within 2 weeks prior to screening
7. Leukocytapheresis or granulocytapheresis within 2 weeks prior to screening
* Positive immunoassay for Clostridium difficile
* Known human immunodeficiency virus (HIV) infection
* Known varicella, herpes zoster, or other severe viral infection within 6 weeks of screening
* Immunisation with a live vaccine within 4 weeks of screening, with the exception of influenza vaccine
* Active or latent tuberculosis infection
* Current sepsis or infections requiring intravenous antibiotic therapy for more than 2 weeks
* Evidence of hepatic dysfunction, viral hepatitis, or current or chronic history of liver disease including non-alcoholic steatohepatitis (NASH)
* Positive test for Hepatitis B or Hepatitis C antibody at screening
* Corrected QT interval of ECG (electrocardiogram) greater than or equal to 450 milliseconds
* Concurrent illness or disability that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study
* History or evidence of adenomatous colonic polyps that have not been removed
* History of evidence of colonic mucosal dysplasia
* Current evidence of, or has been treated for a malignancy within the past five years (other than localised basal cell, squamous cell skin cancer, cervical dysplasia, or any cancer in situ that has been resected)
* Any previous participation in a clinical study of GSK1605786A (formerly ChemoCentryx compound CCX282-B)
* Medical history of sensitivity to any of the components of GSK1605786A
* Use of any investigational product within 30 days prior to screening
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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Little Rock, Arizona, United States

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Tucson, Arizona, United States

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Anaheim, California, United States

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Los Angeles, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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Lakewood, Colorado, United States

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Littleton, Colorado, United States

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Hamden, Connecticut, United States

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Jacksonville, Florida, United States

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Jacksonville, Florida, United States

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Maitland, Florida, United States

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Port Orange, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Oak Lawn, Illinois, United States

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Indianapolis, Indiana, United States

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Lexington, Kentucky, United States

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Hammond, Louisiana, United States

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Monroe, Louisiana, United States

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Chevy Chase, Maryland, United States

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Towson, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Chesterfield, Michigan, United States

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Troy, Michigan, United States

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Rochester, Minnesota, United States

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Jackson, Mississippi, United States

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Tupelo, Mississippi, United States

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Lee's Summit, Missouri, United States

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Lebanon, New Hampshire, United States

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Egg Harbor City, New Jersey, United States

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Voorhees Township, New Jersey, United States

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Great Neck, New York, United States

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Chapel Hill, North Carolina, United States

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Durham, North Carolina, United States

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Raleigh, North Carolina, United States

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Columbus, Ohio, United States

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Tulsa, Oklahoma, United States

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Portland, Oregon, United States

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Germantown, Tennessee, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Houston, Texas, United States

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Pasadena, Texas, United States

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San Antonio, Texas, United States

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Seattle, Washington, United States

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Seattle, Washington, United States

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Bankstown, New South Wales, Australia

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Hersten, Queensland, Australia

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Adelaide, South Australia, Australia

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Kurralta Park, South Australia, Australia

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Fitzroy, Victoria, Australia

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Prahran, Victoria, Australia

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Fremantle, Western Australia, Australia

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Hall in Tirol, , Austria

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Linz, , Austria

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Vienna, , Austria

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Vienna, , Austria

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Bonheiden, , Belgium

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Brussels, , Belgium

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Brussels, , Belgium

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Edegem, , Belgium

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Ghent, , Belgium

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Kortrijk, , Belgium

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Leuven, , Belgium

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Roeselare, , Belgium

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Abbotsford, British Columbia, Canada

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Vancouver, British Columbia, Canada

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Victoria, British Columbia, Canada

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Winnipeg, Manitoba, Canada

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Halifax, Nova Scotia, Canada

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Hamilton, Ontario, Canada

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Hamilton, Ontario, Canada

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Kingston, Ontario, Canada

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London, Ontario, Canada

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London, Ontario, Canada

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Ottawa, Ontario, Canada

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Richmond Hill, Ontario, Canada

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Toronto, Ontario, Canada

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Lévis, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Québec, Quebec, Canada

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Brno, , Czechia

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Hradec Králové, , Czechia

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Olomouc, , Czechia

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Ostrava - Vitkovice, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Aalborg, , Denmark

