Long-term Safety and Tolerability of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY Long Term)
- Conditions
- Hypercholesterolemia
- Interventions
- Registration Number
- NCT01507831
- Lead Sponsor
- Sanofi
- Brief Summary
Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).
Primary Objective of the study:
To evaluate the long-term safety and tolerability of alirocumab in high cardiovascular risk participants with hypercholesterolemia not adequately controlled with their current lipid modifying therapy (LMT).
Secondary Objectives:
* To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks of treatment in comparison with placebo.
* To evaluate the effect of alirocumab in comparison with placebo on LDL-C at other time points.
* To evaluate the effects of alirocumab on other lipid parameters.
- Detailed Description
The maximum study duration was to be 89 weeks per participant, including a 3-week screening period, a 78-week randomized treatment period and 8-week follow-up period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2341
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo (for alirocumab) Placebo (for alirocumab) every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 78 weeks. Placebo Lipid-Modifying Therapy (LMT) Placebo (for alirocumab) every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 78 weeks. Alirocumab Lipid-Modifying Therapy (LMT) Alirocumab 150 mg Q2W added to stable LMT for 78 weeks. Alirocumab Alirocumab Alirocumab 150 mg Q2W added to stable LMT for 78 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Experienced Adverse Events (AEs) Up to 10 weeks after last study drug administration (maximum of 86 weeks) Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis From Baseline to Week 52 Measured LDL-C values via beta quantification method. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis From Baseline to Week 52 Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Percent Change From Baseline in Apo A1 at Week 24 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis From Baseline to Week 52 Adjusted least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were used in the model (ITT analysis).
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection) (on-treatment analysis).
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percentage of Very High Cardiovascular (CV) Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis Up to Week 52 Very high CV risk: Heterozygous Familial Hypercholesterolemia (heFH) participants with coronary heart disease (CHD) or CHD risk equivalents or non- Familial Hypercholesterolemia (FH). High CV risk: heFH participants without CHD or CHD risk equivalents. CHD risk equivalent: peripheral arterial disease, ischemic stroke, moderate chronic kidney disease (estimated glomerular filtration rate, 30 to \<60 ml/minute/1.73 m\^2 of body-surface area), or diabetes mellitus plus 2 or more additional risk factors (hypertension; ankle-brachial index of ≤0.90; microalbuminuria, macroalbuminuria, or a urinary dipstick result of \>2+ protein; preproliferative or proliferative retinopathy or laser treatment for retinopathy; or family history of premature CHD). Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were included in imputation model.
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis Up to Week 52 Adjusted percentages at Week 24 were from multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis From Baseline to Week 52 Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis From Baseline to Week 52 Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment were included in the imputation model.
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis Up to Week 52 Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were included in the imputation model.
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis Up to Week 52 Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 52 (i.e. up to 21 days after last injection).
