Clinical trial NCT00626548: A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) in Non-metastatic Hormone Resistant Prostate Cancer
Official title: A Phase III, Randomised, Placebo-controlled, Double-blind Study to Assess the Efficacy and Safety of Once-daily Orally Administered ZD4054 (Zibotentan) 10 mg in Non-metastatic Hormone-resistant Prostate Cancer Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Hormone Resistant Prostate Cancer
Endothelin A Receptor Antagonist
Endothelin A
Endothelin A antagonist
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2008-02-29
Enrollment: 2577
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Enthuse M0 is a large phase III clinical trial studying the efficacy of ZD4054 (Zibotentan) in hormone resistant prostate cancer (HRPC).

This clinical trial will test if the Endothelin A Receptor Antagonist ZD4054 (Zibotentan) can improve progression-free survival and overall survival against a background of existing prostate cancer treatments.

ZD4054 (Zibotentan) is a new type of agent, which is thought to slow tumour growth and spread by blocking Endothelin receptor activity. This trial will look at the effects of ZD4054 (Zibotentan) in hormone resistant prostate cancer (HRPC) patients who have had rising PSA after surgical or medical castration but have no evidence of metastases.

All patients participating in this clinical trial will receive existing prostate cancer treatments in addition to trial therapy.

Half the patients will receive ZD4054 (Zibotentan) , and half the patients will receive placebo in addition to standard prostate cancer therapy. By participating in this trial there is a 50% chance that patients will receive an agent that may slow the progression of the tumour.

No patients will be deprived of standard prostate cancer therapy.


Eligibility criteria: Inclusion Criteria:

Patients who answer TRUE to the following criteria may be eligible to participate in this study.

* Confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate) that has NOT spread to the other parts of the body (metastases). Patients with lymph node involvement may be eligible if specified criteria is met.
* Increasing Prostate Specific Antigen (PSA), collected within one year of enrollment
* Currently receiving treatment with surgical or medical castration

Exclusion Criteria:

Patients who answer TRUE to the following may NOT be eligible to participate in this study.

* Currently using opiate based pain killers for cancer related pain
* Previous treatment with chemotherapy (paclitaxel, docetaxel, and mitoxantrone). Prior targeted cancer therapies are permitted if received during a previous clinical trial
* Suffering from heart failure or had a myocardial infarction within last 6 months
* A history of epilepsy or seizures

