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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05583344




Registration number
NCT05583344
Ethics application status
Date submitted
13/10/2022
Date registered
17/10/2022

Titles & IDs
Public title
Phase 2b Study of GSK4532990 in Adults With NASH
Scientific title
17 ß-Hydroxysteroid Dehydrogenase Type 13 Minimization for the Treatment of NASH (HORIZON): A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of GSK4532990 in Adults With Nonalcoholic Steatohepatitis
Secondary ID [1] 0 0
2022-002538-14
Secondary ID [2] 0 0
218672
Universal Trial Number (UTN)
Trial acronym
HORIZON
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nonalcoholic Fatty Liver Disease 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Liver
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Diet and Nutrition 0 0 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK4532990
Treatment: Drugs - Placebo

Experimental: High Dose GSK4532990 -

Experimental: Low Dose GSK4532990 -

Placebo comparator: Placebo -


Treatment: Drugs: GSK4532990
GSK4532990 will be administered.

Treatment: Drugs: Placebo
Placebo will be administered.

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

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving = 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH - F3 Cohort
Timepoint [1] 0 0
At Week 52
Primary outcome [2] 0 0
Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis - F3 Cohort
Timepoint [2] 0 0
At Week 52
Secondary outcome [1] 0 0
Percentage of Participants Achieving = 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH - Pooled Cohort (F3 participants and F4 participants)
Timepoint [1] 0 0
At Week 52
Secondary outcome [2] 0 0
Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis - Pooled Cohort (F3 participants and F4 participants)
Timepoint [2] 0 0
At Week 52
Secondary outcome [3] 0 0
Change from baseline in Pro-peptide of type III collagen (Pro-C3) - F3 Cohort
Timepoint [3] 0 0
Baseline (Day 1) and at Week 24 and 52
Secondary outcome [4] 0 0
Change from baseline in liver fat using Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) - F3 Cohort
Timepoint [4] 0 0
Baseline (Day 1) and at Week 24 and 52
Secondary outcome [5] 0 0
Change from baseline in Liver stiffness measurement (LSM) by Vibration-controlled transient elastography (VCTE) - F3 Cohort
Timepoint [5] 0 0
Baseline (Day 1) and at Week 24 and 52
Secondary outcome [6] 0 0
Change from baseline in Enhanced Liver Fibrosis (ELF) Score - F3 Cohort
Timepoint [6] 0 0
Baseline (Day 1) and at Week 24 and 52
Secondary outcome [7] 0 0
Percentage of Participants Achieving =30% relative reduction in liver fat from baseline using MRI-PDFF at Week 24- F3 Cohort
Timepoint [7] 0 0
At Week 24
Secondary outcome [8] 0 0
Percentage of Participants Achieving =30% relative reduction in liver fat from baseline using MRI-PDFF at Week 52 - F3 Cohort
Timepoint [8] 0 0
At Week 52
Secondary outcome [9] 0 0
Change from Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma-glutamyl transferase (GGT) (Units Per Liter) - F3 Cohort
Timepoint [9] 0 0
Baseline (Day 1) and at Week 24 and 52
Secondary outcome [10] 0 0
Change from baseline in Pro-peptide of type III collagen (Pro-C3) - Pooled Cohort (F3 participants and F4 participants)
Timepoint [10] 0 0
Baseline (Day 1) and at Week 24 and 52
Secondary outcome [11] 0 0
Change from baseline in liver fat using Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) - Pooled Cohort (F3 participants and F4 participants)
Timepoint [11] 0 0
Baseline (Day 1) and at Week 24 and 52
Secondary outcome [12] 0 0
Change from baseline in Liver stiffness measurement (LSM) by Vibration-controlled transient elastography (VCTE) - Pooled Cohort (F3 participants and F4 participants)
Timepoint [12] 0 0
Baseline (Day 1) and at Week 24 and 52
Secondary outcome [13] 0 0
Change from baseline in Enhanced Liver Fibrosis (ELF) Score - Pooled Cohort (F3 participants and F4 participants)
Timepoint [13] 0 0
Baseline (Day 1) and at Week 24 and 52
Secondary outcome [14] 0 0
Percentage of Participants Achieving =30% relative reduction in liver fat from baseline using MRI-PDFF at Week 24 - Pooled Cohort (F3 participants and F4 participants)
Timepoint [14] 0 0
