Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus Insulin Glargine in Patients With Type 2 Diabetes (LixiLan-L)

A Randomized, 30-week, Active-controlled, Open Label, 2- Treatment Arm, Parallel-group, Multicenter Study Comparing the Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination to Insulin Glargine With or Without Metformin in Patients With Type 2 Diabetes Mellitus (T2DM)

Primary Objective:

To demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination (FRC) to insulin glargine in glycated hemoglobin (HbA1c) change from baseline to Week 30.

Secondary Objective:

To compare the overall efficacy and safety of insulin glargine/lixisenatide FRC to insulin glargine (with or without metformin) 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 (HOE901/AVE0010); Drug: Metformin (Background Drug); Drug: Insulin glargine (HOE901)

Detailed Description

Maximum duration of approximately 39 weeks: an up to 8-week screening period, a 30-week randomized treatment period and 3 days post-treatment safety follow up period.

• Study Type: Interventional
• Enrollment (Actual): 736
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
    • Investigational Site Number 036505
  • Heidelberg, Australia, 3081
    • Investigational Site Number 036501
  • Parkville, Australia, 3050
    • Investigational Site Number 036504
• Canada
  • Beamsville, Canada, L0R 1B0
    • Investigational Site Number 124504
  • Brampton, Canada, L6R 3J5
    • Investigational Site Number 124512
  • Guelph, Canada, N1H 1B1
    • Investigational Site Number 124502
  • Kelowna, Canada, V1Y 1Z9
    • Investigational Site Number 124507
  • Montreal, Canada, H1W 2R7
    • Investigational Site Number 124505
  • Oakville, Canada, L6H 3P1
    • Investigational Site Number 124511
  • St-Romuald, Canada, G6W 5M6
    • Investigational Site Number 124509
  • Toronto, Canada, M9V 4B4
    • Investigational Site Number 124503
  • Toronto, Canada, M9W 4L9
    • Investigational Site Number 124510
  • Vancouver, Canada, V5Y 3W2
    • Investigational Site Number 124501
  • Victoria, Canada, V8V 4A1
    • Investigational Site Number 124508
• Chile
  • Puerto Varas, Chile, 5480000
    • Investigational Site Number 152511
  • Santiago, Chile, 7500347
    • Investigational Site Number 152502
  • Santiago, Chile, 7500710
    • Investigational Site Number 152501
  • Santiago, Chile, 7500739
    • Investigational Site Number 152514
  • Santiago, Chile, 8053095
    • Investigational Site Number 152503
  • Santiago, Chile
    • Investigational Site Number 152507
  • Talagante, Chile
    • Investigational Site Number 152509
  • Temuco, Chile, 4780000
    • Investigational Site Number 152513
  • Vina Del Mar, Chile
    • Investigational Site Number 152504
• Czech Republic
  • Cheb, Czech Republic, 35002
    • Investigational Site Number 203502
  • Hranice, Czech Republic, 75301
    • Investigational Site Number 203504
  • Krnov, Czech Republic, 79401
    • Investigational Site Number 203507
  • Liberec, Czech Republic, 460 01
    • Investigational Site Number 203506
  • Olomouc, Czech Republic, 77900
    • Investigational Site Number 203503
  • Plzen, Czech Republic, 301 66
    • Investigational Site Number 203514
  • Plzen, Czech Republic, 301 66
    • Investigational Site Number 203515
  • Praha 4, Czech Republic, 14900
    • Investigational Site Number 203511
  • Praha 5, Czech Republic, 15030
    • Investigational Site Number 203508
  • Praha 8, Czech Republic, 18100
    • Investigational Site Number 203509
  • Prostejov, Czech Republic, 79601
    • Investigational Site Number 203505
• Denmark
  • Aarhus C, Denmark, 8000
    • Investigational Site Number 208503
  • Horsens, Denmark, 8700
    • Investigational Site Number 208509
  • Kolding, Denmark, 6000
    • Investigational Site Number 208502
  • København Nv, Denmark, 2400
    • Investigational Site Number 208501
  • København S, Denmark, 2300
    • Investigational Site Number 208505
  • Viborg, Denmark, 8800
    • Investigational Site Number 208504
• Estonia
  • Pärnu, Estonia, 80018
