Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus Insulin Glargine in Patients With Type 2 Diabetes
- Conditions
- Type 2 Diabetes
- Interventions
- Drug: Insulin glargine/lixisenatide (HOE901/AVE0010)Drug: Insulin glargine (HOE901)
- Registration Number
- NCT02058160
- Lead Sponsor
- Sanofi
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 736
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) Insulin glargine/lixisenatide (HOE901/AVE0010) FRC once daily (QD) for 30 weeks. Dose individually adjusted. Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) Metformin (Background Drug) FRC once daily (QD) for 30 weeks. Dose individually adjusted. Insulin glargine Insulin glargine (HOE901) Insulin glargine 100 U/mL QD for 30 weeks. Dose individually adjusted. Insulin glargine Metformin (Background Drug) Insulin glargine 100 U/mL QD for 30 weeks. Dose individually adjusted.
- Primary Outcome Measures
Name Time Method Change in Glycated Hemoglobin (HbA1c) From Baseline to Week 30 Baseline, Week 30 Change in HbA1c was calculated by subtracting baseline value from Week 30 value.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Severe Symptomatic Hypoglycemia First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine]) 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.
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 Baseline, 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.
Change in Body Weight From Baseline to Week 30 Baseline, Week 30 Change in body weight was calculated by subtracting baseline value from Week 30 value.
Mean Change in 7-point Self-monitored Plasma Glucose (SMPG) Profile From Baseline to Week 30 Baseline, Week 30 Participants recorded a 7-point plasma glucose profile measured before and 2-hours after each meal and at bedtime, two times in a week before baseline, before visit Week 12 and before visit Week 30 and the average value across the profiles performed in the week before a visit for the 7 time points was calculated. Change in average 7 point SMPG was calculated by subtracting baseline value from Week 30 value. The analysis included all scheduled measurements obtained during the study. The missing data was handled by mixed effect model with repeated measures (MMRM) approach.
Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30 Week 30 Change in Daily Insulin Glargine Dose From Baseline to Week 30 Baseline, Week 30 Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30 and No Documented Symptomatic Hypoglycemia (Plasma Glucose [PG] ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period Baseline up to Week 30 Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L).
Change in FPG From Baseline to Week 30 Baseline, Week 30 Change in FPG was calculated by subtracting baseline value from Week 30 value.
Change in 2-hour PPG From Baseline to Week 30 Baseline, Week 30 Change in PPG was calculated by subtracting baseline value from Week 30 value.
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 Baseline up to Week 30 Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L).
Percentage of Participants Requiring Rescue Therapy During 30-Week Treatment Period Baseline up to Week 30 Routine fasting SMPG and central laboratory FPG (and HbA1c after Week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after Week 12) 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%.
Number of Documented Symptomatic Hypoglycemia Events Per Subject-Year First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine]) 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).
Percentage of Participants With Documented Symptomatic Hypoglycemia First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine]) 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).
