Efficacy and Safety of Lixisenatide Versus Insulin Glulisine on Top of Insulin Glargine With or Without Metformin in Type 2 Diabetic Patients
- Conditions
- Type 2 Diabetes
- Interventions
- Drug: Insulin glulisine QDDrug: Insulin glulisine TIDDrug: Insulin Glargine (Mandatory background drug)
- Registration Number
- NCT01768559
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
- To compare lixisenatide versus insulin glulisine in terms of glycosylated hemoglobin (HbA1c) reduction and body weight change at Week 26 in type 2 diabetic participants not adequately controlled on insulin glargine ± metformin.
Secondary Objectives:
- To compare the treatments/regimens on:
* The percentage of participants reaching the target of HbA1c \<7% or ≤6.5%,
* Body weight,
* Self-Monitored Glucose profiles,
* Fasting Plasma Glucose (FPG),
* Post-prandial plasma glucose (PPG) /glucose excursions during a standardized meal test (subset of participants),
* Daily doses of insulins,
* Safety and tolerability.
- Detailed Description
Approximately 41 weeks including a 26 week treatment period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 894
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lixisenatide Lixisenatide (AVE0010) Lixisenatide 10 mcg once daily (QD) for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. Lixisenatide Insulin Glargine (Mandatory background drug) Lixisenatide 10 mcg once daily (QD) for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. Lixisenatide Metformin (Background drug) Lixisenatide 10 mcg once daily (QD) for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. Insulin Glulisine QD Insulin glulisine QD Insulin glulisine QD from randomization up to Week 26 on top of Insulin glargine with or without metformin. Insulin Glulisine QD Insulin Glargine (Mandatory background drug) Insulin glulisine QD from randomization up to Week 26 on top of Insulin glargine with or without metformin. Insulin Glulisine QD Metformin (Background drug) Insulin glulisine QD from randomization up to Week 26 on top of Insulin glargine with or without metformin. Insulin Glulisine TID Insulin glulisine TID Insulin glulisine thrice daily (TID) from randomization up to Week 26 on top of Insulin glargine with or without metformin. Insulin Glulisine TID Insulin Glargine (Mandatory background drug) Insulin glulisine thrice daily (TID) from randomization up to Week 26 on top of Insulin glargine with or without metformin. Insulin Glulisine TID Metformin (Background drug) Insulin glulisine thrice daily (TID) from randomization up to Week 26 on top of Insulin glargine with or without metformin.
- Primary Outcome Measures
Name Time Method Change in HbA1c From Baseline to Week 26 Baseline, Week 26 Change in HbA1C was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using last on-treatment observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.
Change in Body Weight From Baseline to Week 26 Baseline, Week 26 Primary outcome was the comparison between Lixisenatide versus Insulin Glulisine TID.
Change in body weight was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With no Weight Gain at Week 26 Week 26 The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 3 days after the last dose of study drug.
Percentage of Participants With HbA1c Level <7% and ≤6.5% at Week 26 Week 26 The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Missing data was imputed using LOCF.
Change in Glucose Excursions From Baseline to Week 26 (in Participants Who Had an Injection of IMP Before Breakfast) Baseline, Week 26 Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change in glucose excursions was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug.
Percentage of Participants With Documented Symptomatic and Severe Symptomatic Hypoglycemia First dose of study drug up to 3 days after the last dose administration (maximum of 185 days) Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<60 mg/dL (3.3 mmol/L). Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the participant required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available.
Change in Average 7-point SMPG Profiles From Baseline to Week 26 Baseline, Week 26 Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime three times in a week before baseline, before visit Week 12 and before visit week 26 and the average value across the profiles performed in the week a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to the day of last dose of study drug.
Change in FPG From Baseline to Week 26 Baseline, Week 26 Change in FPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 1 day after the last dose of study drug.
Change in PPG From Baseline to Week 26 (in Participants Who Had an Injection of Investigational Medicinal Product [IMP] Before Breakfast) Baseline, Week 26 The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug.