At Week 24
Secondary outcome [15] 0 0
Percentage of Participants Achieving =30% relative reduction in liver fat from baseline using MRI-PDFF at Week 52 - Pooled Cohort (F3 participants and F4 participants)
Timepoint [15] 0 0
At Week 52
Secondary outcome [16] 0 0
Change from Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma-glutamyl transferase (GGT) (Units Per Liter) - Pooled Cohort (F3 participants and F4 participants)
Timepoint [16] 0 0
Baseline (Day 1) and at Week 24 and 52
Secondary outcome [17] 0 0
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - F3 Cohort
Timepoint [17] 0 0
Up to Week 66
Secondary outcome [18] 0 0
Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - F3 Cohort
Timepoint [18] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [19] 0 0
Change from Baseline in Vital Signs - Temperature (Celsius) - F3 Cohort
Timepoint [19] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [20] 0 0
Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - F3 Cohort
Timepoint [20] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [21] 0 0
Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - F3 Cohort
Timepoint [21] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [22] 0 0
Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) - F3 Cohort
Timepoint [22] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [23] 0 0
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - F4 Cohort
Timepoint [23] 0 0
Up to Week 66
Secondary outcome [24] 0 0
Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - F4 Cohort
Timepoint [24] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [25] 0 0
Change from Baseline in Vital Signs - Temperature (Celsius) - F4 Cohort
Timepoint [25] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [26] 0 0
Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - F4 Cohort
Timepoint [26] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [27] 0 0
Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - F4 Cohort
Timepoint [27] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [28] 0 0
Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) - F4 Cohort
Timepoint [28] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [29] 0 0
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - Pooled Cohort (F3 participants and F4 participants)
Timepoint [29] 0 0
Up to Week 66
Secondary outcome [30] 0 0
Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - Pooled Cohort (F3 participants and F4 participants)
Timepoint [30] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [31] 0 0
Change from Baseline in Vital Signs - Temperature (Celsius) - Pooled Cohort (F3 participants and F4 participants)
Timepoint [31] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [32] 0 0
Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - Pooled Cohort (F3 participants and F4 participants)
Timepoint [32] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [33] 0 0
Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - Pooled Cohort (F3 participants and F4 participants)
Timepoint [33] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [34] 0 0
Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) - Pooled Cohort (F3 participants and F4 participants)
Timepoint [34] 0 0
Baseline (Day 1) and up to Week 52
Secondary outcome [35] 0 0
Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of GSK4532990 - F3 Cohort
Timepoint [35] 0 0
Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose
Secondary outcome [36] 0 0
Maximum observed concentration (Cmax) of GSK4532990- F3 Cohort
Timepoint [36] 0 0
Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose
Secondary outcome [37] 0 0
Percentage of Participants with Anti-drug Antibodies (ADA) to GSK4532990- F3 Cohort
Timepoint [37] 0 0
Up to Week 52
Secondary outcome [38] 0 0
Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of GSK4532990 - F4 Cohort
Timepoint [38] 0 0
Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose
Secondary outcome [39] 0 0
Maximum observed concentration (Cmax) of GSK4532990- F4 Cohort
Timepoint [39] 0 0
Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose
Secondary outcome [40] 0 0
Percentage of Participants with Anti-drug Antibodies (ADA) to GSK4532990- F4 Cohort
Timepoint [40] 0 0
Up to Week 52

