Efficacy and Safety of Insulin Glargine/ Lixisenatide Fixed Ratio Combination Compared to Insulin Glargine Alone and Lixisenatide Alone on Top of Metformin in Patients With T2DM
- Conditions
- Type 2 Diabetes
- Interventions
- Drug: Insulin glargine/lixisenatide Fixed Ratio CombinationDrug: Insulin glargine (HOE901)Drug: Lixisenatide (AVE0010)Drug: Metformin
- Registration Number
- NCT02058147
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To compare the insulin glargine/lixisenatide fixed ratio combination to lixisenatide alone and to insulin glargine alone (on top of metformin treatment) in glycated hemoglobin (HbA1c) change from baseline to Week 30.
Secondary Objective:
To compare the overall efficacy and safety of insulin glargine/lixisenatide fixed ratio combination (FRC) to insulin glargine alone and to lixisenatide alone (on top of metformin treatment) over a 30 week treatment period in participants with type 2 diabetes.
- Detailed Description
Approximately 37 weeks including up to 6 weeks of screening, 30-week treatment period, and a 3 days follow-up period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1170
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) Insulin glargine/lixisenatide Fixed Ratio Combination FRC once daily (QD) for 30 weeks. Dose individually adjusted. Insulin Glargine Insulin glargine (HOE901) Insulin glargine QD for 30 weeks. Dose individually adjusted. Insulin Glargine Metformin Insulin glargine QD for 30 weeks. Dose individually adjusted. Lixisenatide Lixisenatide (AVE0010) Lixisenatide 10 mcg QD for 2 weeks, then 20 mcg QD (maintenance dose). Lixisenatide Metformin Lixisenatide 10 mcg QD for 2 weeks, then 20 mcg QD (maintenance dose). Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) Metformin FRC once daily (QD) for 30 weeks. Dose individually adjusted.
- Primary Outcome Measures
Name Time Method Change in HbA1c From Baseline to Week 30 Baseline, Week 30 Primary outcome was to test superiority of FRC versus Lixisenatide and non-inferiority versus Insulin glargine.
Change in HbA1c was calculated by subtracting baseline value from Week 30 value.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With HbA1c <7.0% or ≤6.5% at Week 30 Week 30 Participants without Week 30 value for HbA1c were counted as non-responders.
Change in Plasma Glucose Excursion From Baseline to Week 30 Baseline, Week 30 Plasma glucose excursion = 2-hour postprandial plasma glucose (PPG) value minus plasma glucose value obtained 30 minutes prior to the start of meal and before investigational medicinal product (IMP) administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 30 value. Missing data was imputed using last observation carried forward (LOCF).
Change in Body Weight From Baseline to Week 30 Baseline, Week 30 Change in body weight was calculated by subtracting baseline value from Week 30 value.
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 30 Baseline, Week 30 Change in FPG was calculated by subtracting baseline value from Week 30 value.
Mean Change in 7-point Self-monitored Plasma Glucose (SMPG) Profile From Baseline to Week 30 Baseline, Week 30 Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime two times in a week before baseline, before visit Week 12 and before visit Week 30 and the average value across the profiles performed in the week before a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 30 value. The analysis included all scheduled measurements obtained during the study. The missing data was handled by mixed effect model with repeated measures (MMRM) approach.
Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30 Week 30 Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30 and No Documented Symptomatic Hypoglycemia (Plasma Glucose [PG] ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period Baseline up to Week 30 Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L).
Average Daily Insulin Glargine Dose at Week 30 Week 30 The analysis included scheduled measurements obtained up to the date of last injection of the IMP, including those obtained after introduction of rescue therapy.
Change in 2-Hour Postprandial Plasma Glucose (PPG) From Baseline to Week 30 Baseline, Week 30 The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 30 value. Missing data was imputed using LOCF.
Percentage of Participants Reaching HbA1c <7.0% at Week 30 With No Documented Symptomatic Hypoglycemia (PG ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period Baseline up to Week 30 Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L). The analysis included all HbA1c measurements at Week 30, including those obtained after the IMP discontinuation or the introduction of rescue medication.
