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 (LixiLan-O)

A Randomized, 30 Week, Active-controlled, Open-label, 3-treatment Arm, Parallel-group Multicenter Study Comparing the Efficacy and Safety of Insulin Glargine/ Lixisenatide Fixed Ratio Combination to Insulin Glargine Alone and to Lixisenatide Alone on Top of Metformin in Patients With Type 2 Diabetes Mellitus (T2DM)

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Insulin glargine/lixisenatide Fixed Ratio Combination; Drug: Metformin; Drug: Insulin glargine (HOE901); Drug: Lixisenatide (AVE0010)

Detailed Description

Approximately 37 weeks including up to 6 weeks of screening, 30-week treatment period, and a 3 days follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 1170
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
    • Investigational Site Number 036005
  • Camperdown, Australia, 2050
    • Investigational Site Number 036001
  • Kippa Ring, Australia, 4021
    • Investigational Site Number 036006
  • Logan Central, Australia, 4114
    • Investigational Site Number 036007
• Belgium
  • Brussel, Belgium, 1090
    • Investigational Site Number 056006
  • Brussels, Belgium, 1070
    • Investigational Site Number 056005
  • Leuven, Belgium, 3000
    • Investigational Site Number 056001
• Canada
  • Kelowna, Canada, V1Y 1Z9
    • Investigational Site Number 124004
  • Toronto, Canada, M4G 3E8
    • Investigational Site Number 124001
  • Vancouver, Canada, V5Z 1M9
    • Investigational Site Number 124002
• Chile
  • Osorno, Chile, 5311092
    • Investigational Site Number 152008
  • Puerto Varas, Chile
    • Investigational Site Number 152015
  • Santiago, Chile, 7500010
    • Investigational Site Number 152004
  • Santiago, Chile, 7500010
    • Investigational Site Number 152006
  • Santiago, Chile, 7591047
    • Investigational Site Number 152001
  • Santiago, Chile, 7980378
    • Investigational Site Number 152002
  • Santiago, Chile, 8053095
    • Investigational Site Number 152012
  • Santiago, Chile, 8330008
    • Investigational Site Number 152009
  • Talagante, Chile
    • Investigational Site Number 152011
  • Temuco, Chile, 4781156
    • Investigational Site Number 152014
  • Temuco, Chile, 4813299
    • Investigational Site Number 152003
• Czech Republic
  • Beroun, Czech Republic, 26601
    • Investigational Site Number 203004
  • Ceske Budejovice, Czech Republic, 370 01
    • Investigational Site Number 203008
  • Horovice, Czech Republic, 26801
    • Investigational Site Number 203014
  • Koprivnice, Czech Republic, 742 21
    • Investigational Site Number 203012
  • Pardubice, Czech Republic, 53002
    • Investigational Site Number 203001
  • Plzen, Czech Republic, 32600
    • Investigational Site Number 203005
  • Praha 10, Czech Republic, 100 00
    • Investigational Site Number 203003
  • Praha 2, Czech Republic, 12808
    • Investigational Site Number 203009
  • Praha 5, Czech Republic, 15000
    • Investigational Site Number 203007
  • Praha 9 - Klanovice, Czech Republic, 19014
    • Investigational Site Number 203013
  • Trutnov, Czech Republic, 54101
    • Investigational Site Number 203006
  • Ujezd U Brna, Czech Republic
    • Investigational Site Number 203016
  • Vsetin, Czech Republic, 75501
    • Investigational Site Number 203015
• Denmark
  • Aarhus C, Denmark, 8000
    • Investigational Site Number 208003
  • Horsens, Denmark, 8700
    • Investigational Site Number 208009
  • Kolding, Denmark, 6000
    • Investigational Site Number 208002
  • København Nv, Denmark, 2400
    • Investigational Site Number 208001
  • København S, Denmark, 2300
    • Investigational Site Number 208005
  • Viborg, Denmark, 8800
    • Investigational Site Number 208004
• Estonia
  • Paide, Estonia, 72713
    • Investigational Site Number 233004
  • Pärnu, Estonia, 80018
    • Investigational Site Number 233002
  • Tallinn, Estonia, 13415
    • Investigational Site Number 233003
  • Viljandimaa, Estonia, 71024
    • Investigational Site Number 233001
• France
  • Corbeil Essonnes, France, 91109
    • Investigational Site Number 250006
  • La Rochelle Cedex, France, 17019
    • Investigational Site Number 250002
  • Pierre Benite, France, 69310
    • Investigational Site Number 250003
  • Venissieux, France, 69200