Trial Locations
- Locations (236)
Investigational Site Number 840594
🇺🇸Atlanta, Georgia, United States
Investigational Site Number 840588
🇺🇸Idaho Falls, Idaho, United States
Investigational Site Number 840580
🇺🇸Arlington Heights, Illinois, United States
Investigational Site Number 840575
🇺🇸Flint, Michigan, United States
Investigational Site Number 840600
🇺🇸Henderson, Nevada, United States
Investigational Site Number 840503
🇺🇸Maumee, Ohio, United States
Investigational Site Number 840557
🇺🇸Syracuse, New York, United States
Investigational Site Number 203511
🇨🇿Praha 4, Czech Republic
Investigational Site Number 203505
🇨🇿Prostejov, Czech Republic
Investigational Site Number 840519
🇺🇸Chicago, Illinois, United States
Investigational Site Number 840507
🇺🇸Indianapolis, Indiana, United States
Investigational Site Number 840612
🇺🇸Chicago, Illinois, United States
Investigational Site Number 840563
🇺🇸Indianapolis, Indiana, United States
Investigational Site Number 840532
🇺🇸Las Vegas, Nevada, United States
Investigational Site Number 724510
🇪🇸Barcelona, Spain
Investigational Site Number 616501
🇵🇱Warszawa, Poland
Investigational Site Number 752501
🇸🇪Ljungby, Sweden
Investigational Site Number 752504
🇸🇪Rättvik, Sweden
Investigational Site Number 840568
🇺🇸Bell Gardens, California, United States
Investigational Site Number 840522
🇺🇸Rockville, Maryland, United States
Investigational Site Number 840520
🇺🇸Baltimore, Maryland, United States
Investigational Site Number 840560
🇺🇸Baltimore, Maryland, United States
Investigational Site Number 840577
🇺🇸Tucson, Arizona, United States
Investigational Site Number 840570
🇺🇸Sun City, Arizona, United States
Investigational Site Number 840505
🇺🇸Dearborn, Michigan, United States
Investigational Site Number 840537
🇺🇸Little Rock, Arkansas, United States
Investigational Site Number 840604
🇺🇸Greenville, North Carolina, United States
Investigational Site Number 840545
🇺🇸Dallas, Texas, United States
Investigational Site Number 840613
🇺🇸Burlington, Vermont, United States
Investigational Site Number 840576
🇺🇸Albuquerque, New Mexico, United States
Investigational Site Number 840549
🇺🇸Wilmington, Delaware, United States
Investigational Site Number 840595
🇺🇸Lewiston, Maine, United States
Investigational Site Number 840558
🇺🇸Butte, Montana, United States
Investigational Site Number 840531
🇺🇸New Hyde Park, New York, United States
Investigational Site Number 840610
🇺🇸Philadelphia, Pennsylvania, United States
Investigational Site Number 840586
🇺🇸Dallas, Texas, United States
Investigational Site Number 840530
🇺🇸Dallas, Texas, United States
Investigational Site Number 152511
🇨🇱Puerto Varas, Chile
Investigational Site Number 840599
🇺🇸Las Vegas, Nevada, United States
Investigational Site Number 036505
🇦🇺Box Hill, Australia
Investigational Site Number 840592
🇺🇸Salisbury, North Carolina, United States
Investigational Site Number 840618
🇺🇸Eugene, Oregon, United States
Investigational Site Number 152503
🇨🇱Santiago, Chile
Investigational Site Number 203502
🇨🇿Cheb, Czech Republic
Investigational Site Number 840579
🇺🇸Columbus, Ohio, United States
Investigational Site Number 840601
🇺🇸Dallas, Texas, United States
Investigational Site Number 840544
🇺🇸Houston, Texas, United States
Investigational Site Number 840598
🇺🇸Austin, Texas, United States
Investigational Site Number 840513
🇺🇸Morehead City, North Carolina, United States
Investigational Site Number 840504
🇺🇸Chesapeake, Virginia, United States
Investigational Site Number 840617
🇺🇸N Richland Hill, Texas, United States
Investigational Site Number 124512
🇨🇦Brampton, Canada
Investigational Site Number 203515
🇨🇿Plzen, Czech Republic
Investigational Site Number 840593
🇺🇸Spokane, Washington, United States
Investigational Site Number 124511