Percentage of Participants Requiring Rescue Therapy During 30-Week Treatment Period Baseline up to Week 30 Routine fasting SMPG and central laboratory FPG (and HbA1c after Week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after Week 12) was performed. Threshold values - from Week 8 to Week 12: fasting SMPG/FPG \>240 mg/dL (13.3 mmol/L), and from Week 12 to Week 30: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8%.
Number of Documented Symptomatic Hypoglycemia Events Per Subject-Year First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days) Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤ 70 mg/dL (3.9 mmol/L).
Percentage of Participants With Documented Symptomatic Hypoglycemia First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days) Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤ 70 mg/dL (3.9 mmol/L).
Percentage of Participants With Severe Symptomatic Hypoglycemia First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days) Severe symptomatic hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Plasma glucose measurements might not have been available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal was considered sufficient evidence that the event had been induced by a low plasma glucose concentration. Severe symptomatic hypoglycemia included all episodes in which neurological impairment was severe enough to prevent self-treatment, and which were thus thought to place participants at risk of injury to themselves or others.
Trial Locations
- Locations (273)
Investigational Site Number 840023
🇺🇸Tempe, Arizona, United States
Investigational Site Number 840067
🇺🇸Santa Ana, California, United States
Investigational Site Number 840089
🇺🇸Atlanta, Georgia, United States
Investigational Site Number 840017
🇺🇸La Jolla, California, United States
Investigational Site Number 840104
🇺🇸Bradenton, Florida, United States
Investigational Site Number 840065
🇺🇸Bell Gardens, California, United States
Investigational Site Number 840119
🇺🇸Woodstock, Georgia, United States
Investigational Site Number 840081
🇺🇸New Orleans, Louisiana, United States
Investigational Site Number 840015
🇺🇸Avon, Indiana, United States
Investigational Site Number 840005
🇺🇸Northridge, California, United States
Investigational Site Number 840057
🇺🇸Butte, Montana, United States
Investigational Site Number 840028
🇺🇸Bloomfield Hills, Michigan, United States
Investigational Site Number 840076
🇺🇸Avon, Indiana, United States
Investigational Site Number 840082
🇺🇸Evansville, Indiana, United States
Investigational Site Number 840031
🇺🇸Evansville, Indiana, United States
Investigational Site Number 840022
🇺🇸Lexington, Kentucky, United States
Investigational Site Number 840096
🇺🇸Syracuse, New York, United States
Investigational Site Number 840126
🇺🇸Los Angeles, California, United States
Investigational Site Number 840054
🇺🇸Lawrenceville, Georgia, United States
Investigational Site Number 840021
🇺🇸Hickory, North Carolina, United States
Investigational Site Number 840123
🇺🇸Morganville, New Jersey, United States
Investigational Site Number 840024
🇺🇸Chesterfield, Missouri, United States
Investigational Site Number 840118
🇺🇸Fort Worth, Texas, United States
Investigational Site Number 840063
🇺🇸Rockville, Maryland, United States
Investigational Site Number 840088
🇺🇸Edinburg, Texas, United States
Investigational Site Number 840071
🇺🇸Chesterfield, Michigan, United States
Investigational Site Number 840066
🇺🇸Corpus Christi, Texas, United States
Investigational Site Number 840020
🇺🇸Dallas, Texas, United States
Investigational Site Number 840011
🇺🇸Albuquerque, New Mexico, United States
Investigational Site Number 840069
🇺🇸Nashua, New Hampshire, United States
Investigational Site Number 840037
🇺🇸Draper, Utah, United States