Insulin Glulisine Dose at Week 26 Week 26 The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. Missing data was imputed using LOCF.
Change in Insulin Glargine Dose From Baseline to Week 26 Baseline, Week 26 Change in Insulin glargine dose was calculated by subtracting the baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug.
Total Insulin Dose at Week 26 Week 26 The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. Missing data was imputed using LOCF.
The outcome is reporting results of total insulin (amounts of Insulin Glargine plus Insulin Glulisine ) only for the arms in which Insulin Glulisine was administered and is not applicable for the lixisenatide arm in which only Insulin Glargine is administered. Change in dose of the insulin used by patients in the Lixisenatide arm (i.e. Insulin Glargine) is reported in the secondary Outcome Measure 9.Percentage of Participants Who Reached the Target of HbA1c <7%, Had no Weight Gain at Week 26, and Did Not Experience Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26-Week Treatment Period Week 26 The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for body weight assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug. Participants without post-baseline on-treatment values (HbA1c and body weight) that were no more than 30 days apart were counted as non-responders if at least one of the components (HbA1c and/or body weight) was available and showed non-response, or if they experienced at least one documented symptomatic hypoglycemia during the on-treatment period. Otherwise, they were counted as missing data.
Percentage of Participants Who Reached the Target of HbA1c <7% at Week 26 and Did Not Experienced Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26 Week Treatment Period Week 26 The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug.
Percentage of Participants Who Reached the Target of HbA1c <7% and Had no Weight Gain at Week 26 Week 26 The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for body weight assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug.
Trial Locations
- Locations (199)
Investigational Site Number 840030
🇺🇸Staten Island, New York, United States
Investigational Site Number 840042
🇺🇸Tempe, Arizona, United States
Investigational Site Number 840036
🇺🇸Nampa, Idaho, United States
Investigational Site Number 203105
🇨🇿Praha 4, Czech Republic
Investigational Site Number 203104
🇨🇿Trutnov, Czech Republic
Investigational Site Number 428105
🇱🇻Riga, Latvia
Investigational Site Number 428101
🇱🇻Sigulda, Latvia
Investigational Site Number 484108
🇲🇽Chihuahua, Mexico
Investigational Site Number 642103
🇷🇴Oradea, Romania
Investigational Site Number 642112
🇷🇴Pitesti, Romania
Investigational Site Number 642109
🇷🇴Targu Mures, Romania
Investigational Site Number 642101
🇷🇴Timisoara, Romania
Investigational Site Number 152105
🇨🇱Santiago, Chile
Investigational Site Number 152108
🇨🇱Santiago, Chile
Investigational Site Number 233102
🇪🇪Pärnu, Estonia
Investigational Site Number 233104
🇪🇪Tallinn, Estonia
Investigational Site Number 233101
🇪🇪Viljandimaa, Estonia
Investigational Site Number 428102
🇱🇻Riga, Latvia
Investigational Site Number 440104
🇱🇹Jonava, Lithuania
Investigational Site Number 440101
🇱🇹Kaunas, Lithuania
Investigational Site Number 484107
🇲🇽Guadalajara, Mexico
Investigational Site Number 484105
🇲🇽Guadalajara, Mexico
Investigational Site Number 484102
🇲🇽México, Mexico
Investigational Site Number 642105
🇷🇴Bacau, Romania
Investigational Site Number 642106
🇷🇴Deva, Romania
Investigational Site Number 484104
🇲🇽Guadalajara, Mexico
Investigational Site Number 152103
🇨🇱Santiago, Chile
Investigational Site Number 152101
🇨🇱Santiago, Chile
Investigational Site Number 152106