    • Investigational Site Number 250001
• Germany
  • Berlin, Germany, 10115
    • Investigational Site Number 276005
  • Berlin, Germany, 13125
    • Investigational Site Number 276003
  • Dortmund, Germany, 44137
    • Investigational Site Number 276004
  • Dresden, Germany, 01069
    • Investigational Site Number 276007
  • Dresden, Germany, 01307
    • Investigational Site Number 276001
  • Hamburg, Germany, 20253
    • Investigational Site Number 276006
  • Neumünster, Germany, 24534
    • Investigational Site Number 276002
• Hungary
  • Balatonfüred, Hungary, 8230
    • Investigational Site Number 348003
  • Budapest, Hungary, 1036
    • Investigational Site Number 348007
  • Budapest, Hungary, 1096
    • Investigational Site Number 348006
  • Budapest, Hungary, 1138
    • Investigational Site Number 348002
  • Komárom, Hungary, 2900
    • Investigational Site Number 348011
  • Nagykanizsa, Hungary, 8800
    • Investigational Site Number 348008
  • Szeged, Hungary, 6720
    • Investigational Site Number 348004
  • Szekesfehervar, Hungary, 8000
    • Investigational Site Number 348010
  • Sátoraljaújhely, Hungary, 3980
    • Investigational Site Number 348012
  • Zalaegerszeg, Hungary, 8900
    • Investigational Site Number 348001
• Italy
  • Bologna, Italy, 40138
    • Investigational Site Number 380002
  • Catanzaro, Italy, 88100
    • Investigational Site Number 380006
  • Milano, Italy, 20132
    • Investigational Site Number 380001
  • Napoli, Italy, 80131
    • Investigational Site Number 380003
  • Roma, Italy, 00133
    • Investigational Site Number 380005
• Latvia
  • Riga, Latvia, LV-1050
    • Investigational Site Number 428004
  • Riga, Latvia, LV-1011
    • Investigational Site Number 428002
  • Riga, Latvia, LV-1011
    • Investigational Site Number 428003
  • Sigulda, Latvia, LV-2150
    • Investigational Site Number 428001
• Lithuania
  • Jonava, Lithuania, LT-55201
    • Investigational Site Number 440003
  • Kaunas, Lithuania, LT-49456
    • Investigational Site Number 440002
  • Kaunas, Lithuania, LT-50009
    • Investigational Site Number 440007
  • Kedainiai, Lithuania, LT-57164
    • Investigational Site Number 440004
  • Panevezys, Lithuania, LT-37355
    • Investigational Site Number 440006
  • Utena, Lithuania, LT-28151
    • Investigational Site Number 440005
  • Vilnius, Lithuania, LT-10323
    • Investigational Site Number 440001
• Mexico
  • Aguascalientes, Mexico, 20230
    • Investigational Site Number 484005
  • Cuernavaca, Mexico, 62250
    • Investigational Site Number 484001
  • Guadalajara, Mexico, 44130
    • Investigational Site Number 484002
  • Guadalajara, Mexico, 44210
    • Investigational Site Number 484004
  • Guadalajara, Mexico, 44670
    • Investigational Site Number 484009
  • Monterrey, Mexico, 64020
    • Investigational Site Number 484007
  • Monterrey, Mexico, 64460
    • Investigational Site Number 484006
  • Zapopan, Mexico, 45116
    • Investigational Site Number 484010
• Poland
  • Bialystok, Poland, 15-435
    • Investigational Site Number 616002
  • Krakow, Poland, 31-261
    • Investigational Site Number 616005
  • Krakow, Poland, 31-548
    • Investigational Site Number 616006
  • Lodz, Poland, 94-074
    • Investigational Site Number 616007
  • Szczecin, Poland, 70-506
    • Investigational Site Number 616004
  • Warszawa, Poland, 01-518
    • Investigational Site Number 616003
  • Warszawa, Poland, 02-507
    • Investigational Site Number 616001
  • Zory, Poland, 44-240
    • Investigational Site Number 616008
• Romania
  • Bucharest, Romania, 010825
    • Investigational Site Number 642008
  • Bucuresti, Romania, 020475
    • Investigational Site Number 642007
  • Cluj Napoca, Romania, 400006
    • Investigational Site Number 642009
  • Hunedoara, Romania, 331057
    • Investigational Site Number 642006
  • Iasi, Romania, 700547
    • Investigational Site Number 642005
  • Oradea, Romania, 410169
    • Investigational Site Number 642002
  • Targu Mures, Romania, 540142
    • Investigational Site Number 642001
  • Timisoara, Romania, 300133
    • Investigational Site Number 642004
  • Timisoara, Romania, 300456
    • Investigational Site Number 642003
• Russian Federation
  • Moscow, Russian Federation, 119991
    • Investigational Site Number 643006