    • Investigational Site Number 233502
  • Tallinn, Estonia, 10138
    • Investigational Site Number 233503
  • Tartu, Estonia, 50406
    • Investigational Site Number 233501
• Hungary
  • Budapest, Hungary, 1134
    • Investigational Site Number 348503
  • Budapest, Hungary, 1138
    • Investigational Site Number 348501
  • Budapest, Hungary, 1212
    • Investigational Site Number 348505
  • Debrecen, Hungary, 4031
    • Investigational Site Number 348502
  • Kaposvár, Hungary, 7400
    • Investigational Site Number 348506
  • Pápa, Hungary, 8500
    • Investigational Site Number 348504
• Lithuania
  • Kaunas, Lithuania, 48259
    • Investigational Site Number 440501
  • Kaunas, Lithuania, 49449
    • Investigational Site Number 440503
  • Kedainiai, Lithuania, LT-57164
    • Investigational Site Number 440505
  • Klaipeda, Lithuania, LT-92253
    • Investigational Site Number 440504
  • Vilnius, Lithuania, LT-10323
    • Investigational Site Number 440502
• Mexico
  • Celaya, Mexico, 38000
    • Investigational Site Number 484508
  • Cuernavaca, Mexico, 62250
    • Investigational Site Number 484501
  • Guadalajara, Mexico, 44130
    • Investigational Site Number 484503
  • Guadalajara, Mexico, 44210
    • Investigational Site Number 484504
  • Guadalajara, Mexico, 44600
    • Investigational Site Number 484506
  • México, Mexico, 06700
    • Investigational Site Number 484509
  • Pachuca, Mexico, 42084
    • Investigational Site Number 484507
  • Puebla, Mexico, 72190
    • Investigational Site Number 484505
• Netherlands
  • Almere, Netherlands, 1311 RL
    • Investigational Site Number 528505
• Poland
  • Bialystok, Poland, 15-435
    • Investigational Site Number 616502
  • Krakow, Poland, 31-261
    • Investigational Site Number 616505
  • Krakow, Poland, 31-548
    • Investigational Site Number 616506
  • Plock, Poland, 09-400
    • Investigational Site Number 616507
  • Szczecin, Poland, 70-506
    • Investigational Site Number 616504
  • Warszawa, Poland, 01-518
    • Investigational Site Number 616503
  • Warszawa, Poland, 02-507
    • Investigational Site Number 616501
• Romania
  • Brasov, Romania, 500365
    • Investigational Site Number 642507
  • Bucharest, Romania, 010825
    • Investigational Site Number 642510
  • Bucuresti, Romania, 020042
    • Investigational Site Number 642508
  • Bucuresti, Romania, 020475
    • Investigational Site Number 642509
  • Hunedoara, Romania, 331057
    • Investigational Site Number 642506
  • Iasi, Romania, 700547
    • Investigational Site Number 642505
  • Oradea, Romania, 410169
    • Investigational Site Number 642502
  • Sibiu, Romania, 550371
    • Investigational Site Number 642511
  • Targu Mures, Romania, 540142
    • Investigational Site Number 642501
  • Timisoara, Romania, 300125
    • Investigational Site Number 642504
  • Timisoara, Romania, 300456
    • Investigational Site Number 642503
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Investigational Site Number 643511
  • Moscow, Russian Federation, 119435
    • Investigational Site Number 643512
  • Penza, Russian Federation, 440026
    • Investigational Site Number 643508
  • Saint-Petersburg, Russian Federation, 190013
    • Investigational Site Number 643501
  • Samara, Russian Federation, 443041
    • Investigational Site Number 643513
  • Saratov, Russian Federation, 410030
    • Investigational Site Number 643507
  • Saratov, Russian Federation, 410053
    • Investigational Site Number 643514
  • St-Petersburg, Russian Federation, 194291
    • Investigational Site Number 643506
  • St-Petersburg, Russian Federation, 194354
    • Investigational Site Number 643503
  • St-Petersburg, Russian Federation, 194354
    • Investigational Site Number 643504
  • St-Petersburg, Russian Federation, 195257
    • Investigational Site Number 643502
  • St. Petersburg, Russian Federation, 194358
    • Investigational Site Number 643505
  • Voronezh, Russian Federation, 394018
    • Investigational Site Number 643509
• Slovakia
  • Bratislava, Slovakia, 85101
    • Investigational Site Number 703505