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Apo A1 at Week 12 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis From Baseline to Week 52 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis From Baseline to Week 52 Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Trial Locations
- Locations (320)
Investigational Site Number 840047
🇺🇸Houston, Texas, United States
Investigational Site Number 840076
🇺🇸Long Beach, California, United States
Investigational Site Number 840163
🇺🇸Santa Rosa, California, United States
Investigational Site Number 840207
🇺🇸Fresno, California, United States
Investigational Site Number 840159
🇺🇸Huntsville, Alabama, United States
Investigational Site Number 840214
🇺🇸Pasadena, California, United States
Investigational Site Number 840101
🇺🇸Lincoln, California, United States
Investigational Site Number 840194
🇺🇸Beverly Hills, California, United States
Investigational Site Number 840086
🇺🇸Colorado Springs, Colorado, United States
Investigational Site Number 840182
🇺🇸Crystal River, Florida, United States
Investigational Site Number 840150
🇺🇸Atlantis, Florida, United States
Investigational Site Number 840002
🇺🇸Daytona Beach, Florida, United States
Investigational Site Number 840242
🇺🇸Clearwater, Florida, United States
Investigational Site Number 840164
🇺🇸Sarasota, Florida, United States
Investigational Site Number 840175
🇺🇸Sarasota, Florida, United States
Investigational Site Number 840003
🇺🇸St. Petersburg, Florida, United States
Investigational Site Number 840154
🇺🇸Lake Mary, Florida, United States
Investigational Site Number 840151
🇺🇸Ocala, Florida, United States
Investigational Site Number 840168
🇺🇸Ponte Vedra, Florida, United States
Investigational Site Number 840070
🇺🇸Fort Worth, Texas, United States
Investigational Site Number 840046
🇺🇸Jersey Shore, Pennsylvania, United States
Investigational Site Number 032007
🇦🇷Zarate, Argentina
Investigational Site Number 100014
🇧🇬Plovdiv, Bulgaria
Investigational Site Number 484004
🇲🇽Mexico, Mexico
Investigational Site Number 100012
🇧🇬Sofia, Bulgaria
Investigational Site Number 100009
🇧🇬Sofia, Bulgaria
Investigational Site Number 484008
🇲🇽Not Provided, Mexico
Investigational Site Number 380010
🇮🇹Zingonia-Osio Sotto, Italy
Investigational Site Number 203007
🇨🇿Praha 5, Czech Republic
Investigational Site Number 152007
🇨🇱Osorno, Chile
Investigational Site Number 528011
🇳🇱Hoogeveen, Netherlands
Investigational Site Number 528012
🇳🇱Venlo, Netherlands
Investigational Site Number 380007
🇮🇹Napoli, Italy
Investigational Site Number 484002
🇲🇽Tijuana, Mexico
Investigational Site Number 250008
🇫🇷Vihiers, France
Investigational Site Number 276005
🇩🇪Berlin, Germany
Investigational Site Number 710006
🇿🇦Parktown, South Africa
Investigational Site Number 710010
🇿🇦Centurion, South Africa
Investigational Site Number 276012
🇩🇪Magdeburg, Germany
Investigational Site Number 376002
🇮🇱Afula, Israel
Investigational Site Number 724006
🇪🇸Córdoba, Spain
Investigational Site Number 710009
🇿🇦Roodepoort, South Africa
Investigational Site Number 752004
🇸🇪Stockholm, Sweden
Investigational Site Number 826008
🇬🇧Liverpool, United Kingdom
Investigational Site Number 724004
🇪🇸Sevilla, Spain
Investigational Site Number 724007
🇪🇸Málaga, Spain
Investigational Site Number 710005
🇿🇦Witbank, South Africa
Investigational Site Number 752006
🇸🇪Stockholm, Sweden
Investigational Site Number 710001
🇿🇦Pretoria, South Africa
Investigational Site Number 826012
🇬🇧Cardiff, United Kingdom
Investigational Site Number 710011
🇿🇦Middelburg, South Africa
Investigational Site Number 724003
🇪🇸Granada, Spain
Investigational Site Number 826004
🇬🇧Addlestone, United Kingdom
Investigational Site Number 710004
🇿🇦Pretoria, South Africa
Investigational Site Number 826006
🇬🇧Chorley, United Kingdom
Investigational Site Number 616010
🇵🇱Katowice, Poland
Investigational Site Number 752002
🇸🇪Rättvik, Sweden
Investigational Site Number 752003
🇸🇪Stockholm, Sweden
Investigational Site Number 826003
🇬🇧Irvine, United Kingdom
Investigational Site Number 724005
🇪🇸Reus, Spain