  • Penza, Russian Federation, 440026
    • Investigational Site Number 643008
  • Petrozavodsk, Russian Federation, 185019
    • Investigational Site Number 643012
  • Saint-Petersburg, Russian Federation, 190013
    • Investigational Site Number 643001
  • Samara, Russian Federation, 443067
    • Investigational Site Number 643014
  • Saratov, Russian Federation, 410053
    • Investigational Site Number 643011
  • Saratov, Russian Federation, 410026
    • Investigational Site Number 643009
  • St-Petersburg, Russian Federation, 190068
    • Investigational Site Number 643005
  • St-Petersburg, Russian Federation, 194354
    • Investigational Site Number 643007
  • St-Petersburg, Russian Federation, 195257
    • Investigational Site Number 643002
  • St. Petersburg, Russian Federation, 194358
    • Investigational Site Number 643003
  • Tomsk, Russian Federation, 634050
    • Investigational Site Number 643016
  • Voronezh, Russian Federation, 394018
    • Investigational Site Number 643004
• South Africa
  • Cap Town, South Africa, 7530
    • Investigational Site Number 710002
  • Cape Town, South Africa, 7500
    • Investigational Site Number 710003
  • Meyerspark, South Africa, 0184
    • Investigational Site Number 710005
  • Port Elizabeth, South Africa
    • Investigational Site Number 710007
  • Pretoria, South Africa, 0122
    • Investigational Site Number 710004
  • Somerset West, South Africa, 7130
    • Investigational Site Number 710001
  • Soweto, South Africa, 4309
    • Investigational Site Number 710006
• Spain
  • Barcelona, Spain, 08003
    • Investigational Site Number 724012
  • Granada, Spain, 18012
    • Investigational Site Number 724009
  • Hostalets De Balenyà, Spain, 08550
    • Investigational Site Number 724004
  • La Coruña, Spain, 15006
    • Investigational Site Number 724011
  • Lugo, Spain, 27004
    • Investigational Site Number 724007
  • Madrid, Spain, 28034
    • Investigational Site Number 724008
  • Madrid, Spain, 28046
    • Investigational Site Number 724005
  • Palma De Mallorca, Spain, 07010
    • Investigational Site Number 724013
  • Quart De Poblet, Spain, 46930
    • Investigational Site Number 724001
  • Sant Joan Despí, Spain, 08970
    • Investigational Site Number 724006
  • Sevilla, Spain, 41010
    • Investigational Site Number 724003
• Sweden
  • Ljungby, Sweden, 341 82
    • Investigational Site Number 752001
  • Malmö, Sweden, 211 52
    • Investigational Site Number 752003
  • Rättvik, Sweden, 79530
    • Investigational Site Number 752004
  • Stockholm, Sweden, 11526
    • Investigational Site Number 752005
  • Vällingby, Sweden, 16268
    • Investigational Site Number 752002
• Ukraine
  • Chernivtsi, Ukraine, 58022
    • Investigational Site Number 804002
  • Ivano-Frankovsk, Ukraine, 76008
    • Investigational Site Number 804009
  • Kyiv, Ukraine, 03049
    • Investigational Site Number 804010
  • Kyiv, Ukraine, 04050
    • Investigational Site Number 804007
  • Kyiv, Ukraine
    • Investigational Site Number 804006
  • Lviv, Ukraine, 79010
    • Investigational Site Number 804012
  • Vinnytsya, Ukraine, 21001
    • Investigational Site Number 804011
  • Vinnytsya, Ukraine, 21010
    • Investigational Site Number 804008
• United Kingdom
  • Coventry, United Kingdom, CV2 2DX
    • Investigational Site Number 826001
  • Dundee, United Kingdom, DD1 9SI
    • Investigational Site Number 826002
  • Guildford, United Kingdom, GU2 7XX
    • Investigational Site Number 826006
  • Leicester, United Kingdom, LE5 4PW
    • Investigational Site Number 826007
  • Norwich, United Kingdom, NR1 3SR
    • Investigational Site Number 826003
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85028
      • Investigational Site Number 840027
    • Phoenix, Arizona, United States, 85032
      • Investigational Site Number 840122
    • Tempe, Arizona, United States, 85282
      • Investigational Site Number 840062
    • Tempe, Arizona, United States
      • Investigational Site Number 840023
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Investigational Site Number 840084
  • California
    • Anaheim, California, United States, 92801
      • Investigational Site Number 840100
    • Bell Gardens, California, United States, 90201
