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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02319044




Registration number
NCT02319044
Ethics application status
Date submitted
12/12/2014
Date registered
18/12/2014

Titles & IDs
Public title
Phase II Study of MEDI4736, Tremelimumab, and MEDI4736 in Combination w/ Tremelimumab Squamous Cell Carcinoma of the Head and Neck
Scientific title
A Phase II, Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Monotherapy, Tremelimumab Monotherapy, and MEDI4736 in Combination With Tremelimumab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Secondary ID [1] 0 0
D4193C00003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent/Metastatic Squamous Cell Carcinoma of Head & Neck 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MEDI4736
Treatment: Drugs - Tremelimumab
Treatment: Drugs - MEDI4736 + Tremelimumab

Experimental: MEDI4736 - MEDI4736 monotherapy

Experimental: Tremelimumab - Tremelimumab monotherapy

Experimental: MEDI4736 + Tremelimumab - MEDI4736 + Tremelimumab combination therapy


Treatment: Drugs: MEDI4736
MEDI4736 monotherapy

Treatment: Drugs: Tremelimumab
Tremelimumab monotherapy

Treatment: Drugs: MEDI4736 + Tremelimumab
MEDI4736 + Tremelimumab combination therapy
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate at 6 Months
Assessment method [1] 0 0
Objective response rate, primary analysis, based on BICR assessments according to RECIST v1.1. The number (%) of patients with a response excludes unconfirmed responses
Timepoint [1] 0 0
After 6 months
Primary outcome [2] 0 0
Objective Response Rate at 12 Months
Assessment method [2] 0 0
Objective response rate (per RECIST 1.1 as assessed by blinded independent central review \[BICR\]) is defined as the number (%) of patients with a confirmed complete response or confirmed partial response and will be based on all treated patients who are PD-L1-positive with measurable disease at baseline per BICR. Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1. criteria are: Complete response \[CR\] = disappearance of all target lesions since baseline; and partial response \[PR\] = at least a 30% decrease in the sum of the diameters of target lesions.
Timepoint [2] 0 0
After 12 months
Secondary outcome [1] 0 0
Best Objective Response
Assessment method [1] 0 0
The best response a patient has had during their time in the study
Timepoint [1] 0 0
After 12 months
Secondary outcome [2] 0 0
Duration of Response - Participants Remaining in Response
Assessment method [2] 0 0
Participants remaining in response - based on BICR assessments according to RECIST v1.1. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.
Timepoint [2] 0 0
After 12 months
Secondary outcome [3] 0 0
Time to Response
Assessment method [3] 0 0
Time to response in patients with objective response based on BICR assessments according to RECIST 1.1
Timepoint [3] 0 0
After 12 months
Secondary outcome [4] 0 0
Time to Onset of Response From First Dose
Assessment method [4] 0 0
Time to onset of response in patients with objective response based on BICR assessments according to RECIST 1.1
Timepoint [4] 0 0
After 12 months
Secondary outcome [5] 0 0
Disease Control Rate (DCR)
Assessment method [5] 0 0
Disease control rate (DCR) at 6 months based on BICR assessments according to RECIST v1.1. DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD). -Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following randomization. -Method 2: Patients who had a best objective response of CR or PR in the first 24 weeks or who had demonstrated SD for a minimum interval of 16 weeks following randomization.
Timepoint [5] 0 0
After 6 months
Secondary outcome [6] 0 0
Disease Control Rate (DCR)
Assessment method [6] 0 0
Disease control rate (DCR) at 12 months based on BICR assessments according to RECIST v1.1. DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD). -Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following randomization. -Method 2: Patients who had a best objective response of CR or PR in the first 24 weeks or who had demonstrated SD for a minimum interval of 16 weeks following randomization.
Timepoint [6] 0 0
After 12 months
Secondary outcome [7] 0 0
Progression-free Survival (PFS)
Assessment method [7] 0 0
Progression status at 6 months based on BICR assessments according to RECIST v1.1 at time of Progression Free Survival (PFS) analysis. Progression was defined as the time from the data of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. -Target Lesions, Non Target Lesions and New Lesions are not necessarily mutually exclusive categories. -Progression death refers to death in the absence of RECIST 1.1 progression.
Timepoint [7] 0 0
After 6 months
Secondary outcome [8] 0 0
Progression-free Survival (PFS)
Assessment method [8] 0 0
Progression status at 12 months based on BICR assessments according to RECIST v1.1 at time of Progression Free Survival (PFS) analysis. Progression was defined as the time from the data of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. -Target Lesions, Non Target Lesions and New Lesions are not necessarily mutually exclusive categories. -Progression death refers to death in the absence of RECIST 1.1 progression.
Timepoint [8] 0 0
After 12 months
Secondary outcome [9] 0 0
Overall Survival
Assessment method [9] 0 0
Survival status at time of overall survival analysis. 'Still in survival follow-up' includes patients known to be alive at data cut-off. 'Terminated prior to death' includes patients with unknown survival status or patients who were lost to follow-up.
Timepoint [9] 0 0
After 12 months
Secondary outcome [10] 0 0
Quality of Life
Assessment method [10] 0 0
Improvement in quality of life was assessed using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires: -The impact of treatment on Health-Related Quality of Life, functioning, and symptoms was evaluated using the EORTC QLQ-C30 v3. -Head and neck cancer-specific symptoms were evaluated using the EORTC QLQ-H\&N35. The symptom and QoL/function improvement rate was defined as the number (%) of patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score =10 or EORTC QLQ-C30 scales) in that symptom/function from baseline. For QLQ-H\&N35A a minimum clinically meaningful change was defined as a change in the score from baseline of \>10 for scales/items
Timepoint [10] 0 0
After 12 months
Secondary outcome [11] 0 0
Duration of Response
Assessment method [11] 0 0
Duration of objective response in patients with objective response based on BICR assessments according to RECIST v1.1. Duration of response was the time from the first documentation of Complete response/Partial response (which was subsequently confirmed) until the date of progression, death, or the last evaluable RECIST assessment for patients that did not progress. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off (per RECIST v1.1 as assessed by BICR).
Timepoint [11] 0 0
After 12 months