🇨🇦Oakville, Canada
Investigational Site Number 840583
🇺🇸Jamaica, New York, United States
Investigational Site Number 840540
🇺🇸Hickory, North Carolina, United States
Investigational Site Number 152509
🇨🇱Talagante, Chile
Investigational Site Number 840561
🇺🇸Norfolk, Virginia, United States
Investigational Site Number 840611
🇺🇸Rapid City, South Dakota, United States
Investigational Site Number 124507
🇨🇦Kelowna, Canada
Investigational Site Number 036504
🇦🇺Parkville, Australia
Investigational Site Number 152502
🇨🇱Santiago, Chile
Investigational Site Number 152501
🇨🇱Santiago, Chile
Investigational Site Number 124504
🇨🇦Beamsville, Canada
Investigational Site Number 036501
🇦🇺Heidelberg, Australia
Investigational Site Number 124503
🇨🇦Toronto, Canada
Investigational Site Number 840608
🇺🇸Salem, Virginia, United States
Investigational Site Number 616507
🇵🇱Plock, Poland
Investigational Site Number 642510
🇷🇴Bucharest, Romania
Investigational Site Number 703511
🇸🇰Lubochna, Slovakia
Investigational Site Number 703501
🇸🇰Zilina, Slovakia
Investigational Site Number 208509
🇩🇰Horsens, Denmark
Investigational Site Number 724503
🇪🇸El Ferrol, Spain
Investigational Site Number 724505
🇪🇸Cáceres, Spain
Investigational Site Number 233502
🇪🇪Pärnu, Estonia
Investigational Site Number 440502
🇱🇹Vilnius, Lithuania
Investigational Site Number 348501
🇭🇺Budapest, Hungary
Investigational Site Number 752503
🇸🇪Malmö, Sweden
Investigational Site Number 724507
🇪🇸Segovia, Spain
Investigational Site Number 348503
🇭🇺Budapest, Hungary
Investigational Site Number 233503
🇪🇪Tallinn, Estonia
Investigational Site Number 484503
🇲🇽Guadalajara, Mexico
Investigational Site Number 724509
🇪🇸Alicante, Spain
Investigational Site Number 703509
🇸🇰Nove Zamky, Slovakia
Investigational Site Number 804510
🇺🇦Kyiv, Ukraine
Investigational Site Number 804507
🇺🇦Kyiv, Ukraine
Investigational Site Number 484506
🇲🇽Guadalajara, Mexico
Investigational Site Number 484509
🇲🇽México, Mexico
Investigational Site Number 616503
🇵🇱Warszawa, Poland
Investigational Site Number 724506
🇪🇸Alzira, Spain
Investigational Site Number 752505
🇸🇪Stockholm, Sweden
Investigational Site Number 752502
🇸🇪Vällingby, Sweden
Investigational Site Number 840564
🇺🇸Minneapolis, Minnesota, United States
Investigational Site Number 840541
🇺🇸Durham, North Carolina, United States
Investigational Site Number 840590
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 208503
🇩🇰Aarhus C, Denmark
Investigational Site Number 208502
🇩🇰Kolding, Denmark
Investigational Site Number 208501
🇩🇰København Nv, Denmark
Investigational Site Number 752506
🇸🇪Stenungssund, Sweden
Investigational Site Number 124505
🇨🇦Montreal, Canada
Investigational Site Number 124508
🇨🇦Victoria, Canada
Investigational Site Number 124509
🇨🇦St-Romuald, Canada
Investigational Site Number 724502
🇪🇸Valencia, Spain
Investigational Site Number 724504
🇪🇸Barcelona, Spain
Investigational Site Number 724508
🇪🇸La Coruña, Spain
Investigational Site Number 724501
🇪🇸Sabadell, Spain
Investigational Site Number 643508
🇷🇺Penza, Russian Federation
Investigational Site Number 840535
🇺🇸Wilmington, North Carolina, United States
Investigational Site Number 840607
🇺🇸Birmingham, Alabama, United States
Investigational Site Number 840582
🇺🇸Aurora, Colorado, United States
Investigational Site Number 840509
🇺🇸Denver, Colorado, United States
Investigational Site Number 840506
🇺🇸Omaha, Nebraska, United States
Investigational Site Number 840546
🇺🇸Milwaukee, Wisconsin, United States
Investigational Site Number 840516
🇺🇸Louisville, Kentucky, United States
Investigational Site Number 840572
🇺🇸West Hills, California, United States
Investigational Site Number 840584
🇺🇸Tipton, Pennsylvania, United States
Investigational Site Number 840551