Primary outcomes:
measure: Overall Survival
timeFrame: From date of randomization until date of death, assessed up to 33 months
measure: Progression Free Survival
timeFrame: Participants were followed up for progression every 4 weeks for the first 16 weeks then every 16 weeks
Secondary outcomes:
measure: Health Related Quality of Life
timeFrame: Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks
measure: Time to Prostate-specific Antigen (PSA) Progression
timeFrame: Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks
measure: Time to Symptomatic Progression
timeFrame: Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Greenbrae
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Denver
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state: Colorado
city: Norwich
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facility: Research Site
state: Connecticut
city: Washington
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state: District of Columbia
city: Boca Raton
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state: Florida
city: Miami
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state: Florida
city: Ocala
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state: Florida
city: Port St. Lucie
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state: Florida
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state: Georgia
city: Macon
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city: Rockville
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city: Minneapolis
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state: Minnesota
city: Lincoln
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state: Nebraska
city: Las Vegas
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state: Nevada
city: Brooklyn
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state: New York
city: Chapel Hill
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state: North Carolina
city: Bismarck
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state: North Dakota
city: Canton
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state: Ohio
city: Cincinnati
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city: Philadelphia
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state: Pennsylvania
city: Pittsburgh
country: United States
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state: Pennsylvania
city: Charleston
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state: South Carolina
city: Mystle Beach
country: United States
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state: South Carolina
city: Raleigh
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state: South Carolina
city: Memphis
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state: Tennessee
city: Nashville
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state: Tennessee
city: San Antonio
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state: Texas
city: Burlington
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state: Vermont
city: Seattle
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state: Washington
city: Wenatchee
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state: Washington
city: Milwaukee
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state: Wisconsin
city: Ciudad Autonoma de Buenos Aires
country: Argentina
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state: Buenos Aires
city: Rosario
country: Argentina
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state: Santa Fe
city: Santa Fe
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facility: Research Site
city: Darlinghurst
country: Australia
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state: New South Wales
city: Hornsby
country: Australia
facility: Research Site
state: New South Wales
city: Westmead
country: Australia
facility: Research Site
state: New South Wales
city: Wollongong
country: Australia
facility: Research Site
state: New South Wales
city: Wodonga
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facility: Research Site
state: Victoria
city: Nedlands
country: Australia
facility: Research Site
state: Western Australia
city: Sydney
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city: Graz
country: Austria
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city: Innsbruck
country: Austria
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city: Wels
country: Austria
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country: Belgium
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city: Brussels
country: Belgium
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city: Edegem
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city: Gent
country: Belgium
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state: Goias
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state: RJ
city: Santo Andre
country: Brazil
facility: Research Site
state: Sao Paulo
city: Sao Paulo
country: Brazil
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city: Calgary
country: Canada
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state: Alberta
city: Edmonton
country: Canada
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state: Alberta
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state: British Columbia
city: Victoria
country: Canada
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state: British Columbia
city: Winnipeg
country: Canada
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state: Manitoba
city: Burlington
country: Canada
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state: Ontario
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Kingston
country: Canada
facility: Research Site
state: Ontario
city: Kitchener
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: North York
country: Canada
facility: Research Site
state: Ontario
city: Oakville
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Greenfeild Park
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Point-Claire
country: Canada
facility: Research Site
state: Quebec
city: Quebec City
country: Canada
facility: Research Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Research Site
state: Quebec
city: La Serena
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Vina del Mar
country: Chile
facility: Research Site
city: Nanjing
country: China
facility: Research Site
state: Jiangsu
city: Hangzhou
country: China
facility: Research Site
state: Zhejiang
city: Beijing
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou City
country: China
facility: Research Site
city: Hubei
country: China
facility: Research Site