      • Investigational Site Number 840065
    • Chino, California, United States, 91710
      • Investigational Site Number 840090
    • Chula Vista, California, United States, 91911
      • Investigational Site Number 840002
    • Concord, California, United States, 94520
      • Investigational Site Number 840013
    • Fresno, California, United States, 93720
      • Investigational Site Number 840053
    • La Jolla, California, United States, 92037
      • Investigational Site Number 840017
    • Lancaster, California, United States, 93534
      • Investigational Site Number 840070
    • Long Beach, California, United States, 90806
      • Investigational Site Number 840121
    • Los Angeles, California, United States, 90017
      • Investigational Site Number 840126
    • Los Angeles, California, United States, 90057
      • Investigational Site Number 840044
    • Mission Hills, California, United States, 91345
      • Investigational Site Number 840101
    • Mission Viejo, California, United States, 92691
      • Investigational Site Number 840086
    • Mission Viejo, California, United States, 92691
      • Investigational Site Number 840120
    • Northridge, California, United States, 91325
      • Investigational Site Number 840005
    • Palm Springs, California, United States, 92262
      • Investigational Site Number 840034
    • Port Hueneme, California, United States, 93041
      • Investigational Site Number 840074
    • San Ramon, California, United States, 94583
      • Investigational Site Number 840068
    • Santa Ana, California, United States, 92704
      • Investigational Site Number 840067
    • Tarzana, California, United States, 91356
      • Investigational Site Number 840029
    • Temecula, California, United States, 92591
      • Investigational Site Number 840006
    • West Hills, California, United States, 91345
      • Investigational Site Number 840078
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Investigational Site Number 840059
    • Denver, Colorado, United States, 80246
      • Investigational Site Number 840038
  • Florida
    • Bradenton, Florida, United States, 34208
      • Investigational Site Number 840104
    • Miami, Florida, United States, 33156-7563
      • Investigational Site Number 840098
    • New Port Richey, Florida, United States, 34652
      • Investigational Site Number 840014
    • Ocoee, Florida, United States, 34761
      • Investigational Site Number 840047
    • Palm Harbor, Florida, United States, 34684
      • Investigational Site Number 840056
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Investigational Site Number 840089
    • Lawrenceville, Georgia, United States, 30046
      • Investigational Site Number 840054
    • Woodstock, Georgia, United States, 30189
      • Investigational Site Number 840119
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Investigational Site Number 840108
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Investigational Site Number 840075
    • Chicago, Illinois, United States, 60607
      • Investigational Site Number 840080
    • Chicago, Illinois, United States, 60612
      • Investigational Site Number 840026
    • Chicago, Illinois, United States, 60616
      • Investigational Site Number 840116
    • Springfield, Illinois, United States, 62704
      • Investigational Site Number 840050
  • Indiana
    • Avon, Indiana, United States, 46123
      • Investigational Site Number 840008
    • Avon, Indiana, United States, 46123
      • Investigational Site Number 840015
    • Avon, Indiana, United States, 46123
      • Investigational Site Number 840076
    • Evansville, Indiana, United States, 47713
      • Investigational Site Number 840082
    • Evansville, Indiana, United States, 47714
      • Investigational Site Number 840031
    • Evansville, Indiana, United States, 47714
      • Investigational Site Number 840060
    • Indianapolis, Indiana, United States, 46202
      • Investigational Site Number 840048
    • Indianapolis, Indiana, United States, 46260
      • Investigational Site Number 840085
    • Valparaiso, Indiana, United States
      • Investigational Site Number 840012
  • Iowa
    • Waterloo, Iowa, United States, 50702
      • Investigational Site Number 840025