🇺🇸Smithfield, Pennsylvania, United States
Investigational Site Number 840515
🇺🇸Winston-Salem, North Carolina, United States
Investigational Site Number 840514
🇺🇸Hurst, Texas, United States
Investigational Site Number 124510
🇨🇦Toronto, Canada
Investigational Site Number 840502
🇺🇸Corpus Christi, Texas, United States
Investigational Site Number 840571
🇺🇸Federal Way, Washington, United States
Investigational Site Number 840526
🇺🇸Ogden, Utah, United States
Investigational Site Number 124502
🇨🇦Guelph, Canada
Investigational Site Number 840562
🇺🇸Tempe, Arizona, United States
Investigational Site Number 840517
🇺🇸Little Rock, Arkansas, United States
Investigational Site Number 840529
🇺🇸Chula Vista, California, United States
Investigational Site Number 840623
🇺🇸Corona, California, United States
Investigational Site Number 840550
🇺🇸Chino, California, United States
Investigational Site Number 840581
🇺🇸Los Angeles, California, United States
Investigational Site Number 840578
🇺🇸Lancaster, California, United States
Investigational Site Number 840626
🇺🇸Los Angeles, California, United States
Investigational Site Number 840566
🇺🇸Fresno, California, United States
Investigational Site Number 840621
🇺🇸Mission Viejo, California, United States
Investigational Site Number 840511
🇺🇸Northridge, California, United States
Investigational Site Number 840552
🇺🇸Greenbrae, California, United States
Investigational Site Number 840573
🇺🇸Palm Springs, California, United States
Investigational Site Number 840567
🇺🇸Santa Ana, California, United States
Investigational Site Number 840559
🇺🇸Port Hueneme, California, United States
Investigational Site Number 840536
🇺🇸San Ramon, California, United States
Investigational Site Number 840569
🇺🇸Tarzana, California, United States
Investigational Site Number 840510
🇺🇸Miami, Florida, United States
Investigational Site Number 840521
🇺🇸New Port Richey, Florida, United States
Investigational Site Number 840538
🇺🇸Ocoee, Florida, United States
Investigational Site Number 840602
🇺🇸Ocala, Florida, United States
Investigational Site Number 840534
🇺🇸Palm Harbor, Florida, United States
Investigational Site Number 840614
🇺🇸Columbus, Georgia, United States
Investigational Site Number 840501
🇺🇸Lawrenceville, Georgia, United States
Investigational Site Number 840525
🇺🇸Roswell, Georgia, United States
Investigational Site Number 840543
🇺🇸Avon, Indiana, United States
Investigational Site Number 840556
🇺🇸Springfield, Illinois, United States
Investigational Site Number 840565
🇺🇸Evansville, Indiana, United States
Investigational Site Number 840615
🇺🇸Evansville, Indiana, United States
Investigational Site Number 840585
🇺🇸Evansville, Indiana, United States
Investigational Site Number 840539
🇺🇸Nashua, New Hampshire, United States
Investigational Site Number 840524
🇺🇸Dayton, Ohio, United States
Investigational Site Number 840622
🇺🇸Charleston, South Carolina, United States
Investigational Site Number 840547
🇺🇸Dallas, Texas, United States
Investigational Site Number 840553
🇺🇸Austin, Texas, United States
Investigational Site Number 840597
🇺🇸Orem, Utah, United States
Investigational Site Number 840591
🇺🇸Murray, Utah, United States
Investigational Site Number 840512
🇺🇸Draper, Utah, United States
Investigational Site Number 840609
🇺🇸Tacoma, Washington, United States
Investigational Site Number 840606
🇺🇸Richmond, Virginia, United States
Investigational Site Number 124501
🇨🇦Vancouver, Canada
Investigational Site Number 203504
🇨🇿Hranice, Czech Republic
Investigational Site Number 152504
🇨🇱Vina Del Mar, Chile
Investigational Site Number 203503
🇨🇿Olomouc, Czech Republic
Investigational Site Number 233501
🇪🇪Tartu, Estonia
Investigational Site Number 440503
🇱🇹Kaunas, Lithuania
Investigational Site Number 208505