Investigational Site Number 840045
🇺🇸Norfolk, Virginia, United States
Investigational Site Number 840092
🇺🇸Norfolk, Virginia, United States
Investigational Site Number 124001
🇨🇦Toronto, Canada
Investigational Site Number 036007
🇦🇺Logan Central, Australia
Investigational Site Number 840111
🇺🇸Dallas, Texas, United States
Investigational Site Number 840064
🇺🇸Dallas, Texas, United States
Investigational Site Number 840093
🇺🇸Ogden, Utah, United States
Investigational Site Number 840115
🇺🇸Salem, Virginia, United States
Investigational Site Number 840102
🇺🇸Renton, Washington, United States
Investigational Site Number 124002
🇨🇦Vancouver, Canada
Investigational Site Number 840030
🇺🇸New Hyde Park, New York, United States
Investigational Site Number 152015
🇨🇱Puerto Varas, Chile
Investigational Site Number 124004
🇨🇦Kelowna, Canada
Investigational Site Number 840109
🇺🇸Henderson, Nevada, United States
Investigational Site Number 056005
🇧🇪Brussels, Belgium
Investigational Site Number 036001
🇦🇺Camperdown, Australia
Investigational Site Number 152001
🇨🇱Santiago, Chile
Investigational Site Number 152002
🇨🇱Santiago, Chile
Investigational Site Number 840003
🇺🇸Dallas, Texas, United States
Investigational Site Number 152004
🇨🇱Santiago, Chile
Investigational Site Number 152011
🇨🇱Talagante, Chile
Investigational Site Number 840110
🇺🇸Salisbury, North Carolina, United States
Investigational Site Number 208001
🇩🇰København Nv, Denmark
Investigational Site Number 840073
🇺🇸N Richland Hill, Texas, United States
Investigational Site Number 203009
🇨🇿Praha 2, Czech Republic
Investigational Site Number 233002
🇪🇪Pärnu, Estonia
Investigational Site Number 276007
🇩🇪Dresden, Germany
Investigational Site Number 276004
🇩🇪Dortmund, Germany
Investigational Site Number 348011
🇭🇺Komárom, Hungary
Investigational Site Number 348008
🇭🇺Nagykanizsa, Hungary
Investigational Site Number 208003
🇩🇰Aarhus C, Denmark
Investigational Site Number 348010
🇭🇺Szekesfehervar, Hungary
Investigational Site Number 233004
🇪🇪Paide, Estonia
Investigational Site Number 428003
🇱🇻Riga, Latvia
Investigational Site Number 276005
🇩🇪Berlin, Germany
Investigational Site Number 250001
🇫🇷Venissieux, France
Investigational Site Number 484002
🇲🇽Guadalajara, Mexico
Investigational Site Number 348007
🇭🇺Budapest, Hungary
Investigational Site Number 250003
🇫🇷Pierre Benite, France
Investigational Site Number 348012
🇭🇺Sátoraljaújhely, Hungary
Investigational Site Number 276003
🇩🇪Berlin, Germany
Investigational Site Number 380002
🇮🇹Bologna, Italy
Investigational Site Number 380006
🇮🇹Catanzaro, Italy
Investigational Site Number 348002
🇭🇺Budapest, Hungary
Investigational Site Number 348001
🇭🇺Zalaegerszeg, Hungary
Investigational Site Number 276001
🇩🇪Dresden, Germany
Investigational Site Number 380005
🇮🇹Roma, Italy
Investigational Site Number 348004
🇭🇺Szeged, Hungary
Investigational Site Number 440006
🇱🇹Panevezys, Lithuania
Investigational Site Number 440005
🇱🇹Utena, Lithuania
Investigational Site Number 348003
🇭🇺Balatonfüred, Hungary
Investigational Site Number 276002
🇩🇪Neumünster, Germany
Investigational Site Number 826006
🇬🇧Guildford, United Kingdom
Investigational Site Number 643006
🇷🇺Moscow, Russian Federation
Investigational Site Number 642001
🇷🇴Targu Mures, Romania
Investigational Site Number 826001
🇬🇧Coventry, United Kingdom
Investigational Site Number 643007
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 752005
🇸🇪Stockholm, Sweden
Investigational Site Number 710006
🇿🇦Soweto, South Africa
Investigational Site Number 710005
🇿🇦Meyerspark, South Africa
Investigational Site Number 643003
🇷🇺St. Petersburg, Russian Federation
Investigational Site Number 643014
🇷🇺Samara, Russian Federation
Investigational Site Number 724008
🇪🇸Madrid, Spain
Investigational Site Number 724009
🇪🇸Granada, Spain