  • Bytca, Slovakia, 01401
    • Investigational Site Number 703507
  • Kosice, Slovakia, 04001
    • Investigational Site Number 703502
  • Kosice, Slovakia, 04001
    • Investigational Site Number 703512
  • Kosice, Slovakia, 04013
    • Investigational Site Number 703510
  • Lubochna, Slovakia, 3491
    • Investigational Site Number 703511
  • Moldava Nad Bodvou, Slovakia, 04525
    • Investigational Site Number 703508
  • Nove Mesto Nad Vahom, Slovakia, 91501
    • Investigational Site Number 703504
  • Nove Zamky, Slovakia, 94001
    • Investigational Site Number 703509
  • Trnava, Slovakia, 91701
    • Investigational Site Number 703513
  • Zilina, Slovakia, 01001
    • Investigational Site Number 703501
• Spain
  • Alicante, Spain, 03010
    • Investigational Site Number 724509
  • Alzira, Spain, 46600
    • Investigational Site Number 724506
  • Barcelona, Spain, 08035
    • Investigational Site Number 724504
  • Barcelona, Spain, 08036
    • Investigational Site Number 724510
  • Cáceres, Spain, 10003
    • Investigational Site Number 724505
  • El Ferrol, Spain, 15405
    • Investigational Site Number 724503
  • La Coruña, Spain, 15006
    • Investigational Site Number 724508
  • Sabadell, Spain, 08208
    • Investigational Site Number 724501
  • Segovia, Spain, 40002
    • Investigational Site Number 724507
  • Valencia, Spain, 46014
    • Investigational Site Number 724502
• Sweden
  • Ljungby, Sweden, 341 82
    • Investigational Site Number 752501
  • Malmö, Sweden, 211 52
    • Investigational Site Number 752503
  • Rättvik, Sweden, 79530
    • Investigational Site Number 752504
  • Stenungssund, Sweden, 44431
    • Investigational Site Number 752506
  • Stockholm, Sweden, 11526
    • Investigational Site Number 752505
  • Vällingby, Sweden, 16268
    • Investigational Site Number 752502
• Ukraine
  • Chernivtsi, Ukraine, 58022
    • Investigational Site Number 804501
  • Kyiv, Ukraine, 03049
    • Investigational Site Number 804510
  • Kyiv, Ukraine, 04050
    • Investigational Site Number 804507
  • Kyiv, Ukraine
    • Investigational Site Number 804511
  • Lviv, Ukraine, 79010
    • Investigational Site Number 804513
  • Vinnytsya, Ukraine, 21001
    • Investigational Site Number 804502
  • Vinnytsya, Ukraine, 21010
    • Investigational Site Number 804508
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Investigational Site Number 840607
  • Arizona
    • Sun City, Arizona, United States, 85351
      • Investigational Site Number 840570
    • Tempe, Arizona, United States
      • Investigational Site Number 840562
    • Tucson, Arizona, United States, 85723
      • Investigational Site Number 840577
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Investigational Site Number 840517
    • Little Rock, Arkansas, United States, 72205
      • Investigational Site Number 840537
  • California
    • Bell Gardens, California, United States, 90201
      • Investigational Site Number 840568
    • Chino, California, United States, 91710
      • Investigational Site Number 840550
    • Chula Vista, California, United States, 91911
      • Investigational Site Number 840529
    • Corona, California, United States, 92879
      • Investigational Site Number 840623
    • Fresno, California, United States, 93720
      • Investigational Site Number 840566
    • Greenbrae, California, United States, 94904
      • Investigational Site Number 840552
    • Lancaster, California, United States, 93534
      • Investigational Site Number 840578
    • Los Angeles, California, United States, 90017
      • Investigational Site Number 840626
    • Los Angeles, California, United States, 90057
      • Investigational Site Number 840581
    • Mission Viejo, California, United States, 92691
      • Investigational Site Number 840621
    • Northridge, California, United States, 91325
      • Investigational Site Number 840511
    • Palm Springs, California, United States, 92262
      • Investigational Site Number 840573
    • Port Hueneme, California, United States, 93041
      • Investigational Site Number 840559