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Investigational Site Number 840022
    • Louisville, Kentucky, United States, 40213
      • Investigational Site Number 840007
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Investigational Site Number 840081
  • Maine
    • Auburn, Maine, United States, 04210
      • Investigational Site Number 840097
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Investigational Site Number 840063
  • Michigan
    • Bloomfield Hills, Michigan, United States
      • Investigational Site Number 840028
    • Chesterfield, Michigan, United States, 48047
      • Investigational Site Number 840071
    • Dearborn, Michigan, United States, 48124
      • Investigational Site Number 840001
    • Kalamazoo, Michigan, United States, 49048
      • Investigational Site Number 840091
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • Investigational Site Number 840009
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Investigational Site Number 840024
  • Montana
    • Butte, Montana, United States, 59701
      • Investigational Site Number 840057
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Investigational Site Number 840042
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Investigational Site Number 840109
    • Las Vegas, Nevada, United States, 89148
      • Investigational Site Number 840052
  • New Hampshire
    • Nashua, New Hampshire, United States, 03063
      • Investigational Site Number 840069
  • New Jersey
    • Morganville, New Jersey, United States, 07751
      • Investigational Site Number 840123
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Investigational Site Number 840011
  • New York
    • New Hyde Park, New York, United States, 11042
      • Investigational Site Number 840030
    • Syracuse, New York, United States, 13214-2016
      • Investigational Site Number 840096
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Investigational Site Number 840039
    • Hickory, North Carolina, United States, 28601
      • Investigational Site Number 840021
    • Morehead City, North Carolina, United States, 28557
      • Investigational Site Number 840046
    • Morganton, North Carolina, United States, 28655
      • Investigational Site Number 840072
    • Salisbury, North Carolina, United States, 28144
      • Investigational Site Number 840110
    • Wilmington, North Carolina, United States, 28401
      • Investigational Site Number 840095
    • Winston-Salem, North Carolina, United States, 27103
      • Investigational Site Number 840099
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Investigational Site Number 840004
    • Maumee, Ohio, United States, 43537
      • Investigational Site Number 840016
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Investigational Site Number 840103
    • Portland, Oregon, United States, 97201-3098
      • Investigational Site Number 840113
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15473
      • Investigational Site Number 840036
    • Tipton, Pennsylvania, United States, 16684
      • Investigational Site Number 840043
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Investigational Site Number 840058
    • Charleston, South Carolina, United States, 29407
      • Investigational Site Number 840127
    • Greer, South Carolina, United States, 29651
      • Investigational Site Number 840049
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Investigational Site Number 840114
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Investigational Site Number 840112
    • Knoxville, Tennessee, United States, 37912
      • Investigational Site Number 840094
  • Texas
    • Austin, Texas, United States, 78758
      • Investigational Site Number 840051
    • Corpus Christi, Texas, United States, 78404
      • Investigational Site Number 840066
    • Dallas, Texas, United States, 75208
      • Investigational Site Number 840111
    • Dallas, Texas, United States, 75216
      • Investigational Site Number 840020
    • Dallas, Texas, United States, 75230
      • Investigational Site Number 840064
    • Dallas, Texas, United States, 75231
      • Investigational Site Number 840003
    • Edinburg, Texas, United States, 78539
      • Investigational Site Number 840088
    • Fort Worth, Texas, United States, 76132