Investigational Site Number 724007
🇪🇸Lugo, Spain
Investigational Site Number 643008
🇷🇺Penza, Russian Federation
Investigational Site Number 710004
🇿🇦Pretoria, South Africa
Investigational Site Number 724011
🇪🇸La Coruña, Spain
Investigational Site Number 826003
🇬🇧Norwich, United Kingdom
Investigational Site Number 642002
🇷🇴Oradea, Romania
Investigational Site Number 724005
🇪🇸Madrid, Spain
Investigational Site Number 642003
🇷🇴Timisoara, Romania
Investigational Site Number 710007
🇿🇦Port Elizabeth, South Africa
Investigational Site Number 724004
🇪🇸Hostalets De Balenyà, Spain
Investigational Site Number 724013
🇪🇸Palma De Mallorca, Spain
Investigational Site Number 804002
🇺🇦Chernivtsi, Ukraine
Investigational Site Number 804007
🇺🇦Kyiv, Ukraine
Investigational Site Number 804011
🇺🇦Vinnytsya, Ukraine
Investigational Site Number 642004
🇷🇴Timisoara, Romania
Investigational Site Number 724012
🇪🇸Barcelona, Spain
Investigational Site Number 804009
🇺🇦Ivano-Frankovsk, Ukraine
Investigational Site Number 804012
🇺🇦Lviv, Ukraine
Investigational Site Number 643004
🇷🇺Voronezh, Russian Federation
Investigational Site Number 710002
🇿🇦Cap Town, South Africa
Investigational Site Number 724001
🇪🇸Quart De Poblet, Spain
Investigational Site Number 804010
🇺🇦Kyiv, Ukraine
Investigational Site Number 826002
🇬🇧Dundee, United Kingdom
Investigational Site Number 440001
🇱🇹Vilnius, Lithuania
Investigational Site Number 203016
🇨🇿Ujezd U Brna, Czech Republic
Investigational Site Number 440002
🇱🇹Kaunas, Lithuania
Investigational Site Number 484010
🇲🇽Zapopan, Mexico
Investigational Site Number 616004
🇵🇱Szczecin, Poland
Investigational Site Number 642006
🇷🇴Hunedoara, Romania
Investigational Site Number 484001
🇲🇽Cuernavaca, Mexico
Investigational Site Number 484007
🇲🇽Monterrey, Mexico
Investigational Site Number 616007
🇵🇱Lodz, Poland
Investigational Site Number 616002
🇵🇱Bialystok, Poland
Investigational Site Number 616005
🇵🇱Krakow, Poland
Investigational Site Number 804008
🇺🇦Vinnytsya, Ukraine
Investigational Site Number 804006
🇺🇦Kyiv, Ukraine
Investigational Site Number 840026
🇺🇸Chicago, Illinois, United States
Investigational Site Number 840116
🇺🇸Chicago, Illinois, United States
Investigational Site Number 840098
🇺🇸Miami, Florida, United States
Investigational Site Number 840048
🇺🇸Indianapolis, Indiana, United States
Investigational Site Number 840052
🇺🇸Las Vegas, Nevada, United States
Investigational Site Number 840087
🇺🇸Houston, Texas, United States
Investigational Site Number 840041
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 840080
🇺🇸Chicago, Illinois, United States
Investigational Site Number 840085
🇺🇸Indianapolis, Indiana, United States
Investigational Site Number 840061
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 840019
🇺🇸San Antonio, Texas, United States
Investigational Site Number 840027
🇺🇸Phoenix, Arizona, United States
Investigational Site Number 840122
🇺🇸Phoenix, Arizona, United States
Investigational Site Number 208009
🇩🇰Horsens, Denmark
Investigational Site Number 752004
🇸🇪Rättvik, Sweden
Investigational Site Number 752002
🇸🇪Vällingby, Sweden
Investigational Site Number 840038
🇺🇸Denver, Colorado, United States
Investigational Site Number 840113
🇺🇸Portland, Oregon, United States
Investigational Site Number 643002
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 643016
🇷🇺Tomsk, Russian Federation
Investigational Site Number 840095
🇺🇸Wilmington, North Carolina, United States
Investigational Site Number 826007
🇬🇧Leicester, United Kingdom
Investigational Site Number 276006
🇩🇪Hamburg, Germany
Investigational Site Number 348006
🇭🇺Budapest, Hungary
Investigational Site Number 840059
🇺🇸Aurora, Colorado, United States
Investigational Site Number 840042
🇺🇸Omaha, Nebraska, United States
Investigational Site Number 840099