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Aarhus, , Denmark

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Herlev, , Denmark

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Hvidovre, , Denmark

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Odense, , Denmark

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Amiens, , France

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Clichy, , France

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Lille, , France

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Nantes, , France

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Nice, , France

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Paris, , France

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Pessac, , France

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Saint-Priest-en-Jarez, , France

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Vandœuvre-lès-Nancy, , France

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Freiburg im Breisgau, Baden-Wurttemberg, Germany

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Ulm, Baden-Wurttemberg, Germany

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Frankfurt am Main, Hesse, Germany

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Braunschweig, Lower Saxony, Germany

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Brinkum/Stuhr, Lower Saxony, Germany

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Hanover, Lower Saxony, Germany

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Cologne, North Rhine-Westphalia, Germany

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Minden, North Rhine-Westphalia, Germany

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Münster, North Rhine-Westphalia, Germany

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Münster, North Rhine-Westphalia, Germany

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Ludwigshafen am Rhein, Rhineland-Palatinate, Germany

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Dessau, Saxony-Anhalt, Germany

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Halle, Saxony-Anhalt, Germany

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Jena, Thuringia, Germany

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Berlin, , Germany

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Berlin, , Germany

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Berlin, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Békéscsaba, , Hungary

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Budapest, , Hungary

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Szekszárd, , Hungary

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Haifa, , Israel

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Holon, , Israel

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Jerusalem, , Israel

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Petah Tikva, , Israel

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Tel Aviv, , Israel

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Palermo, Sicily, Italy

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Genova, , Italy

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Modena, , Italy

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Roma, , Italy

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Roma, , Italy

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Aichi, , Japan

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Aichi, , Japan

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Chiba, , Japan

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Fukuoka, , Japan

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Fukuoka, , Japan

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Hokkaido, , Japan

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Hyōgo, , Japan

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Kagoshima, , Japan

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Kagoshima, , Japan

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Miyagi, , Japan

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Osaka, , Japan

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Osaka, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Almere Stad, , Netherlands

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Amsterdam, , Netherlands

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Amsterdam, , Netherlands

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Ede, , Netherlands

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Heerlen, , Netherlands

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Rotterdam, , Netherlands

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Auckland, , New Zealand

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Dunedin, , New Zealand

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Hamilton, , New Zealand

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Lower Hutt, , New Zealand

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Otahuhu, , New Zealand

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Tauranga, , New Zealand

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Ålesund, , Norway

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Bodø, , Norway

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Oslo, , Norway

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Tromsø, , Norway

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Trondheim, , Norway

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Tønsberg, , Norway

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Bydgoszcz, , Poland

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Bydgoszcz, , Poland

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Elblag, , Poland

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Lublin, , Poland

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Sopot, , Poland

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Torun, , Poland

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Wroclaw, , Poland

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Bratislava, , Slovakia

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Bratislava, , Slovakia

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Bratislava, , Slovakia

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Nitra, , Slovakia

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Nové Mesto nad Váhom, , Slovakia

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Prešov, , Slovakia

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Trnava, , Slovakia

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Bellville, , South Africa

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Claremont, , South Africa

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Observatory, , South Africa

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Parktown, , South Africa

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Daegu, , South Korea

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Pusan, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Wŏnju, , South Korea

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Badalona, , Spain

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Elche, , Spain

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Galdakao/Vizcaya, , Spain

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Madrid, , Spain

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Sabadell (Barcelona), , Spain

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Gothenburg, , Sweden

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Lund, , Sweden

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Stockholm, , Sweden

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Stockholm, , Sweden

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Umeå, , Sweden

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Harrow, Middlesex, United Kingdom

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Birmingham, , United Kingdom

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Bristol, , United Kingdom

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Edinburgh, , United Kingdom

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Manchester, , United Kingdom

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Newcastle upon Tyne, , United Kingdom

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Nottingham, , United Kingdom

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Oxford, , United Kingdom

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Salford, , United Kingdom

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Countries

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United States Australia Austria Belgium Canada Czechia Denmark France Germany Hungary Israel Italy Japan Netherlands New Zealand Norway Poland Slovakia South Africa South Korea Spain Sweden United Kingdom

Other Identifiers

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114151

Identifier Type: -

Identifier Source: org_study_id