Eligibility
Key inclusion criteria
* Body Mass Index (BMI) =25 kilogram per meter square (kg/m^2) (all ethnic origins) except for Asian participants who qualify for the study with BMI =23 kg/m2 at Screening.
* In the opinion of the investigator, there are features of metabolic syndrome and NAFLD is the most likely cause of liver disease. Metabolic syndrome may include type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and hypertension.
* A liver biopsy at baseline showing NAFLD Activity Score (NAS) >=4 with at least 1 point each in steatosis, inflammation and ballooning and either Fibrosis 3 or Fibrosis 4 using NASH CRN Scoring System.
* Able and willing to comply with all study assessments, including a liver biopsy at Week 52.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Current alcohol consumption =14 standard drinks (24 units, 196 g ethanol) per week for females or =21 standard drinks (37 units, 294g ethanol) per week for males.
* Weight reduction surgery or procedures (including gastric banding and intragastric balloon insertion) within 2 years of Screening 1 and/or planned during the study.
* History of cancer within previous 2 years from Screening 1, except basal or squamous cell carcinoma of the skin or in situ cervical carcinoma or any other type of cancer which has been treated medically or surgically with curative outcome.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Campbelltown
Recruitment hospital [2] 0 0
GSK Investigational Site - Nedlands
Recruitment hospital [3] 0 0
GSK Investigational Site - Perth
Recruitment postcode(s) [1] 0 0
2560 - Campbelltown
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment postcode(s) [3] 0 0
6000 - Perth
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
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Louisiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Nevada
Country [15] 0 0
United States of America
State/province [15] 0 0
New Jersey
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
State/province [19] 0 0
Pennsylvania
Country [20] 0 0
United States of America
State/province [20] 0 0
Tennessee
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Utah
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
United States of America
State/province [24] 0 0
Washington
Country [25] 0 0
Argentina
State/province [25] 0 0
Buenos Aires
Country [26] 0 0
Argentina
State/province [26] 0 0
Tucumán
Country [27] 0 0
Argentina
State/province [27] 0 0
Santa Fe
Country [28] 0 0
Belgium
State/province [28] 0 0
Brussels
Country [29] 0 0
Belgium
State/province [29] 0 0
Bruxelles
Country [30] 0 0
Belgium
State/province [30] 0 0
Edegem
Country [31] 0 0
Canada
State/province [31] 0 0
Alberta
Country [32] 0 0
Canada
State/province [32] 0 0
Ontario
Country [33] 0 0
France
State/province [33] 0 0
Angers Cedex 9
Country [34] 0 0
France
State/province [34] 0 0
Limoges cedex
Country [35] 0 0
France
State/province [35] 0 0
Paris Cedex 13
Country [36] 0 0
France
State/province [36] 0 0
Pessac cedex
Country [37] 0 0
France
State/province [37] 0 0
Pierre-Bénite
Country [38] 0 0
France
State/province [38] 0 0
Strasbourg Cedex
Country [39] 0 0
Greece
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Athens
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Greece
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Rio
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Greece
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Thessaloniki
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India
State/province [42] 0 0
Assam
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India
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Gujarat
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India
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Maharashtra
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India
State/province [45] 0 0
Punjab
Country [46] 0 0
India
State/province [46] 0 0
Tamil Nadu
Country [47] 0 0
India
State/province [47] 0 0
Bhubaneshwar, Odisha
Country [48] 0 0
India
State/province [48] 0 0
Chandigarh
Country [49] 0 0
India
State/province [49] 0 0
Nagpur
Country [50] 0 0
India
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New Delhi
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India
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Secunderabad
Country [52] 0 0
Italy
State/province [52] 0 0
Emilia-Romagna
Country [53] 0 0
Italy
State/province [53] 0 0
Lazio
Country [54] 0 0
Italy
State/province [54] 0 0
Lombardia
Country [55] 0 0
Italy
State/province [55] 0 0
Puglia
Country [56] 0 0
Italy
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Sicilia
Country [57] 0 0
Italy
State/province [57] 0 0
Toscana
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Italy
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Veneto
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Japan
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Fukui
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Japan
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Fukuoka
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Japan
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Gifu
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Japan
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Hiroshima
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Japan
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Iwate
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Japan
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Kagawa
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Japan
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Kagoshima
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Japan
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Kanagawa
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Japan
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Kyoto
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Japan
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Nagano
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Japan
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Nagasaki
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Japan
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Nara
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Japan
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Okayama
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Japan
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Osaka
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Japan
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Saga
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Japan
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Shimane
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Japan
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Yamanashi
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Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul
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Mexico
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Jalisco
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Mexico
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Morelos
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Mexico
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Aguascalientes
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Mexico
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Merida
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Panama
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Ciudad de Panama
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Panama
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Panama
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Puerto Rico
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San Juan
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Majadahonda (Madrid)
Country [88] 0 0
Spain
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Málaga
Country [89] 0 0
Spain
State/province [89] 0 0
Pontevedra
Country [90] 0 0
Spain
State/province [90] 0 0
Sabadell (Barcelona)
Country [91] 0 0
Spain
State/province [91] 0 0
Santander
Country [92] 0 0
Spain
State/province [92] 0 0
Sevilla
Country [93] 0 0
Turkey
State/province [93] 0 0
Ankara
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Turkey
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Gaziantep
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Turkey
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Izmir
Country [96] 0 0
Turkey
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Kocaeli
Country [97] 0 0
Turkey
State/province [97] 0 0
Rize
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Staffordshire
Country [99] 0 0
United Kingdom
State/province [99] 0 0
Barnsley
Country [100] 0 0
United Kingdom
State/province [100] 0 0
Liverpool
Country [101] 0 0
United Kingdom
State/province [101] 0 0
London
Country [102] 0 0
United Kingdom
State/province [102] 0 0
Manchester
Country [103] 0 0
United Kingdom
State/province [103] 0 0
Newcastle Upon Tyne
Country [104] 0 0
United Kingdom
State/province [104] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
Available to whom?
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Available for what types of analyses?
How or where can data be obtained?


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.