🇺🇸Winston-Salem, North Carolina, United States
Investigational Site Number 840062
🇺🇸Tempe, Arizona, United States
Investigational Site Number 840013
🇺🇸Concord, California, United States
Investigational Site Number 840090
🇺🇸Chino, California, United States
Investigational Site Number 840100
🇺🇸Anaheim, California, United States
Investigational Site Number 840084
🇺🇸Little Rock, Arkansas, United States
Investigational Site Number 840002
🇺🇸Chula Vista, California, United States
Investigational Site Number 840053
🇺🇸Fresno, California, United States
Investigational Site Number 840070
🇺🇸Lancaster, California, United States
Investigational Site Number 840121
🇺🇸Long Beach, California, United States
Investigational Site Number 840101
🇺🇸Mission Hills, California, United States
Investigational Site Number 840044
🇺🇸Los Angeles, California, United States
Investigational Site Number 840086
🇺🇸Mission Viejo, California, United States
Investigational Site Number 840120
🇺🇸Mission Viejo, California, United States
Investigational Site Number 840034
🇺🇸Palm Springs, California, United States
Investigational Site Number 840068
🇺🇸San Ramon, California, United States
Investigational Site Number 840074
🇺🇸Port Hueneme, California, United States
Investigational Site Number 840006
🇺🇸Temecula, California, United States
Investigational Site Number 840029
🇺🇸Tarzana, California, United States
Investigational Site Number 840078
🇺🇸West Hills, California, United States
Investigational Site Number 840014
🇺🇸New Port Richey, Florida, United States
Investigational Site Number 840056
🇺🇸Palm Harbor, Florida, United States
Investigational Site Number 840047
🇺🇸Ocoee, Florida, United States
Investigational Site Number 840108
🇺🇸Idaho Falls, Idaho, United States
Investigational Site Number 840075
🇺🇸Arlington Heights, Illinois, United States
Investigational Site Number 840050
🇺🇸Springfield, Illinois, United States
Investigational Site Number 840008
🇺🇸Avon, Indiana, United States
Investigational Site Number 840060
🇺🇸Evansville, Indiana, United States
Investigational Site Number 840025
🇺🇸Waterloo, Iowa, United States
Investigational Site Number 840012
🇺🇸Valparaiso, Indiana, United States
Investigational Site Number 840097
🇺🇸Auburn, Maine, United States
Investigational Site Number 840001
🇺🇸Dearborn, Michigan, United States
Investigational Site Number 840091
🇺🇸Kalamazoo, Michigan, United States
Investigational Site Number 840009
🇺🇸Minneapolis, Minnesota, United States
Investigational Site Number 840039
🇺🇸Asheville, North Carolina, United States
Investigational Site Number 840016
🇺🇸Maumee, Ohio, United States
Investigational Site Number 840004
🇺🇸Columbus, Ohio, United States
Investigational Site Number 840046
🇺🇸Morehead City, North Carolina, United States
Investigational Site Number 840072
🇺🇸Morganton, North Carolina, United States
Investigational Site Number 840103
🇺🇸Eugene, Oregon, United States
Investigational Site Number 840036
🇺🇸Pittsburgh, Pennsylvania, United States
Investigational Site Number 840049
🇺🇸Greer, South Carolina, United States
Investigational Site Number 840043
🇺🇸Tipton, Pennsylvania, United States
Investigational Site Number 840058
🇺🇸Anderson, South Carolina, United States
Investigational Site Number 840112
🇺🇸Bristol, Tennessee, United States
Investigational Site Number 840114
🇺🇸Rapid City, South Dakota, United States
Investigational Site Number 840051
🇺🇸Austin, Texas, United States
Investigational Site Number 840094
🇺🇸Knoxville, Tennessee, United States
Investigational Site Number 840079
🇺🇸Hurst, Texas, United States
Investigational Site Number 840055
🇺🇸Houston, Texas, United States
Investigational Site Number 840040
🇺🇸Chesapeake, Virginia, United States
Investigational Site Number 840010
🇺🇸Weber City, Virginia, United States