Investigational Site Number 710007
🇿🇦Worcester, South Africa
Investigational Site Number 710008
🇿🇦Meyerspark, South Africa
Investigational Site Number 724002
🇪🇸Madrid, Spain
Investigational Site Number 804003
🇺🇦Dnipropetrovsk, Ukraine
Investigational Site Number 752001
🇸🇪Örebro, Sweden
Investigational Site Number 826023
🇬🇧Cambridge, United Kingdom
Investigational Site Number 826013
🇬🇧Romford, United Kingdom
Investigational Site Number 710002
🇿🇦Pretoria, South Africa
Investigational Site Number 826007
🇬🇧Manchester, United Kingdom
Investigational Site Number 826010
🇬🇧Glasgow, United Kingdom
Investigational Site Number 826019
🇬🇧Penzance, United Kingdom
Investigational Site Number 826011
🇬🇧Reading, United Kingdom
Investigational Site Number 840221
🇺🇸Miami, Florida, United States
Investigational Site Number 840084
🇺🇸Wichita, Kansas, United States
Investigational Site Number 840068
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 208003
🇩🇰Slagelse, Denmark
Investigational Site Number 208001
🇩🇰Svendborg, Denmark
Investigational Site Number 380006
🇮🇹Chieti, Italy
Investigational Site Number 380002
🇮🇹Cinisello Balsamo, Italy
Investigational Site Number 380001
🇮🇹Palermo, Italy
Investigational Site Number 380005
🇮🇹Pozzilli, Italy
Investigational Site Number 380008
🇮🇹Vittorio Veneto, Italy
Investigational Site Number 380009
🇮🇹Milano, Italy
Investigational Site Number 826016
🇬🇧Birmingham, United Kingdom
Investigational Site Number 826024
🇬🇧Chichester, United Kingdom
Investigational Site Number 826005
🇬🇧Liverpool, United Kingdom
Investigational Site Number 826025
🇬🇧Manchester, United Kingdom
Investigational Site Number 826001
🇬🇧Middlesex, United Kingdom
Investigational Site Number 826014
🇬🇧Soham, United Kingdom
Investigational Site Number 840184
🇺🇸Clearwater, Florida, United States
Investigational Site Number 840039
🇺🇸Clearwater, Florida, United States
Investigational Site Number 840167
🇺🇸Fleming Island, Florida, United States
Investigational Site Number 710003
🇿🇦Somerset West, South Africa
Investigational Site Number 840090
🇺🇸Ft. Lauderdale, Florida, United States
Investigational Site Number 840103
🇺🇸Tucson, Arizona, United States
Investigational Site Number 840065
🇺🇸Tempe, Arizona, United States
Investigational Site Number 840246
🇺🇸Hartford, Connecticut, United States
Investigational Site Number 840055
🇺🇸Stamford, Connecticut, United States
Investigational Site Number 840028
🇺🇸Gilbert, Arizona, United States
Investigational Site Number 840035
🇺🇸Sierra Vista, Arizona, United States
Investigational Site Number 840052
🇺🇸Tempe, Arizona, United States
Investigational Site Number 840079
🇺🇸Tempe, Arizona, United States
Investigational Site Number 840094
🇺🇸Tempe, Arizona, United States
Investigational Site Number 840224
🇺🇸Bridgeport, Connecticut, United States
Investigational Site Number 840134
🇺🇸Guilford, Connecticut, United States
Investigational Site Number 840153
🇺🇸Jacksonville, Florida, United States
Investigational Site Number 100007
🇧🇬Varna, Bulgaria
Investigational Site Number 840105
🇺🇸Varnville, South Carolina, United States
Investigational Site Number 840091
🇺🇸Stamford, Connecticut, United States
Investigational Site Number 840181
🇺🇸Jacksonville, Florida, United States
Investigational Site Number 100005
🇧🇬Sofia, Bulgaria
Investigational Site Number 484010
🇲🇽Df, Mexico
Investigational Site Number 578005
🇳🇴Elverum, Norway
Investigational Site Number 642005
🇷🇴Baia Mare, Romania
Investigational Site Number 804011
🇺🇦Kyiv, Ukraine
Investigational Site Number 804010
🇺🇦Kyiv, Ukraine
Investigational Site Number 170004
🇨🇴Barranquilla, Colombia
Investigational Site Number 840074
🇺🇸Simpsonville, South Carolina, United States
Investigational Site Number 032006
🇦🇷Buenos Aires, Argentina
Investigational Site Number 484003
🇲🇽Xalapa, Mexico
Investigational Site Number 376005
🇮🇱Holon, Israel
Investigational Site Number 484009
🇲🇽Torreon, Mexico
Investigational Site Number 528010
🇳🇱Zoetermeer, Netherlands
Investigational Site Number 578001
🇳🇴Hamar, Norway
Investigational Site Number 578002