🇩🇰København S, Denmark
Investigational Site Number 208504
🇩🇰Viborg, Denmark
Investigational Site Number 440505
🇱🇹Kedainiai, Lithuania
Investigational Site Number 440504
🇱🇹Klaipeda, Lithuania
Investigational Site Number 484501
🇲🇽Cuernavaca, Mexico
Investigational Site Number 484508
🇲🇽Celaya, Mexico
Investigational Site Number 484504
🇲🇽Guadalajara, Mexico
Investigational Site Number 616502
🇵🇱Bialystok, Poland
Investigational Site Number 484507
🇲🇽Pachuca, Mexico
Investigational Site Number 528505
🇳🇱Almere, Netherlands
Investigational Site Number 616505
🇵🇱Krakow, Poland
Investigational Site Number 616506
🇵🇱Krakow, Poland
Investigational Site Number 642507
🇷🇴Brasov, Romania
Investigational Site Number 642506
🇷🇴Hunedoara, Romania
Investigational Site Number 642502
🇷🇴Oradea, Romania
Investigational Site Number 642501
🇷🇴Targu Mures, Romania
Investigational Site Number 642505
🇷🇴Iasi, Romania
Investigational Site Number 642511
🇷🇴Sibiu, Romania
Investigational Site Number 642504
🇷🇴Timisoara, Romania
Investigational Site Number 643511
🇷🇺Arkhangelsk, Russian Federation
Investigational Site Number 643512
🇷🇺Moscow, Russian Federation
Investigational Site Number 643501
🇷🇺Saint-Petersburg, Russian Federation
Investigational Site Number 643507
🇷🇺Saratov, Russian Federation
Investigational Site Number 643513
🇷🇺Samara, Russian Federation
Investigational Site Number 643503
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 643506
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 643514
🇷🇺Saratov, Russian Federation
Investigational Site Number 643504
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 643505
🇷🇺St. Petersburg, Russian Federation
Investigational Site Number 643502
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 643509
🇷🇺Voronezh, Russian Federation
Investigational Site Number 703505
🇸🇰Bratislava, Slovakia
Investigational Site Number 703507
🇸🇰Bytca, Slovakia
Investigational Site Number 703512
🇸🇰Kosice, Slovakia
Investigational Site Number 703502
🇸🇰Kosice, Slovakia
Investigational Site Number 703510
🇸🇰Kosice, Slovakia
Investigational Site Number 152507
🇨🇱Santiago, Chile
Investigational Site Number 152514
🇨🇱Santiago, Chile
Investigational Site Number 203506
🇨🇿Liberec, Czech Republic
Investigational Site Number 348506
🇭🇺Kaposvár, Hungary
Investigational Site Number 642508
🇷🇴Bucuresti, Romania
Investigational Site Number 703513
🇸🇰Trnava, Slovakia
Investigational Site Number 484505
🇲🇽Puebla, Mexico
Investigational Site Number 152513
🇨🇱Temuco, Chile
Investigational Site Number 203507
🇨🇿Krnov, Czech Republic
Investigational Site Number 203508
🇨🇿Praha 5, Czech Republic
Investigational Site Number 203509
🇨🇿Praha 8, Czech Republic
Investigational Site Number 348502
🇭🇺Debrecen, Hungary
Investigational Site Number 616504
🇵🇱Szczecin, Poland
Investigational Site Number 703504
🇸🇰Nove Mesto Nad Vahom, Slovakia
Investigational Site Number 348505
🇭🇺Budapest, Hungary
Investigational Site Number 203514
🇨🇿Plzen, Czech Republic
Investigational Site Number 348504
🇭🇺Pápa, Hungary
Investigational Site Number 440501
🇱🇹Kaunas, Lithuania
Investigational Site Number 642509
🇷🇴Bucuresti, Romania
Investigational Site Number 642503
🇷🇴Timisoara, Romania
Investigational Site Number 703508
🇸🇰Moldava Nad Bodvou, Slovakia
Investigational Site Number 804501
🇺🇦Chernivtsi, Ukraine
Investigational Site Number 804513
🇺🇦Lviv, Ukraine
Investigational Site Number 804511
🇺🇦Kyiv, Ukraine
Investigational Site Number 804502
🇺🇦Vinnytsya, Ukraine
Investigational Site Number 804508
🇺🇦Vinnytsya, Ukraine
Investigational Site Number 840625
🇺🇸Norfolk, Virginia, United States
Investigational Site Number 840605
🇺🇸Amarillo, Texas, United States
Investigational Site Number 840554
🇺🇸Edinburg, Texas, United States