      • Investigational Site Number 840118
    • Houston, Texas, United States, 77004
      • Investigational Site Number 840055
    • Houston, Texas, United States, 77030
      • Investigational Site Number 840087
    • Hurst, Texas, United States, 76054
      • Investigational Site Number 840079
    • N Richland Hill, Texas, United States, 76180
      • Investigational Site Number 840073
    • San Antonio, Texas, United States, 78229
      • Investigational Site Number 840019
  • Utah
    • Draper, Utah, United States, 84020
      • Investigational Site Number 840037
    • Ogden, Utah, United States, 84405
      • Investigational Site Number 840093
    • Salt Lake City, Utah, United States, 84102
      • Investigational Site Number 840061
    • Salt Lake City, Utah, United States, 84107
      • Investigational Site Number 840041
  • Virginia
    • Chesapeake, Virginia, United States, 23321
      • Investigational Site Number 840040
    • Norfolk, Virginia, United States, 23510
      • Investigational Site Number 840045
    • Norfolk, Virginia, United States, 23510
      • Investigational Site Number 840092
    • Richmond, Virginia, United States, 23219
      • Investigational Site Number 840125
    • Salem, Virginia, United States, 24153
      • Investigational Site Number 840115
    • Weber City, Virginia, United States, 24290
      • Investigational Site Number 840010
  • Washington
    • Federal Way, Washington, United States, 98003
      • Investigational Site Number 840077
    • Renton, Washington, United States, 98055
      • Investigational Site Number 840102
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209-0996
      • Investigational Site Number 840033

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Participants with type 2 diabetes mellitus diagnosed for at least 1 year before the screening visit, treated for at least 3 months prior to visit 1 with metformin alone or metformin and a second oral anti-diabetic treatment that could be a sulfonylurea, a glinide, a sodium glucose co-transporter-2 inhibitor or a di-peptidyl peptidase 4 (DPP-4) inhibitors, and who were not adequately controlled with this treatment.
• Signed written informed consent.

Exclusion criteria:

• HbA1c at screening visit:

  • less than 7.5% or more than 10% for participants previously treated with metformin alone,
  • less than 7.0% or more than 9% for participants previously treated with metformin and a second oral anti-diabetic treatment.
• Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
• Use of oral glucose-lowering agents other than those stated in the inclusion criteria or any injectable glucose-lowering agents during the 3 months before screening.
• Previous Treatment with insulin (except for short-term treatment due to intercurrent illness including gestational diabetes, at the discretion of the trial physician).
• History of discontinuation of a previous treatment with a glucagon-like peptide (GLP-1) receptor agonist (GLP-1 RA) due to safety/tolerability issue or lack of efficacy.
• Participant who previously participated in any clinical trial with lixisenatide or the insulin glargine/lixisenatide fixed ratio combination or had previously received lixisenatide.
• Any contraindication to metformin use, according to local labeling.
• Use of weight loss drugs within 3 months prior to screening visit.
• Within the last 6 months prior to screening visit: history of stroke, myocardial infarction, unstable angina, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures to be performed during the study period.
• History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy was already performed), chronic pancreatitis, pancreatitis during a previous treatment with incretin therapies, pancreatectomy, stomach/gastric surgery.
• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (e.g, multiple endocrine neoplasia syndromes).
• Uncontrolled or inadequately controlled hypertension (systolic blood pressure above 180 mmHg or diastolic blood pressure above 95 mmHg) at screening visit.
• At screening visit, Body Mass Index (BMI) less than or equal to 20 or above 40 kg/m^2.
• At screening visit amylase and/or lipase more than 3 times the upper limit of the normal (ULN) laboratory range.