Investigational Site Number 152014
🇨🇱Temuco, Chile
Investigational Site Number 840077
🇺🇸Federal Way, Washington, United States
Investigational Site Number 840033
🇺🇸Milwaukee, Wisconsin, United States
Investigational Site Number 036005
🇦🇺Box Hill, Australia
Investigational Site Number 056006
🇧🇪Brussel, Belgium
Investigational Site Number 036006
🇦🇺Kippa Ring, Australia
Investigational Site Number 056001
🇧🇪Leuven, Belgium
Investigational Site Number 152008
🇨🇱Osorno, Chile
Investigational Site Number 152003
🇨🇱Temuco, Chile
Investigational Site Number 203008
🇨🇿Ceske Budejovice, Czech Republic
Investigational Site Number 203004
🇨🇿Beroun, Czech Republic
Investigational Site Number 203014
🇨🇿Horovice, Czech Republic
Investigational Site Number 203012
🇨🇿Koprivnice, Czech Republic
Investigational Site Number 203005
🇨🇿Plzen, Czech Republic
Investigational Site Number 203003
🇨🇿Praha 10, Czech Republic
Investigational Site Number 203013
🇨🇿Praha 9 - Klanovice, Czech Republic
Investigational Site Number 208002
🇩🇰Kolding, Denmark
Investigational Site Number 208005
🇩🇰København S, Denmark
Investigational Site Number 208004
🇩🇰Viborg, Denmark
Investigational Site Number 250002
🇫🇷La Rochelle Cedex, France
Investigational Site Number 250006
🇫🇷Corbeil Essonnes, France
Investigational Site Number 380003
🇮🇹Napoli, Italy
Investigational Site Number 380001
🇮🇹Milano, Italy
Investigational Site Number 428002
🇱🇻Riga, Latvia
Investigational Site Number 428004
🇱🇻Riga, Latvia
Investigational Site Number 428001
🇱🇻Sigulda, Latvia
Investigational Site Number 440003
🇱🇹Jonava, Lithuania
Investigational Site Number 440007
🇱🇹Kaunas, Lithuania
Investigational Site Number 484004
🇲🇽Guadalajara, Mexico
Investigational Site Number 484005
🇲🇽Aguascalientes, Mexico
Investigational Site Number 484006
🇲🇽Monterrey, Mexico
Investigational Site Number 642009
🇷🇴Cluj Napoca, Romania
Investigational Site Number 616003
🇵🇱Warszawa, Poland
Investigational Site Number 616006
🇵🇱Krakow, Poland
Investigational Site Number 616001
🇵🇱Warszawa, Poland
Investigational Site Number 642008
🇷🇴Bucharest, Romania
Investigational Site Number 642007
🇷🇴Bucuresti, Romania
Investigational Site Number 643001
🇷🇺Saint-Petersburg, Russian Federation
Investigational Site Number 642005
🇷🇴Iasi, Romania
Investigational Site Number 643012
🇷🇺Petrozavodsk, Russian Federation
Investigational Site Number 643011
🇷🇺Saratov, Russian Federation
Investigational Site Number 643005
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 643009
🇷🇺Saratov, Russian Federation
Investigational Site Number 710003
🇿🇦Cape Town, South Africa
Investigational Site Number 710001
🇿🇦Somerset West, South Africa
Investigational Site Number 752001
🇸🇪Ljungby, Sweden
Investigational Site Number 724003
🇪🇸Sevilla, Spain
Investigational Site Number 752003
🇸🇪Malmö, Sweden
Investigational Site Number 724006
🇪🇸Sant Joan Despí, Spain
Investigational Site Number 152006
🇨🇱Santiago, Chile
Investigational Site Number 152012
🇨🇱Santiago, Chile
Investigational Site Number 203001
🇨🇿Pardubice, Czech Republic
Investigational Site Number 233003
🇪🇪Tallinn, Estonia
Investigational Site Number 233001
🇪🇪Viljandimaa, Estonia
Investigational Site Number 152009
🇨🇱Santiago, Chile
Investigational Site Number 203006
🇨🇿Trutnov, Czech Republic
Investigational Site Number 203015
🇨🇿Vsetin, Czech Republic
Investigational Site Number 203007
🇨🇿Praha 5, Czech Republic
Investigational Site Number 440004
🇱🇹Kedainiai, Lithuania
Investigational Site Number 484009
🇲🇽Guadalajara, Mexico
Investigational Site Number 616008
🇵🇱Zory, Poland
Investigational Site Number 840007
🇺🇸Louisville, Kentucky, United States
Investigational Site Number 840127
🇺🇸Charleston, South Carolina, United States
Investigational Site Number 840125
🇺🇸Richmond, Virginia, United States