city: Jiangsu
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanxi
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Zejiang
country: China
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city: Bogota
country: Colombia
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city: Medellin
country: Colombia
facility: Research Site
city: Brno
country: Czech Republic
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country: Czech Republic
facility: Research Site
city: Jablonec nad Nisou
country: Czech Republic
facility: Research Site
city: Kromeriz
country: Czech Republic
facility: Research Site
city: Olomouc
country: Czech Republic
facility: Research Site
city: Prague 2
country: Czech Republic
facility: Research Site
city: Prague 4
country: Czech Republic
facility: Research Site
city: Prague 6
country: Czech Republic
facility: Research Site
city: Praha
country: Czech Republic
facility: Research Site
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country: Czech Republic
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country: Denmark
facility: Research Site
city: Frederiksberg
country: Denmark
facility: Research Site
city: Herlev
country: Denmark
facility: Research Site
city: Holstebro
country: Denmark
facility: Research Site
city: Kobenhavn
country: Denmark
facility: Research Site
city: Odense
country: Denmark
facility: Research Site
city: Roskilde
country: Denmark
facility: Research Site
city: Helsinki
country: Finland
facility: Research Site
city: Joensuu
country: Finland
facility: Research Site
city: Oulu
country: Finland
facility: Research Site
city: Seinajoki
country: Finland
facility: Research Site
city: Tampere
country: Finland
facility: Research Site
city: Caen cedex
country: France
facility: Research Site
city: Creteil
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Lyon cedex 03
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Orleans Cedex
country: France
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city: Paris
country: France
facility: Research Site
city: Pierre Benite cedex
country: France
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city: Poitiers Cedex
country: France
facility: Research Site
city: Reims cedex
country: France
facility: Research Site
city: Reims
country: France
facility: Research Site
city: Rennes cedex 9
country: France
facility: Research Site
city: Rouen
country: France
facility: Research Site
city: Suresnes
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Vandoeuvre-les-Nancy cedex
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Augsburg
country: Germany
facility: Research Site
city: Bad Ems
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bonn
country: Germany
facility: Research Site
city: Borken
country: Germany
facility: Research Site
city: Chemnitz
country: Germany
facility: Research Site
city: Emmendingen
country: Germany
facility: Research Site
city: Fuerth
country: Germany
facility: Research Site
city: Gelsenkirchen-Buer
country: Germany
facility: Research Site
city: Germering
country: Germany
facility: Research Site
city: Goettingen
country: Germany
facility: Research Site
city: Holzminden
country: Germany
facility: Research Site
city: Kirchheim/Teck
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Lubeck
country: Germany
facility: Research Site
city: Mannheim
country: Germany
facility: Research Site
city: Muehlacker
country: Germany
facility: Research Site
city: Muehlheim an der Ruhr
country: Germany
facility: Research Site
city: Muenchen-Planegg
country: Germany
facility: Research Site
city: Muenchen
country: Germany
facility: Research Site
city: Muenster
country: Germany
facility: Research Site
city: Reutlingen
country: Germany
facility: Research Site
city: Rostock
country: Germany
facility: Research Site
city: Tuebingen
country: Germany
facility: Research Site
city: Waltshut-Tiengen
country: Germany
facility: Research Site
city: Wuppertal
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Gyor
country: Hungary
facility: Research Site
city: Miskolc
country: Hungary
facility: Research Site
city: Nyiregyhaza
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Szekesfehervar
country: Hungary
facility: Research Site
city: Ahmedabad
country: India
facility: Research Site
state: Gujarat
city: Nadiad
country: India
facility: Research Site
state: Gujarat
city: Kochi
country: India
facility: Research Site
state: Kerala
city: Pune
country: India
facility: Research Site
state: Maharashtra
city: Chennai
country: India
facility: Research Site
state: Tamil Nadu, India
city: Lucknow
country: India
facility: Research Site
state: Uttar Pradesh
city: Kolkota
country: India
facility: Research Site
state: West Bengal
city: New Delhi
country: India
facility: Research Site
city: Dublin 7
country: Ireland
facility: Research Site
city: Dublin 8
country: Ireland
facility: Research Site
city: Dublin
country: Ireland
facility: Research Site
city: Be'er Sheva
country: Israel
facility: Research Site
city: Be'er-Ya'akov
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Holon
country: Israel
facility: Research Site
city: Jeruslaem
country: Israel
facility: Research Site
city: Petah-Tikva
country: Israel
facility: Research Site
city: Tel-HaShomer - Ramat Gan
country: Israel
facility: Research Site
city: Ancona
country: Italy
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Bergamo
country: Italy
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Como
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Messina
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Terni
country: Italy
facility: Research Site
city: Varese
country: Italy
facility: Research Site
city: Hirosaki-City
country: Japan
facility: Research Site
state: Aomori
city: Chiba-City
country: Japan
facility: Research Site
state: Chiba
city: Narashino-city
country: Japan
facility: Research Site
state: Chiba
city: Matsuyama-City
country: Japan
facility: Research Site
state: Ehime
city: Fukuoka-City
country: Japan
facility: Research Site
state: Fukuoka
city: Maebashi-City
country: Japan
facility: Research Site
state: Gunma
city: Otake-City
country: Japan
facility: Research Site
state: Hiroshima
city: Sapporo-City
country: Japan
facility: Research Site
state: Hokkaido
city: Kobe-City
country: Japan
facility: Research Site
state: Hyogo
city: Ibaraki-machi
country: Japan
facility: Research Site
state: Ibaraki
city: Mito-City
country: Japan
facility: Research Site
state: Ibaraki
city: Tsukuba-City
country: Japan
facility: Research Site
state: Ibaraki
city: Kita-gun
country: Japan
facility: Research Site
state: Kagawa