• At screening visit alanine aminotransferase (ALT) or alkaline phosphatase (AST) more than 3 ULN.
• At screening visit calcitonin above or equal to 20 pg/mL (5.9 pmol/L).

Exclusion Criteria for randomization at the end of the screening period:

• HbA1c less than 7% or above 10%;
• Fasting Plasma glucose above 250 mg/dL (13.9 mmol/L);
• Metformin maximal tolerated dose less than 1500 mg/day;
• Amylase and/or lipase more than 3 ULN.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC); FRC once daily (QD) for 30 weeks. Dose individually adjusted.	Drug: Insulin glargine/lixisenatide Fixed Ratio Combination; Insulin glargine/Lixisenatide FRC was self-administered by subcutaneous (SC) injection in the morning within one hour before breakfast using one of the 2 prefilled disposable SoloStar® pen-injectors: Pen A containing 100 U/mL insulin glargine (Lantus, 100 U/mL) and 50 mcg/mL lixisenatide in a ratio of 2 U:1 mcg, used for administration of doses from 10 U to 40 U (10 U/5mcg to 40 U/20mcg). Pen B containing 100 U/mL insulin glargine (Lantus, 100 U/mL) and 33 mcg/mL lixisenatide in a ratio of 3 U:1 mcg, used to administer doses from 41 U to 60 U (41 U/13 mcg to 60 U/20 mcg). The starting dose was 10 U/5 mcg. Dose was then adjusted individually to reach and maintain fasting self-monitored plasma glucose (SMPG) of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L) while avoiding hypoglycemia.; Other Names: (HOE901/AVE0010); Drug: Metformin; Pharmaceutical form: Tablet; Route of administration: Oral administration.
Active Comparator: Insulin Glargine; Insulin glargine QD for 30 weeks. Dose individually adjusted.	Drug: Metformin; Pharmaceutical form: Tablet; Route of administration: Oral administration.; Drug: Insulin glargine (HOE901); Insulin glargine (100 U/mL) was self-administered by SC injection at approximately the same time every day. Dose was adjusted individually to reach and maintain fasting SMPG of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L) while avoiding hypoglycemia.; Other Names: Lantus
Active Comparator: Lixisenatide; Lixisenatide 10 mcg QD for 2 weeks, then 20 mcg QD (maintenance dose).	Drug: Metformin; Pharmaceutical form: Tablet; Route of administration: Oral administration.; Drug: Lixisenatide (AVE0010); Lixisenatide was self-administered by SC injection within 0 to 60 minutes before breakfast or evening meal. If the maintenance dose of 20 mcg was not tolerated, dose could be reduced to 10 mcg.; Other Names: Lyxumia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c From Baseline to 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.	Baseline, Week 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HbA1c <7.0% or ≤6.5% at Week 30	Participants without Week 30 value for HbA1c were counted as non-responders.	Week 30
Change in Plasma Glucose Excursion From Baseline to 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).	Baseline, Week 30
Change in Body Weight From Baseline to Week 30	Change in body weight was calculated by subtracting baseline value from Week 30 value.	Baseline, Week 30
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 30	Change in FPG was calculated by subtracting baseline value from Week 30 value.	Baseline, Week 30
Mean Change in 7-point Self-monitored Plasma Glucose (SMPG) Profile From Baseline to 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.	Baseline, Week 30
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	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).	Baseline up to Week 30
Average Daily Insulin Glargine Dose at 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.	Week 30
Change in 2-Hour Postprandial Plasma Glucose (PPG) From Baseline to 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.	Baseline, Week 30
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	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.	Baseline up to Week 30
Percentage of Participants Requiring Rescue Therapy During 30-Week Treatment Period	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%.	Baseline up to Week 30
Number of Documented Symptomatic Hypoglycemia Events Per Subject-Year	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).	First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days)
Percentage of Participants With Documented Symptomatic Hypoglycemia	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).	First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days)
Percentage of Participants With Severe Symptomatic Hypoglycemia	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.	First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days)

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Rosenstock J, Aronson R, Grunberger G, Hanefeld M, Piatti P, Serusclat P, Cheng X, Zhou T, Niemoeller E, Souhami E, Davies M; LixiLan-O Trial Investigators. Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide Monocomponents in Type 2 Diabetes Inadequately Controlled on Oral Agents: The LixiLan-O Randomized Trial. Diabetes Care. 2016 Nov;39(11):2026-2035. doi: 10.2337/dc16-0917. Epub 2016 Aug 15. Erratum In: Diabetes Care. 2017 Jun;40(6):809.