🇳🇴Oslo, Norway
Investigational Site Number 616008
🇵🇱Gdynia, Poland
Investigational Site Number 484001
🇲🇽San Luis Potosi, Mexico
Investigational Site Number 840059
🇺🇸Largo, Florida, United States
Investigational Site Number 528013
🇳🇱Amsterdam, Netherlands
Investigational Site Number 528004
🇳🇱Breda, Netherlands
Investigational Site Number 528001
🇳🇱Amsterdam, Netherlands
Investigational Site Number 528005
🇳🇱Eindhoven, Netherlands
Investigational Site Number 616009
🇵🇱Warszawa, Poland
Investigational Site Number 620005
🇵🇹Porto, Portugal
Investigational Site Number 643006
🇷🇺St Petersburg, Russian Federation
Investigational Site Number 643009
🇷🇺St.Petersburg, Russian Federation
Investigational Site Number 804001
🇺🇦Kyiv, Ukraine
Investigational Site Number 804005
🇺🇦Zhytomyr, Ukraine
Investigational Site Number 643008
🇷🇺Moscow, Russian Federation
Investigational Site Number 528007
🇳🇱Groningen, Netherlands
Investigational Site Number 578004
🇳🇴Skedsmokorset, Norway
Investigational Site Number 616018
🇵🇱Krakow, Poland
Investigational Site Number 616004
🇵🇱Piotrkow Trybunalski, Poland
Investigational Site Number 528002
🇳🇱Hoorn, Netherlands
Investigational Site Number 528008
🇳🇱Leiderdorp, Netherlands
Investigational Site Number 528009
🇳🇱Rotterdam, Netherlands
Investigational Site Number 528006
🇳🇱Velp, Netherlands
Investigational Site Number 840021
🇺🇸New Port Richey, Florida, United States
Investigational Site Number 578003
🇳🇴Stavanger, Norway
Investigational Site Number 616003
🇵🇱Gdynia, Poland
Investigational Site Number 616001
🇵🇱Gniewkowo, Poland
Investigational Site Number 616013
🇵🇱Pulawy, Poland
Investigational Site Number 643005
🇷🇺Barnaul, Russian Federation
Investigational Site Number 643004
🇷🇺Yaroslavl, Russian Federation
Investigational Site Number 643012
🇷🇺Moscow, Russian Federation
Investigational Site Number 620006
🇵🇹Funchal / Madeira, Portugal
Investigational Site Number 642002
🇷🇴Brasov, Romania
Investigational Site Number 804008
🇺🇦Kyiv, Ukraine
Investigational Site Number 620002
🇵🇹Lisboa, Portugal
Investigational Site Number 620001
🇵🇹Lisboa, Portugal
Investigational Site Number 642001
🇷🇴Timisoara, Romania
Investigational Site Number 804014
🇺🇦Kharkiv, Ukraine
Investigational Site Number 643014
🇷🇺Perm, Russian Federation
Investigational Site Number 804002
🇺🇦Donetsk, Ukraine
Investigational Site Number 804016
🇺🇦Kiev, Ukraine
Investigational Site Number 804012
🇺🇦Chernivtsi, Ukraine
Investigational Site Number 804013
🇺🇦Kyiv, Ukraine
Investigational Site Number 840122
🇺🇸New Smyrna Beach, Florida, United States
Investigational Site Number 840108
🇺🇸Ormond Beach, Florida, United States
Investigational Site Number 840067
🇺🇸Palm Harbor, Florida, United States
Investigational Site Number 840006
🇺🇸Pembroke Pines, Florida, United States
Investigational Site Number 840001
🇺🇸St. Petersburg, Florida, United States
Investigational Site Number 840117
🇺🇸Cumming, Georgia, United States
Investigational Site Number 840110
🇺🇸Roswell, Georgia, United States
Investigational Site Number 840075
🇺🇸Meridian, Idaho, United States
Investigational Site Number 840027
🇺🇸Evansville, Indiana, United States
Investigational Site Number 840093
🇺🇸Indianapolis, Indiana, United States
Investigational Site Number 840222
🇺🇸Iowa City, Iowa, United States
Investigational Site Number 840165
🇺🇸West Des Moines, Iowa, United States
Investigational Site Number 840200
🇺🇸Kansas City, Kansas, United States
Investigational Site Number 840040
🇺🇸Wichita, Kansas, United States
Investigational Site Number 840061
🇺🇸Wichita, Kansas, United States
Investigational Site Number 840032
🇺🇸Wichita, Kansas, United States
Investigational Site Number 840244
🇺🇸Biddeford, Maine, United States
Investigational Site Number 840158
🇺🇸Framingham, Maine, United States
Investigational Site Number 840193
🇺🇸Novi, Michigan, United States
Investigational Site Number 840162
🇺🇸Saginaw, Michigan, United States
Investigational Site Number 840113
🇺🇸St. Louis, Missouri, United States
Investigational Site Number 840095
🇺🇸Henderson, Nevada, United States
Investigational Site Number 840096
🇺🇸Henderson, Nevada, United States
Investigational Site Number 840022
🇺🇸Edison, New Jersey, United States
Investigational Site Number 840011
🇺🇸Hillsborough, New Jersey, United States
Investigational Site Number 840049
🇺🇸Trenton, New Jersey, United States
Investigational Site Number 840129
🇺🇸Brooklyn, New York, United States
Investigational Site Number 840217
🇺🇸Asheville, North Carolina, United States
Investigational Site Number 840160
🇺🇸Poughkeepsie, New York, United States
Investigational Site Number 840023
🇺🇸Charlotte, North Carolina, United States
Investigational Site Number 840104
🇺🇸Raleigh, North Carolina, United States
Investigational Site Number 840083
🇺🇸Greensboro, North Carolina, United States
Investigational Site Number 840007
🇺🇸Dayton, Ohio, United States
Investigational Site Number 840013
🇺🇸Marion, Ohio, United States
Investigational Site Number 840161
🇺🇸Mentor, Ohio, United States
Investigational Site Number 840170
🇺🇸Beaver, Pennsylvania, United States
Investigational Site Number 840180
🇺🇸Camp Hill, Pennsylvania, United States
Investigational Site Number 840155
🇺🇸Phoenixville, Pennsylvania, United States
Investigational Site Number 840004
🇺🇸Duncansville, Pennsylvania, United States
Investigational Site Number 840177
🇺🇸Scranton, Pennsylvania, United States
Investigational Site Number 840202
🇺🇸Wyomissing, Pennsylvania, United States
Investigational Site Number 840087
🇺🇸Greenville, South Carolina, United States
Investigational Site Number 840190
🇺🇸Knoxville, Tennessee, United States
Investigational Site Number 840058
🇺🇸Fort Worth, Texas, United States
Investigational Site Number 840092
🇺🇸Dallas, Texas, United States
Investigational Site Number 840212
🇺🇸Dallas, Texas, United States
Investigational Site Number 840149
🇺🇸Fort Worth, Texas, United States
Investigational Site Number 840038
🇺🇸Houston, Texas, United States
Investigational Site Number 840072
🇺🇸Sugar Land, Texas, United States
Investigational Site Number 840053
🇺🇸Plano, Texas, United States
Investigational Site Number 840241
🇺🇸Tyler, Texas, United States
Investigational Site Number 840204
🇺🇸Chesapeake, Virginia, United States
Investigational Site Number 840120
🇺🇸Spokane, Washington, United States
Investigational Site Number 840111
🇺🇸Milwaukee, Wisconsin, United States
Investigational Site Number 032001
🇦🇷Coronel Suarez, Argentina
Investigational Site Number 032010
🇦🇷Caba, Argentina
Investigational Site Number 032008
🇦🇷Capital Federal, Argentina
Investigational Site Number 032004
🇦🇷Resistencia, Argentina
Investigational Site Number 056005
🇧🇪Antwerpen, Belgium
Investigational Site Number 056001
🇧🇪Natoye, Belgium
Investigational Site Number 056004
🇧🇪Genk, Belgium
Investigational Site Number 056002
🇧🇪Wetteren, Belgium
Investigational Site Number 100008
🇧🇬Pleven, Bulgaria
Investigational Site Number 100015
🇧🇬Sofia, Bulgaria
Investigational Site Number 100013
🇧🇬Stara Zagora, Bulgaria
Investigational Site Number 100001
🇧🇬Sofia, Bulgaria
Investigational Site Number 840031
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 124002
🇨🇦London, Canada
Investigational Site Number 124001
🇨🇦Hawkesbury, Canada
Investigational Site Number 124009
🇨🇦Mirabel, Canada
Investigational Site Number 124013
🇨🇦Cambridge, Canada
Investigational Site Number 124018
🇨🇦Montreal, Canada
Investigational Site Number 124027
🇨🇦Coquitlam, Canada
Investigational Site Number 124007
🇨🇦Ottawa, Canada
Investigational Site Number 124011
🇨🇦Quebec, Canada
Investigational Site Number 124005
🇨🇦Saint John'S, Canada
Investigational Site Number 124008
🇨🇦Sarnia, Canada
Investigational Site Number 124022
🇨🇦Terrebonne, Canada
Investigational Site Number 124006
🇨🇦Victoria, Canada
Investigational Site Number 124003
🇨🇦Vancouver, Canada
Investigational Site Number 124015
🇨🇦Woodstock, Canada
Investigational Site Number 152008
🇨🇱Santiago, Chile
Investigational Site Number 152006
🇨🇱Santiago, Chile
Investigational Site Number 152004
🇨🇱Temuco, Chile
Investigational Site Number 170005
🇨🇴Barranquilla, Colombia
Investigational Site Number 170008
🇨🇴Barranquilla, Colombia
Investigational Site Number 170001
🇨🇴Manizales, Colombia
Investigational Site Number 170003
🇨🇴Medellin, Colombia
Investigational Site Number 203004
🇨🇿Praha 2, Czech Republic
Investigational Site Number 203006
🇨🇿Praha 5, Czech Republic
Investigational Site Number 208005
🇩🇰Aarhus, Denmark
Investigational Site Number 208004
🇩🇰Hellerup, Denmark
Investigational Site Number 208002
🇩🇰Viborg, Denmark
Investigational Site Number 246002
🇫🇮Joensuu, Finland
Investigational Site Number 250007
🇫🇷Bandol, France
Investigational Site Number 246001
🇫🇮Kokkola, Finland
Investigational Site Number 246004
🇫🇮Vantaa, Finland
Investigational Site Number 246003
🇫🇮Kuopio, Finland
Investigational Site Number 250003
🇫🇷Broglie, France
Investigational Site Number 250014
🇫🇷Bron Cedex, France
Investigational Site Number 250006
🇫🇷Lille Cedex, France
Investigational Site Number 250004
🇫🇷Dijon, France
Investigational Site Number 250009
🇫🇷Nantes, France
Investigational Site Number 250001
🇫🇷Nantes, France
Investigational Site Number 250002
🇫🇷Paris Cedex 13, France
Investigational Site Number 250010
🇫🇷Pessac, France
Investigational Site Number 250005
🇫🇷Vieux Conde, France
Investigational Site Number 250012
🇫🇷Rennes, France
Investigational Site Number 276001
🇩🇪Bad Wörishofen, Germany
Investigational Site Number 276008
🇩🇪Bochum, Germany
Investigational Site Number 276007
🇩🇪Berlin, Germany
Investigational Site Number 276014
🇩🇪Berlin, Germany
Investigational Site Number 276009
🇩🇪Dresden, Germany
Investigational Site Number 276004
🇩🇪Essen, Germany
Investigational Site Number 276010
🇩🇪Frankfurt A.M., Germany
Investigational Site Number 276011
🇩🇪Görlitz, Germany
Investigational Site Number 276019
🇩🇪Hannover, Germany
Investigational Site Number 276013
🇩🇪Leipzig, Germany
Investigational Site Number 348007
🇭🇺Budapest, Hungary
Investigational Site Number 276003
🇩🇪Magdeburg, Germany
Investigational Site Number 276015
🇩🇪Witten, Germany
Investigational Site Number 348003
🇭🇺Baja, Hungary
Investigational Site Number 276006
🇩🇪Schwerin, Germany
Investigational Site Number 348009
🇭🇺Budapest, Hungary
Investigational Site Number 348008
🇭🇺Budapest, Hungary
Investigational Site Number 348004
🇭🇺Debrecen, Hungary
Investigational Site Number 348002
🇭🇺Nagykanizsa, Hungary
Investigational Site Number 348006
🇭🇺Nyiregyhaza, Hungary
Investigational Site Number 348001
🇭🇺Sopron, Hungary
Investigational Site Number 348011
🇭🇺Urhida, Hungary
Investigational Site Number 376003
🇮🇱Holon, Israel
Investigational Site Number 376004
🇮🇱Nazareth, Israel
Investigational Site Number 616007
🇵🇱Wroclaw, Poland
Investigational Site Number 840033
🇺🇸Saint Louis, Missouri, United States
Investigational Site Number 642004
🇷🇴Targu Mures, Romania
Investigational Site Number 826009
🇬🇧Birmingham, United Kingdom
Investigational Site Number 724008
🇪🇸Quart De Poblet, Spain
Investigational Site Number 724001
🇪🇸Sabadell, Spain
Investigational Site Number 826021
🇬🇧Blackpool, United Kingdom
Investigational Site Number 840005
🇺🇸Tulsa, Oklahoma, United States
Investigational Site Number 840097
🇺🇸Bronxville, New York, United States
Investigational Site Number 840018
🇺🇸Fort Lauderdale, Florida, United States
Investigational Site Number 840020
🇺🇸Bradenton, Florida, United States
Investigational Site Number 840166
🇺🇸Daytona Beach, Florida, United States
Investigational Site Number 840026
🇺🇸Savannah, Georgia, United States
Investigational Site Number 840036
🇺🇸West Palm Beach, Florida, United States
Investigational Site Number 840152
🇺🇸Jacksonville, Florida, United States
Investigational Site Number 348013
🇭🇺Budapest, Hungary
Investigational Site Number 840045
🇺🇸Sacramento, California, United States
Investigational Site Number 840073
🇺🇸Charleston, South Carolina, United States
Investigational Site Number 840077
🇺🇸Golden, Colorado, United States
Investigational Site Number 840209
🇺🇸Beverly Hills, California, United States
Investigational Site Number 840041
🇺🇸Brandon, Florida, United States