    • San Ramon, California, United States, 94583
      • Investigational Site Number 840536
    • Santa Ana, California, United States, 92704
      • Investigational Site Number 840567
    • Tarzana, California, United States, 91356
      • Investigational Site Number 840569
    • West Hills, California, United States, 91345
      • Investigational Site Number 840572
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Investigational Site Number 840582
    • Denver, Colorado, United States, 80246
      • Investigational Site Number 840509
  • Delaware
    • Wilmington, Delaware, United States, 19713
      • Investigational Site Number 840549
  • Florida
    • Miami, Florida, United States, 33156-7563
      • Investigational Site Number 840510
    • New Port Richey, Florida, United States, 34652
      • Investigational Site Number 840521
    • Ocala, Florida, United States, 34471
      • Investigational Site Number 840602
    • Ocoee, Florida, United States, 34761
      • Investigational Site Number 840538
    • Palm Harbor, Florida, United States, 34684
      • Investigational Site Number 840534
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Investigational Site Number 840594
    • Columbus, Georgia, United States, 31904
      • Investigational Site Number 840614
    • Lawrenceville, Georgia, United States, 30046
      • Investigational Site Number 840501
    • Roswell, Georgia, United States, 30076
      • Investigational Site Number 840525
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Investigational Site Number 840588
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Investigational Site Number 840580
    • Chicago, Illinois, United States, 60607
      • Investigational Site Number 840519
    • Chicago, Illinois, United States, 60616
      • Investigational Site Number 840612
    • Springfield, Illinois, United States, 62704
      • Investigational Site Number 840556
  • Indiana
    • Avon, Indiana, United States, 46123
      • Investigational Site Number 840543
    • Evansville, Indiana, United States, 47713
      • Investigational Site Number 840565
    • Evansville, Indiana, United States, 47714
      • Investigational Site Number 840585
    • Evansville, Indiana, United States, 47714
      • Investigational Site Number 840615
    • Indianapolis, Indiana, United States, 46202
      • Investigational Site Number 840563
    • Indianapolis, Indiana, United States, 46260
      • Investigational Site Number 840507
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • Investigational Site Number 840516
  • Maine
    • Lewiston, Maine, United States, 04240
      • Investigational Site Number 840595
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Investigational Site Number 840520
    • Baltimore, Maryland, United States, 21237
      • Investigational Site Number 840560
    • Rockville, Maryland, United States, 20852
      • Investigational Site Number 840522
  • Michigan
    • Dearborn, Michigan, United States, 48124
      • Investigational Site Number 840505
    • Flint, Michigan, United States, 48504
      • Investigational Site Number 840575
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • Investigational Site Number 840564
  • Montana
    • Butte, Montana, United States, 59701
      • Investigational Site Number 840558
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Investigational Site Number 840506
  • Nevada
    • Henderson, Nevada, United States, 89074
      • Investigational Site Number 840600
    • Las Vegas, Nevada, United States, 89119
      • Investigational Site Number 840532
    • Las Vegas, Nevada, United States, 89148
      • Investigational Site Number 840599
  • New Hampshire
    • Nashua, New Hampshire, United States, 03063
      • Investigational Site Number 840539
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Investigational Site Number 840576
  • New York
    • Jamaica, New York, United States, 11432
      • Investigational Site Number 840583
    • New Hyde Park, New York, United States, 11042
      • Investigational Site Number 840531