Eligibility
Key inclusion criteria
* Age =18 years;
* Written informed consent obtained from the patient/legal representative;
* Histologically confirmed recurrent or metastatic SCCHN; tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent; Patients who have only received chemo-radiation with curative intent for treatment of their locally advanced disease or recurrent disease are not eligible. Patients who received concurrent chemo-radiation as part of treatment of their recurrent disease are also not eligible.
* Written consent to provide newly acquired tumor tissue (preferred) or archival tissue for the purpose of establishing PD-L1 status.
* Confirmed PD-L1-negative SCCHN by Ventana SP263;
* WHO/ECOG performance status of 0 or 1;
* At least 1 measurable lesion at baseline;
* No prior exposure to immune-mediated therapy;
* Adequate organ and marrow function; Evidence of post-menopausal status or negative urinary or serum pregnancy test.
Minimum age
18 Years
Maximum age
96 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Histologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck;
* Received more than 1 regimen for recurrent or metastatic disease
* Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment;
* Receipt of any investigational anticancer therapy within 28 days or 5 half-lives;
* Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment;
* Major surgical procedure within 28 days prior to the first dose of Investigational Product;
* Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criterion;
* Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned Investigational Product;
* History of allogeneic organ transplantation;
* Active or prior documented autoimmune or inflammatory disorders;
* Uncontrolled intercurrent illness;
* another primary malignancy
* Patients with history of brain metastases, spinal cord compression, or a history of leptomeningeal carcinomatosis;
* History of active primary immunodeficiency;
* Known history of previous tuberculosis;
* Active infection including hepatitis B, hepatitis C or human immunodeficiency virus (HIV);
* Receipt of live, attenuated vaccine within 30 days prior to the first dose of Investigational Product;
* Pregnant or breast-feeding female patients;
* Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction
* Known allergy or hypersensitivity to Investigational Product.
* Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of patient safety or study results

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/04/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/07/2020
Sample size
Target
Accrual to date
Final
267
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Adelaide
Recruitment hospital [2] 0 0
Research Site - Darlinghurst
Recruitment hospital [3] 0 0
Research Site - Tweed Heads
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2485 - Tweed Heads
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
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Minnesota
Country [14] 0 0
United States of America
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Missouri
Country [15] 0 0
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New Hampshire
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United States of America
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New York
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North Carolina
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United States of America
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Oregon
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United States of America
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Pennsylvania
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United States of America
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South Carolina
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United States of America
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Tennessee
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Texas
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West Virginia
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Wisconsin
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Belgium
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Brussels
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Belgium
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Charleroi
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Belgium
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Kortrijk
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Belgium
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Leuven
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Belgium
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Namur
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Canada
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Alberta
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Canada
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New Brunswick
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Canada
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Ontario
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Canada
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Quebec
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Czechia
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Olomouc
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Czechia
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Zlin
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France
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Angers
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France
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Bordeaux
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France
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Brest
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Dijon
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Le Mans
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Lille cedex
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Lorient cedex
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Lyon Cedex 08
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Montpellier
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Nice
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Rouen
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Saint Brieuc
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St Grégoire
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France
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Strasbourg Cedex
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France
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Toulouse Cedex 9
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France
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Villejuif Cedex
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Georgia
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Batumi
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Georgia
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Tbilisi
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Germany
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Berlin
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Germany
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Halle
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Hannover
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Heidelberg
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Leipzig
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München
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Hungary
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Budapest
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Hungary
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Gyula
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Györ
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Hungary
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Kecskemét
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Miskolc
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Hungary
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Zalaegerszeg
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Israel
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Haifa
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Israel
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Petach-Tikva
Country [68] 0 0
Israel
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Tel Hashomer
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Korea, Republic of
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Daegu
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Korea, Republic of
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Goyang-si
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Korea, Republic of
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Suwon
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Malaysia
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Kuala Lumpur
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Malaysia
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Kuching
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Spain
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Barakaldo
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Spain
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Barcelona
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Spain
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Gerona
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Spain
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Granada
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Spain
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Jaén
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Spain
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Madrid
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Spain
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Malaga
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Spain
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Marbella (Málaga)
Country [82] 0 0
Spain
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Valencia
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Spain
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Zaragoza
Country [84] 0 0
Taiwan
State/province [84] 0 0
Taipei
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United Kingdom
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Aberdeen
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United Kingdom
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Birmingham
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United Kingdom
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Glasgow
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United Kingdom
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London
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Manchester
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
PRA Health Sciences
Country [1] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Magdalena Wrona
Address 0 0
Medical Scientist AstraZeneca Magdalena.Wrona@astrazeneca.com
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02319044