city: Sagamihara-City
country: Japan
facility: Research Site
state: Kanagawa
city: Kamigyo-ku
country: Japan
facility: Research Site
state: Kyoto
city: Kyoto-City
country: Japan
facility: Research Site
state: Kyoto
city: Sendai-City
country: Japan
facility: Research Site
state: Miyagi
city: Ueda-City
country: Japan
facility: Research Site
state: Nagano
city: Kashihara
country: Japan
facility: Research Site
state: Nara
city: Oita-City
country: Japan
facility: Research Site
state: Oita
city: Kurashiki
country: Japan
facility: Research Site
state: Okayama
city: Osaka-City
country: Japan
facility: Research Site
state: Osaka
city: Osaka-Sayama-City
country: Japan
facility: Research Site
state: Osaka
city: Suita-City
country: Japan
facility: Research Site
state: Osaka
city: Wako-City
country: Japan
facility: Research Site
state: Saitama
city: Hamamatsu-city
country: Japan
facility: Research Site
state: Shizuoka
city: Sunto-gun
country: Japan
facility: Research Site
state: Shizuoka
city: Bunkyo-ku
country: Japan
facility: Research Site
state: Tokyo
city: Fuchu_city
country: Japan
facility: Research Site
state: Tokyo
city: Itabashi-Ku
country: Japan
facility: Research Site
state: Tokyo
city: Meguro-ku
country: Japan
facility: Research Site
state: Tokyo
city: Minato-Ku
country: Japan
facility: Research Site
state: Tokyo
city: Mitaka-City
country: Japan
facility: Research Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Research Site
state: Tokyo
city: Kyoto
country: Japan
facility: Research Site
city: Nagasaki
country: Japan
facility: Research Site
city: Bundang-Gu, Seongnam-si
country: Korea, Republic of
facility: Research Site
state: Gyeonggi-do
city: Seo-gu
country: Korea, Republic of
facility: Research Site
state: Pusan
city: Gangnam-gu
country: Korea, Republic of
facility: Research Site
state: Seoul
city: Seodaemun-gu
country: Korea, Republic of
facility: Research Site
state: Seoul
city: Seongbuk-gu
country: Korea, Republic of
facility: Research Site
state: Seoul
city: Songpa-gu
country: Korea, Republic of
facility: Research Site
state: Seoul
city: Liepaja
country: Latvia
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Distrito Federal
country: Mexico
facility: Research Site
state: Ciudad de Mexico
city: Mexico DF
country: Mexico
facility: Research Site
state: Distrito Federal
city: Amsterdam
country: Netherlands
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city: Arnhem
country: Netherlands
facility: Research Site
city: Eindhoven
country: Netherlands
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city: Hertogenbosch
country: Netherlands
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city: Nijmegen
country: Netherlands
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city: Rotterdam
country: Netherlands
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city: Tilburg
country: Netherlands
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city: Tonsberg
country: Norway
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city: Trondheim
country: Norway
facility: Research Site
city: Arequipa
country: Peru
facility: Research Site
city: Bellavista
country: Peru
facility: Research Site
city: Jesus Maria
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Gdynia
country: Poland
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city: Kielce
country: Poland
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city: Koscierzyna
country: Poland
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city: Szczecin
country: Poland
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city: Warszawa
country: Poland
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city: Wroclaw
country: Poland
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city: Coimbra
country: Portugal
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city: Porto
country: Portugal
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city: Timisoara
country: Romania
facility: Research Site
state: Timis
city: Bucuresti
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
state: Omsk region
city: Izhevsk
country: Russian Federation
facility: Research Site
state: Russia
city: Tomsk
country: Russian Federation
facility: Research Site
state: Tomsk Region
city: Barnaul
country: Russian Federation
facility: Research Site
city: Kursk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Sochi
country: Russian Federation
facility: Research Site
city: St.Petersburg
country: Russian Federation
facility: Research Site
city: Voronezh
country: Russian Federation
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Nis
country: Serbia
facility: Research Site
city: Novi Sad
country: Serbia
facility: Research Site
city: Observatory
country: South Africa
facility: Research Site
state: Cape Town
city: Tygerberg
country: South Africa
facility: Research Site
state: Cape Town
city: Overport
country: South Africa
facility: Research Site
state: Durban
city: Parktown
country: South Africa
facility: Research Site
state: Johannesburg
city: Pietermaritzburg
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Elche
country: Spain
facility: Research Site
state: Alicante
city: Barakaldo
country: Spain
facility: Research Site
state: Bizkaia
city: Bilbao
country: Spain
facility: Research Site
state: Vizcaya
city: A Corunna
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Gothenburg
country: Sweden
facility: Research Site
city: Helsingborg
country: Sweden
facility: Research Site
city: Jonkoping
country: Sweden
facility: Research Site
city: Orebro
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Aarau
country: Switzerland
facility: Research Site
city: CH-4031 Basel
country: Switzerland
facility: Research Site
city: Locarno
country: Switzerland
facility: Research Site
city: Zuerich
country: Switzerland
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Reading
country: United Kingdom
facility: Research Site
state: Berkshire
city: Cottingham
country: United Kingdom
facility: Research Site
state: East Yorkshire
city: Stevenage
country: United Kingdom
facility: Research Site
state: Hertfordshire
city: Maidstone
country: United Kingdom
facility: Research Site
state: Kent
city: Guildford
country: United Kingdom
facility: Research Site
state: Surrey
city: Cambridge
country: United Kingdom
facility: Research Site
city: Coventry
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Huddersfield
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Charite University, Berlin, Germany
name: Kurt Miller, Prof., M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Tia Higano, MD
role: PRINCIPAL_INVESTIGATOR
References: