GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Pioglitazone
- Conditions
- Diabetes Mellitus Type 2
- Interventions
- Registration Number
- NCT00763815
- Lead Sponsor
- Sanofi
- Brief Summary
The purpose of this study is to evaluate the benefits and risks of lixisenatide (AVE0010), in comparison to placebo, as an add-on treatment to pioglitazone with or without metformin, over a period of 24 weeks of treatment, followed by an extension.
The primary objective is to assess the effects of lixisenatide when added to pioglitazone on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.
Secondary objectives are to assess the effects of lixisenatide when added to pioglitazone on the percentage of patients reaching HbA1c less than 7 percent (%) and less than or equal to 6.5%, fasting plasma glucose (FPG), body weight, beta-cell function (assessed by homeostatic model assessment of beta-cell function \[HOMA-beta\]), and on fasting plasma insulin (FPI), to assess the safety, tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development.
- Detailed Description
Patients who complete the 24-week main double-blind treatment would undergo a variable double-blind extension treatment, which ends for all patients at approximately the schedule date of Week 76 visit (Visit 25) for the last randomized patients.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 484
- Type 2 diabetes mellitus, diagnosed for at least 1 year at the time of the screening visit, insufficiently controlled with pioglitazone
- HbA1c less than (<) 7 percent (%) or greater than (>) 10% at screening
- At the time of screening age <legal age of majority
- Pregnant or breastfeeding women and women of childbearing potential without effective contraceptive method of birth control
- Type 1 diabetes mellitus
- Pioglitazone not at a stable dose of at least 30 milligram per day (mg/day) for at least 3 months prior to screening
- If treatment with metformin, no stable dose of at least 1.5 gram per day (g/day) for at least 3 months prior to screening visit
- FPG at screening >250 milligram per deciliter (mg/dL) (>13.9 millimole per liter [mmol/L])
- Body mass index less than or equal to (<=) 20 kilogram per square meter (kg/m^2)
- Weight change of more than 5 kg during the 3 months preceding the screening visit
- History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, or inflammatory bowel disease
- History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
- Hemoglobinopathy or hemolytic anemia, or receipt of blood or plasma products within3 months prior to the time of screening
- History of myocardial infarction or stroke within the last 6 months prior to screening
- Known history of drug or alcohol abuse within 6 months prior to the time of screening
- Cardiovascular, hepatic, neurological, endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period
- Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic blood pressure or diastolic blood pressure (DBP) >180 millimeter of mercury (mmHg) or >95 mmHg, respectively
- Laboratory findings at the time of screening: aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP): >2 times upper limit of normal (ULN) laboratory range; amylase and/or lipase: >3 times ULN; total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome); Hemoglobin <11 gram/deciliter and/or neutrophils <1500 per cubic millimeter (mm^3) and/or platelets <100 000/mm^3; positive test for Hepatitis B surface antigen (HBsAg) and/or Hepatitis C antibody (HCAb); positive serum pregnancy test in females of childbearing potential
- Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram (ECG), or vital signs at the time of screening that, in the judgment of the investigator or any sub-investigator, precludes safe completion of the study or constrains efficacy assessment
- Patients who are considered by the investigator or any sub-investigator as inappropriate for this study for any reason (for example, impossibility to meet specific protocol requirements [such as scheduled visits, being able to do self-injections]; likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol; investigator or any sub-investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol)
- Use of other oral or injectable antidiabetic or hypoglycemic agents other than metformin or pioglitazone (for example, sulfonylurea, alpha-glucosidase inhibitor, other thiazolidinediones, rimonabant, exenatide, dipeptidyl peptidase-4 [DPP-4] inhibitors, insulin) within 3 months prior to the time of screening
- Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to the time of screening
- Use of any investigational drug within 3 months prior to study
- Any previous treatment with lixisenatide or participation in a previous study with lixisenatide
- Renal impairment defined with creatinine >1.4 mg/dL in women and creatinine >1.5 mg/dL in men (applicable only for patients with metformin treatment)
- Patients with cardiac failure or history of cardiac failure (New York Heart Association class I to IV)
- End-stage renal disease defined by a serum creatinine clearance of <15 milliliter per minute (mL/min) (calculated by the Cockcroft and Gault formula) and/or patients on dialysis, if no treatment with metformin
- Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to, gastroparesis and gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening
- Allergic reaction to any glucagon like peptide-1 (GLP-1) agonist in the past (for example,exenatide, liraglutide) or to metacresol
- Additional exclusion criteria at the end of the run-in phase: informed consent withdrawal; lack of compliance during the single-blind placebo run-in phase (>2 injections missed); and patient with any adverse event which precludes the inclusion in the study, as assessed by the investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lixisenatide Pen auto-injector 2-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment. Lixisenatide Lixisenatide (AVE0010) 2-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment. Lixisenatide Pioglitazone 2-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment. Lixisenatide Metformin 2-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment. Placebo Placebo 2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment. Placebo Pen auto-injector 2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment. Placebo Pioglitazone 2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment. Placebo Metformin 2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment.
- Primary Outcome Measures
Name Time Method Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 Baseline, Week 24 Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 Baseline, Week 24 Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Change From Baseline in Body Weight at Week 24 Baseline, Week 24 Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Change From Baseline in Fasting Plasma Insulin (FPI) at Week 24 Baseline, Week 24 Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24 Week 24 The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Percentage of Patients With HbA1c Level Less Than or Equal to 6.5% at Week 24 Week 24 The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Change From Baseline in Beta-cell Function Assessed by Homeostasis Model Assessment for Beta-cell Function (HOMA-beta) at Week 24 Baseline, Week 24 Beta cell function was assessed by HOMA-beta. HOMA-beta (% of normal beta cells function) = (20 multiplied by fasting plasma insulin \[micro unit per milliliter\]) divided by (fasting plasma glucose \[mmol/L\] minus 3.5). Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period Baseline up to Week 24 Routine fasting self-monitored plasma glucose (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) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG \>270 milligram/deciliter (mg/dL) (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG \>240 mg/dL (13.3 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8.5%. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Trial Locations
- Locations (150)
Sanofi-Aventis Investigational Site Number 840708
🇺🇸Kalamazoo, Michigan, United States
Sanofi-Aventis Investigational Site Number 840792
🇺🇸Columbia, South Carolina, United States
Sanofi-Aventis Investigational Site Number 840855
🇺🇸Mobile, Alabama, United States
Sanofi-Aventis Investigational Site Number 840784
🇺🇸Los Banos, California, United States
Sanofi-Aventis Investigational Site Number 840863
🇺🇸Mobile, Alabama, United States
Sanofi-Aventis Investigational Site Number 840722
🇺🇸Mesa, Arizona, United States
Sanofi-Aventis Investigational Site Number 840795
🇺🇸Artesia, California, United States
Sanofi-Aventis Investigational Site Number 840858
🇺🇸La Jolla, California, United States
Sanofi-Aventis Investigational Site Number 840767
🇺🇸Kansas City, Kansas, United States
Sanofi-Aventis Investigational Site Number 840799
🇺🇸Wellington, Florida, United States
Sanofi-Aventis Investigational Site Number 840765
🇺🇸St Louis, Missouri, United States
Sanofi-Aventis Investigational Site Number 840872
🇺🇸Colorado Springs, Colorado, United States
Sanofi-Aventis Investigational Site Number 840727
🇺🇸Jacksonville, Florida, United States
Sanofi-Aventis Investigational Site Number 840785
🇺🇸Huntington Beach, California, United States
Sanofi-Aventis Investigational Site Number 840763
🇺🇸West Hills, California, United States
Sanofi-Aventis Investigational Site Number 840766
🇺🇸New York City, New York, United States
Sanofi-Aventis Investigational Site Number 840868
🇺🇸Colorado Springs, Colorado, United States
Sanofi-Aventis Investigational Site Number 840850
🇺🇸Lexington, Kentucky, United States
Sanofi-Aventis Investigational Site Number 840857
🇺🇸Augusta, Georgia, United States
Sanofi-Aventis Investigational Site Number 840712
🇺🇸High Point, North Carolina, United States
Sanofi-Aventis Investigational Site Number 840879
🇺🇸Shreveport, Louisiana, United States
Sanofi-Aventis Investigational Site Number 840782
🇺🇸Chino, California, United States
Sanofi-Aventis Investigational Site Number 840745
🇺🇸New Port Richey, Florida, United States
Sanofi-Aventis Investigational Site Number 840726
🇺🇸Taylors, South Carolina, United States
Sanofi-Aventis Investigational Site Number 840701
🇺🇸Medford, Oregon, United States
Sanofi-Aventis Investigational Site Number 840789
🇺🇸Lexington, Kentucky, United States
Sanofi-Aventis Investigational Site Number 840864
🇺🇸Roseville, California, United States
Sanofi-Aventis Investigational Site Number 840877
🇺🇸Fargo, North Dakota, United States
Sanofi-Aventis Investigational Site Number 840707
🇺🇸Mission Viejo, California, United States
Sanofi-Aventis Investigational Site Number 840743
🇺🇸San Mateo, California, United States
Sanofi-Aventis Investigational Site Number 840761
🇺🇸Oviedo, Florida, United States
Sanofi-Aventis Investigational Site Number 040705
🇦🇹Wien, Austria
Sanofi-Aventis Investigational Site Number 124716
🇨🇦Sudbury, Canada
Sanofi-Aventis Investigational Site Number 840862
🇺🇸Baton Rouge, Louisiana, United States
Sanofi-Aventis Investigational Site Number 840760
🇺🇸Greensboro, North Carolina, United States
Sanofi-Aventis Investigational Site Number 840739
🇺🇸Wichita, Kansas, United States
Sanofi-Aventis Investigational Site Number 124712
🇨🇦Mirabel, Canada
Sanofi-Aventis Investigational Site Number 840704
🇺🇸Eagan, Minnesota, United States
Sanofi-Aventis Investigational Site Number 840866
🇺🇸Pahrump, Nevada, United States
Sanofi-Aventis Investigational Site Number 840777
🇺🇸Athens, Ohio, United States
Sanofi-Aventis Investigational Site Number 840740
🇺🇸Simpsonville, South Carolina, United States
Sanofi-Aventis Investigational Site Number 840796
🇺🇸Clinton, Utah, United States
Sanofi-Aventis Investigational Site Number 840716
🇺🇸Norman, Oklahoma, United States
Sanofi-Aventis Investigational Site Number 840853
🇺🇸Colleyville, Texas, United States
Sanofi-Aventis Investigational Site Number 040707
🇦🇹Wels, Austria
Sanofi-Aventis Investigational Site Number 840770
🇺🇸Norfolk, Virginia, United States
Sanofi-Aventis Investigational Site Number 040701
🇦🇹Wien, Austria
Sanofi-Aventis Investigational Site Number 124705
🇨🇦St-Romuald, Canada
Sanofi-Aventis Investigational Site Number 840711
🇺🇸Bristol, Tennessee, United States
Sanofi-Aventis Investigational Site Number 124701
🇨🇦Thornhill, Canada
Sanofi-Aventis Investigational Site Number 250701
🇫🇷Strasbourg, France
Sanofi-Aventis Investigational Site Number 040704
🇦🇹Vienna, Austria
Sanofi-Aventis Investigational Site Number 840751
🇺🇸Beaver, Pennsylvania, United States
Sanofi-Aventis Investigational Site Number 276708
🇩🇪Asslar, Germany
Sanofi-Aventis Investigational Site Number 124710
🇨🇦London, Canada
Sanofi-Aventis Investigational Site Number 124711
🇨🇦Sherbrooke, Canada
Sanofi-Aventis Investigational Site Number 840757
🇺🇸Virginia Beach, Virginia, United States
Sanofi-Aventis Investigational Site Number 040706
🇦🇹Graz, Austria
Sanofi-Aventis Investigational Site Number 124708
🇨🇦Vancouver, Canada
Sanofi-Aventis Investigational Site Number 276701
🇩🇪Würzburg, Germany
Sanofi-Aventis Investigational Site Number 124703
🇨🇦Saskatoon, Canada
Sanofi-Aventis Investigational Site Number 250702
🇫🇷Le Creusot, France
Sanofi-Aventis Investigational Site Number 124713
🇨🇦Scarborough, Canada
Sanofi-Aventis Investigational Site Number 124704
🇨🇦Smiths Falls, Canada
Sanofi-Aventis Investigational Site Number 250707
🇫🇷La Rochelle Cedex, France
Sanofi-Aventis Investigational Site Number 642710
🇷🇴Timisoara, Romania
Sanofi-Aventis Investigational Site Number 840791
🇺🇸Chicago, Illinois, United States
Sanofi-Aventis Investigational Site Number 840794
🇺🇸Indianapolis, Indiana, United States
Sanofi-Aventis Investigational Site Number 840730
🇺🇸Houston, Texas, United States
Sanofi-Aventis Investigational Site Number 840871
🇺🇸Rockville, Maryland, United States
Sanofi-Aventis Investigational Site Number 840764
🇺🇸Hyattsville, Maryland, United States
Sanofi-Aventis Investigational Site Number 840772
🇺🇸San Diego, California, United States
Sanofi-Aventis Investigational Site Number 840755
🇺🇸Salt Lake City, Utah, United States
Sanofi-Aventis Investigational Site Number 840756
🇺🇸Salt Lake City, Utah, United States
Sanofi-Aventis Investigational Site Number 840758
🇺🇸Salt Lake City, Utah, United States
Sanofi-Aventis Investigational Site Number 840744
🇺🇸Birmingham, Alabama, United States
Sanofi-Aventis Investigational Site Number 840723
🇺🇸Birmingham, Alabama, United States
Sanofi-Aventis Investigational Site Number 840867
🇺🇸Birmingham, Alabama, United States
Sanofi-Aventis Investigational Site Number 840769
🇺🇸Phoenix, Arizona, United States
Sanofi-Aventis Investigational Site Number 840720
🇺🇸Birmingham, Alabama, United States
Sanofi-Aventis Investigational Site Number 276703
🇩🇪Künzing, Germany
Sanofi-Aventis Investigational Site Number 276706
🇩🇪Leipzig, Germany
Sanofi-Aventis Investigational Site Number 276704
🇩🇪Berlin, Germany
Sanofi-Aventis Investigational Site Number 840775
🇺🇸Chandler, Arizona, United States
Sanofi-Aventis Investigational Site Number 840729
🇺🇸Harrisburg, Arkansas, United States
Sanofi-Aventis Investigational Site Number 840773
🇺🇸Mission Hills, California, United States
Sanofi-Aventis Investigational Site Number 840776
🇺🇸Mountain Home, Arkansas, United States
Sanofi-Aventis Investigational Site Number 840721
🇺🇸Stockton, California, United States
Sanofi-Aventis Investigational Site Number 840724
🇺🇸Idaho Falls, Idaho, United States
Sanofi-Aventis Investigational Site Number 840738
🇺🇸Avon, Indiana, United States
Sanofi-Aventis Investigational Site Number 840779
🇺🇸Lansing, Kansas, United States
Sanofi-Aventis Investigational Site Number 840851
🇺🇸Dartmouth, Massachusetts, United States
Sanofi-Aventis Investigational Site Number 840874
🇺🇸Staten Island, New York, United States
Sanofi-Aventis Investigational Site Number 840865
🇺🇸New York, New York, United States
Sanofi-Aventis Investigational Site Number 840762
🇺🇸West Seneca, New York, United States
Sanofi-Aventis Investigational Site Number 840875
🇺🇸Las Vegas, Nevada, United States
Sanofi-Aventis Investigational Site Number 840747
🇺🇸Burlington, North Carolina, United States
Sanofi-Aventis Investigational Site Number 840780
🇺🇸Bismarck, North Dakota, United States
Sanofi-Aventis Investigational Site Number 840728
🇺🇸Dayton, Ohio, United States
Sanofi-Aventis Investigational Site Number 840798
🇺🇸Red Lion, Pennsylvania, United States
Sanofi-Aventis Investigational Site Number 840854
🇺🇸San Antonio, Texas, United States
Sanofi-Aventis Investigational Site Number 840753
🇺🇸Norfolk, Virginia, United States
Sanofi-Aventis Investigational Site Number 040702
🇦🇹Wien, Austria
Sanofi-Aventis Investigational Site Number 250704
🇫🇷Armentieres, France
Sanofi-Aventis Investigational Site Number 250705
🇫🇷Labarthe Sur Leze, France
Sanofi-Aventis Investigational Site Number 300701
🇬🇷Thessaloniki, Greece
Sanofi-Aventis Investigational Site Number 300705
🇬🇷Athens, Greece
Sanofi-Aventis Investigational Site Number 300704
🇬🇷Athens, Greece
Sanofi-Aventis Investigational Site Number 300703
🇬🇷Athens, Greece
Sanofi-Aventis Investigational Site Number 320701
🇬🇹Guatemala, Guatemala
Sanofi-Aventis Investigational Site Number 320703
🇬🇹Guatemala, Guatemala
Sanofi-Aventis Investigational Site Number 320704
🇬🇹Guatemala, Guatemala
Sanofi-Aventis Investigational Site Number 356703
🇮🇳Bangalore, India
Sanofi-Aventis Investigational Site Number 356702
🇮🇳Hyderabad, India
Sanofi-Aventis Investigational Site Number 484703
🇲🇽Merida, Mexico
Sanofi-Aventis Investigational Site Number 356704
🇮🇳Nagpur, India
Sanofi-Aventis Investigational Site Number 484704
🇲🇽Zapopan, Mexico
Sanofi-Aventis Investigational Site Number 484701
🇲🇽Tlalnepantla, Mexico
Sanofi-Aventis Investigational Site Number 604701
🇵🇪Lima, Peru
Sanofi-Aventis Investigational Site Number 604702
🇵🇪Lima, Peru
Sanofi-Aventis Investigational Site Number 604705
🇵🇪Lima, Peru
Sanofi-Aventis Investigational Site Number 630714
🇵🇷Carolina, Puerto Rico
Sanofi-Aventis Investigational Site Number 630715
🇵🇷Carolina, Puerto Rico
Sanofi-Aventis Investigational Site Number 642711
🇷🇴Alba Iulia, Romania
Sanofi-Aventis Investigational Site Number 642702
🇷🇴Bacau, Romania
Sanofi-Aventis Investigational Site Number 642709
🇷🇴Baia Mare, Romania
Sanofi-Aventis Investigational Site Number 642712
🇷🇴Bucuresti, Romania
Sanofi-Aventis Investigational Site Number 642707
🇷🇴Galati, Romania
Sanofi-Aventis Investigational Site Number 642714
🇷🇴Bucuresti, Romania
Sanofi-Aventis Investigational Site Number 642705
🇷🇴Constanta, Romania
Sanofi-Aventis Investigational Site Number 642703
🇷🇴Ploiesti, Romania
Sanofi-Aventis Investigational Site Number 642706
🇷🇴Targu Mures, Romania
Sanofi-Aventis Investigational Site Number 642713
🇷🇴Resita, Romania
Sanofi-Aventis Investigational Site Number 642715
🇷🇴Timisoara, Romania
Sanofi-Aventis Investigational Site Number 792702
🇹🇷Erzurum, Turkey
Sanofi-Aventis Investigational Site Number 792705
🇹🇷Istanbul, Turkey
Sanofi-Aventis Investigational Site Number 840733
🇺🇸Northridge, California, United States
Sanofi-Aventis Investigational Site Number 276707
🇩🇪Pirna, Germany
Sanofi-Aventis Investigational Site Number 276702
🇩🇪Sulzbach-Rosenberg, Germany
Sanofi-Aventis Investigational Site Number 840741
🇺🇸Cleveland, Ohio, United States
Sanofi-Aventis Investigational Site Number 840774
🇺🇸Bloomington, Minnesota, United States
Sanofi-Aventis Investigational Site Number 840735
🇺🇸Spokane, Washington, United States
Sanofi-Aventis Investigational Site Number 320702
🇬🇹Guatemala, Guatemala
Sanofi-Aventis Investigational Site Number 604703
🇵🇪Lima, Peru
Sanofi-Aventis Investigational Site Number 642701
🇷🇴Brasov, Romania
Sanofi-Aventis Investigational Site Number 356701
🇮🇳Bangalore, India
Sanofi-Aventis Investigational Site Number 642708
🇷🇴Satu Mare, Romania
Sanofi-Aventis Investigational Site Number 840752
🇺🇸Richmond, Virginia, United States
Sanofi-Aventis Investigational Site Number 840717
🇺🇸Picayune, Mississippi, United States
Sanofi-Aventis Investigational Site Number 840709
🇺🇸Mentor, Ohio, United States