• Shao H, Kianmehr H, Guo J, Li P, Fonseca V, Shi L. Efficacy of iGlarLixi on 5-year risk of diabetes-related complications: A simulation study. J Diabetes Complications. 2022 Mar;36(3):108132. doi: 10.1016/j.jdiacomp.2022.108132. Epub 2022 Jan 25.
• Davies MJ, Russell-Jones D, Barber TM, Lavalle-Gonzalez FJ, Galstyan GR, Zhu D, Baxter M, Dessapt-Baradez C, McCrimmon RJ. Glycaemic benefit of iGlarLixi in insulin-naive type 2 diabetes patients with high HbA1c or those with inadequate glycaemic control on two oral antihyperglycaemic drugs in the LixiLan-O randomized trial. Diabetes Obes Metab. 2019 Aug;21(8):1967-1972. doi: 10.1111/dom.13791. Epub 2019 Jun 18.
• Dailey G, Bajaj HS, Dex T, Groleau M, Stager W, Vinik A. Post hoc efficacy and safety analysis of insulin glargine/lixisenatide fixed- ratio combination in North American patients compared with the rest of world. BMJ Open Diabetes Res Care. 2019 Mar 21;7(1):e000581. doi: 10.1136/bmjdrc-2018-000581. eCollection 2019.
• Schmider W, Belder R, Lee M, Niemoeller E, Souhami E, Frias JP. Impact of dose capping in insulin glargine/lixisenatide fixed-ratio combination trials in patients with type 2 diabetes. Curr Med Res Opin. 2019 Jun;35(6):1081-1089. doi: 10.1080/03007995.2018.1558852. Epub 2019 Jan 11.
• Rosenstock J, Handelsman Y, Vidal J, Ampudia Blasco FJ, Giorgino F, Liu M, Perfetti R, Meier JJ. Propensity-score-matched comparative analyses of simultaneously administered fixed-ratio insulin glargine 100 U and lixisenatide (iGlarLixi) vs sequential administration of insulin glargine and lixisenatide in uncontrolled type 2 diabetes. Diabetes Obes Metab. 2018 Dec;20(12):2821-2829. doi: 10.1111/dom.13462. Epub 2018 Aug 13.
• Trujillo JM, Roberts M, Dex T, Chao J, White J, LaSalle J. Low incidence of gastrointestinal adverse events over time with a fixed-ratio combination of insulin glargine and lixisenatide versus lixisenatide alone. Diabetes Obes Metab. 2018 Nov;20(11):2690-2694. doi: 10.1111/dom.13444. Epub 2018 Aug 21.
• Davies MJ, Leiter LA, Guerci B, Grunberger G, Ampudia-Blasco FJ, Yu C, Stager W, Niemoeller E, Souhami E, Rosenstock J. Impact of baseline glycated haemoglobin, diabetes duration and body mass index on clinical outcomes in the LixiLan-O trial testing a titratable fixed-ratio combination of insulin glargine/lixisenatide (iGlarLixi) vs insulin glargine and lixisenatide monocomponents. Diabetes Obes Metab. 2017 Dec;19(12):1798-1804. doi: 10.1111/dom.12980. Epub 2017 Jul 7.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: February 6, 2014
• First Submitted That Met QC Criteria: February 6, 2014
• First Posted (Estimate): February 7, 2014

Study Record Updates

• Last Update Posted (Actual): May 9, 2017
• Last Update Submitted That Met QC Criteria: March 31, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Metformin; Insulin Glargine; Lixisenatide
• Other Study ID Numbers: EFC12404; 2013-003131-30 (EudraCT Number); U1111-1148-4334 (Other Identifier: UTN)