    • Syracuse, New York, United States, 13214-2016
      • Investigational Site Number 840557
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Investigational Site Number 840541
    • Greenville, North Carolina, United States, 27858
      • Investigational Site Number 840604
    • Hickory, North Carolina, United States, 28601
      • Investigational Site Number 840540
    • Morehead City, North Carolina, United States, 28557
      • Investigational Site Number 840513
    • Salisbury, North Carolina, United States, 28144
      • Investigational Site Number 840592
    • Wilmington, North Carolina, United States, 28401
      • Investigational Site Number 840535
    • Winston-Salem, North Carolina, United States, 27103
      • Investigational Site Number 840515
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Investigational Site Number 840579
    • Dayton, Ohio, United States, 45439
      • Investigational Site Number 840524
    • Maumee, Ohio, United States, 43537
      • Investigational Site Number 840503
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Investigational Site Number 840618
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Investigational Site Number 840610
    • Smithfield, Pennsylvania, United States, 15478
      • Investigational Site Number 840551
    • Tipton, Pennsylvania, United States, 16684
      • Investigational Site Number 840584
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Investigational Site Number 840622
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Investigational Site Number 840611
  • Texas
    • Amarillo, Texas, United States, 79106
      • Investigational Site Number 840605
    • Austin, Texas, United States, 78731
      • Investigational Site Number 840553
    • Austin, Texas, United States, 78731
      • Investigational Site Number 840598
    • Corpus Christi, Texas, United States, 78404
      • Investigational Site Number 840502
    • Dallas, Texas, United States, 75208
      • Investigational Site Number 840601
    • Dallas, Texas, United States, 75216
      • Investigational Site Number 840586
    • Dallas, Texas, United States, 75230
      • Investigational Site Number 840547
    • Dallas, Texas, United States, 75231
      • Investigational Site Number 840530
    • Dallas, Texas, United States, 75246
      • Investigational Site Number 840545
    • Edinburg, Texas, United States, 78539
      • Investigational Site Number 840554
    • Houston, Texas, United States, 77030
      • Investigational Site Number 840544
    • Hurst, Texas, United States, 76054
      • Investigational Site Number 840514
    • N Richland Hill, Texas, United States, 76180
      • Investigational Site Number 840617
  • Utah
    • Draper, Utah, United States, 84020
      • Investigational Site Number 840512
    • Murray, Utah, United States, 84123
      • Investigational Site Number 840591
    • Ogden, Utah, United States, 84405
      • Investigational Site Number 840526
    • Orem, Utah, United States, 84058
      • Investigational Site Number 840597
    • Salt Lake City, Utah, United States, 84102
      • Investigational Site Number 840590
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Investigational Site Number 840613
  • Virginia
    • Chesapeake, Virginia, United States, 23321
      • Investigational Site Number 840504
    • Norfolk, Virginia, United States, 23510
      • Investigational Site Number 840561
    • Norfolk, Virginia, United States, 23510
      • Investigational Site Number 840625
    • Richmond, Virginia, United States, 23227
      • Investigational Site Number 840606
    • Salem, Virginia, United States, 24153
      • Investigational Site Number 840608
  • Washington
    • Federal Way, Washington, United States, 98003
      • Investigational Site Number 840571
    • Spokane, Washington, United States, 99220
      • Investigational Site Number 840593
    • Tacoma, Washington, United States, 98415-0299
      • Investigational Site Number 840609
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209-0996
      • Investigational Site Number 840546

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Type 2 diabetes mellitus diagnosed at least 1 year before the screening visit.
• Treatment with basal insulin for at least 6 months before the screening visit.
• Stable basal insulin regimen (i.e. type of insulin and time/frequency of the injection) for at least 3 months before the screening visit.
• Stable (plus/minus 20 percent) total daily basal insulin dose between 15 and 40 Units/day for at least 2 months prior to the screening visit.

• For participants receiving basal insulin and 1 or 2 oral anti-diabetic drugs (OADs): the OAD dose(s) must be stable during the 3 months before the screening visit. The OADs could be 1 to 2 out of:

  • metformin (more than or equal to 1500 mg/day or maximal tolerated dose),
  • a sulfonylurea,
  • a glinide,
  • a dipeptidyl-peptidase-4 inhibitor,
  • a sodium glucose co-transporter 2 inhibitor,
• Fasting Plasma Glucose (FPG) less than or equal to 180 mg/dL(10.0 mmol/L) at screening visit for participants receiving basal insulin in combination with 2 OADs or with 1 OAD other than metformin; FPG less than or equal to 200 mg/dL (11.1 mmol/L) at screening visit for participants on basal insulin only or basal insulin plus metformin at screening visit.
• Signed written informed consent.

Exclusion criteria:

• Age under legal age of adulthood at screening visit.
• HbA1c at screening visit less than 7.5% or above 10%.
• Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
• Use of other oral or injectable glucose-lowering agents than stated in the inclusion criteria in a period of 3 months prior to screening.
• Previous use of insulin other than basal insulin eg, prandial or pre-mixed insulin, in the year prior to screening. Note: Short term treatment (≤10 days) due to intercurrent illness is allowed.
• History discontinuation of a previous treatment with Glucagon Like Peptide -1 Receptor Agonists for safety/tolerability or lack of efficacy.
• Participant who had previously participated in any clinical trial with lixisenatide or the insulin glargine/lixisenatide FRC or had previously received lixisenatide.
• 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 (eg, 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).
• Any contraindication to metformin use, according to local labeling, if the participant was taking metformin.
• Participant who had a renal function impairment with creatinine clearance less than 30 mL/min (using the Cockcroft and Gault formula) or end-stage renal disease for participants, not treated with metformin.

Exclusion criteria for randomization:

• HbA1c less than 7% or above 10% .
• Mean fasting SMPG calculated from the self-measurements for 7 days the week before randomization visit was above 140 mg/dL (7.8 mmol/L).
• Average insulin glargine daily dose less than 20 Units or above 50 Units (in the week before randomization visit).
• 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

2

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 (HOE901/AVE0010); Insulin glargine/lixisenatide FRC was self-administered by subcutaneous (SC) injection within 1 hour before breakfast using one of 2 SoloStar® pen-injectors: Pen A (ratio of 2 Units (U) of insulin glargine U 100:1 mcg of lixisenatide) or Pen B (ratio of 3 U of insulin glargine U 100:1 mcg of lixisenatide). After run-in, the FRC was initiated at a dose of either 20 U/10 mcg with Pen A or 30 U/10 mcg with Pen B, depending on participant's dose of Insulin glargine on the day prior to randomization. Dose was adjusted weekly 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). Pen A was used for administration of doses up to 40 U/20 mcg and Pen B for administration of doses from 30 U/10 mcg up to 60 U/20 mcg.; Drug: Metformin (Background Drug); Pharmaceutical form: Tablet; Route of administration: Oral administration
Active Comparator: Insulin glargine; Insulin glargine 100 U/mL QD for 30 weeks. Dose individually adjusted.	Drug: Metformin (Background Drug); Pharmaceutical form: Tablet; Route of administration: Oral administration; Drug: Insulin glargine (HOE901); Insulin glargine was self-administered QD by SC injection at approximately the same time every day. After screening, eligible participants entered 6 week run-in phase during which they were switched (if necessary) to insulin glargine and dose was stabilized. The first dose after randomization was same as the one administered on the day prior to randomization and then dose was adjusted weekly to reach and maintain fasting SMPG of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L).; Other Names: Lantus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycated Hemoglobin (HbA1c) From Baseline to Week 30	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
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
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
Percentage of Participants With HbA1c <7.0% or ≤6.5% at Week 30		Week 30
Change in 2-hour Plasma Blood Glucose Excursion From Baseline to Week 30	Plasma glucose excursion = 2-hour postprandial glucose (PPG) minus plasma glucose value obtained 30 minutes prior to the start of the meal and before investigational medicinal product (IMP) administration, if IMP was injected before breakfast. Change in plasma glucose excursions 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
Change in Daily Insulin Glargine Dose From Baseline to Week 30		Baseline, Week 30
Change in FPG From Baseline to Week 30	Change in FPG was calculated by subtracting baseline value from Week 30 value.	Baseline, Week 30
Change in 2-hour PPG From Baseline to Week 30	Change in PPG was calculated by subtracting baseline value from Week 30 value.	Baseline, Week 30
Percentage of Participants Reaching HbA1c <7.0% 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).	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) were 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 typical 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 [FRC], 210 days [Insulin glargine])
Percentage of Participants With Documented Symptomatic Hypoglycemia	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).	First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])
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 had 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 for injury to themselves or others.	First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• 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.
• Aroda VR, Rosenstock J, Wysham C, Unger J, Bellido D, Gonzalez-Galvez G, Takami A, Guo H, Niemoeller E, Souhami E, Bergenstal RM; LixiLan-L Trial Investigators. Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide in Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin: The LixiLan-L Randomized Trial. Diabetes Care. 2016 Nov;39(11):1972-1980. doi: 10.2337/dc16-1495. Epub 2016 Sep 20. Erratum In: Diabetes Care. 2017 Jun;40(6):809.
• Tabak AG, Anderson J, Aschner P, Liu M, Saremi A, Stella P, Tinahones FJ, Wysham C, Meier JJ. Efficacy and Safety of iGlarLixi, Fixed-Ratio Combination of Insulin Glargine and Lixisenatide, Compared with Basal-Bolus Regimen in Patients with Type 2 Diabetes: Propensity Score Matched Analysis. Diabetes Ther. 2020 Jan;11(1):305-318. doi: 10.1007/s13300-019-00735-7. Epub 2019 Dec 17.
• Blonde L, Bailey TS, Chao J, Dex TA, Frias JP, Meneghini LF, Roberts M, Aroda VR. Clinical Characteristics and Glycemic Outcomes of Patients with Type 2 Diabetes Requiring Maximum Dose Insulin Glargine/Lixisenatide Fixed-Ratio Combination or Insulin Glargine in the LixiLan-L Trial. Adv Ther. 2019 Sep;36(9):2310-2326. doi: 10.1007/s12325-019-01033-1. Epub 2019 Jul 29.
• Zisman A, Dex T, Roberts M, Saremi A, Chao J, Aroda VR. Bedtime-to-Morning Glucose Difference and iGlarLixi in Type 2 Diabetes: Post Hoc Analysis of LixiLan-L. Diabetes Ther. 2018 Oct;9(5):2155-2162. doi: 10.1007/s13300-018-0507-0. Epub 2018 Sep 14. Erratum In: Diabetes Ther. 2018 Dec 4;:
• Niemoeller E, Souhami E, Wu Y, Jensen KH. iGlarLixi Reduces Glycated Hemoglobin to a Greater Extent Than Basal Insulin Regardless of Levels at Screening: Post Hoc Analysis of LixiLan-L. Diabetes Ther. 2018 Feb;9(1):373-382. doi: 10.1007/s13300-017-0336-6. Epub 2017 Nov 16.
• Wysham C, Bonadonna RC, Aroda VR, Puig Domingo M, Kapitza C, Stager W, Yu C, Niemoeller E, Souhami E, Bergenstal RM; LixiLan-L trial investigators. Consistent findings in glycaemic control, body weight and hypoglycaemia with iGlarLixi (insulin glargine/lixisenatide titratable fixed-ratio combination) vs insulin glargine across baseline HbA1c, BMI and diabetes duration categories in the LixiLan-L trial. Diabetes Obes Metab. 2017 Oct;19(10):1408-1415. doi: 10.1111/dom.12961. Epub 2017 Jun 8.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 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: EFC12405; 2013-003132-79 (EudraCT Number); U1111-1148-4351 (Other Identifier: UTN)