🇨🇱Santiago, Chile
Investigational Site Number 152109
🇨🇱Santiago, Chile
Investigational Site Number 203101
🇨🇿Ostrava 2, Czech Republic
Investigational Site Number 484109
🇲🇽Guadalajara, Mexico
Investigational Site Number 203107
🇨🇿Beroun, Czech Republic
Investigational Site Number 203103
🇨🇿Jilove U Prahy, Czech Republic
Investigational Site Number 203110
🇨🇿Police Nad Metuji, Czech Republic
Investigational Site Number 203102
🇨🇿Praha 4, Czech Republic
Investigational Site Number 203108
🇨🇿Praha 4, Czech Republic
Investigational Site Number 428104
🇱🇻Ogre, Latvia
Investigational Site Number 440103
🇱🇹Kaunas, Lithuania
Investigational Site Number 440102
🇱🇹Kaunas, Lithuania
Investigational Site Number 484101
🇲🇽Cuernavaca, Mexico
Investigational Site Number 484103
🇲🇽Mexico Df, Mexico
Investigational Site Number 484110
🇲🇽Guadalajara, Mexico
Investigational Site Number 642114
🇷🇴Ploiesti, Romania
Investigational Site Number 642111
🇷🇴Sibiu, Romania
Investigational Site Number 642107
🇷🇴Hunedoara, Romania
Investigational Site Number 642110
🇷🇴Targu Mures, Romania
Investigational Site Number 840012
🇺🇸Miami, Florida, United States
Investigational Site Number 840061
🇺🇸Miami, Florida, United States
Investigational Site Number 840049
🇺🇸Las Vegas, Nevada, United States
Investigational Site Number 840007
🇺🇸Oklahoma City, Oklahoma, United States
Investigational Site Number 840021
🇺🇸Pittsburgh, Pennsylvania, United States
Investigational Site Number 840033
🇺🇸Nashville, Tennessee, United States
Investigational Site Number 840020
🇺🇸Houston, Texas, United States
Investigational Site Number 642115
🇷🇴Timisoara, Romania
Investigational Site Number 643105
🇷🇺Moscow, Russian Federation
Investigational Site Number 804102
🇺🇦Vinnytsya, Ukraine
Investigational Site Number 804104
🇺🇦Chernivtsi, Ukraine
Investigational Site Number 826007
🇬🇧Carmarthen, United Kingdom
Investigational Site Number 804111
🇺🇦Zaporizhia, Ukraine
Investigational Site Number 643104
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 826009
🇬🇧Dundee, United Kingdom
Investigational Site Number 643109
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 643103
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 804103
🇺🇦Donetsk, Ukraine
Investigational Site Number 724105
🇪🇸La Coruña, Spain
Investigational Site Number 826005
🇬🇧Chester, United Kingdom
Investigational Site Number 826003
🇬🇧St Helens, United Kingdom
Investigational Site Number 124017
🇨🇦Newmarket, Canada
Investigational Site Number 124010
🇨🇦Toronto, Canada
Investigational Site Number 124005
🇨🇦Vancouver, Canada
Investigational Site Number 826011
🇬🇧Haddington, United Kingdom
Investigational Site Number 840041
🇺🇸Denver, Colorado, United States
Investigational Site Number 840010
🇺🇸Milwaukee, Wisconsin, United States
Investigational Site Number 840043
🇺🇸Sun City, Arizona, United States
Investigational Site Number 840003
🇺🇸Little Rock, Arkansas, United States
Investigational Site Number 840035
🇺🇸Santa Ana, California, United States
Investigational Site Number 840057
🇺🇸Northridge, California, United States
Investigational Site Number 840009
🇺🇸Evanston, Illinois, United States
Investigational Site Number 840024
🇺🇸Chicago, Illinois, United States
Investigational Site Number 840006
🇺🇸Wichita, Kansas, United States
Investigational Site Number 840026
🇺🇸Kalamazoo, Michigan, United States
Investigational Site Number 840060
🇺🇸Smithtown, New York, United States
Investigational Site Number 840029
🇺🇸New Hyde Park, New York, United States
Investigational Site Number 124018
🇨🇦Chatham, Canada
Investigational Site Number 124003
🇨🇦Red Deer, Canada
Investigational Site Number 152102
🇨🇱Santiago, Chile
Investigational Site Number 233103
🇪🇪Tallinn, Estonia
Investigational Site Number 250104
🇫🇷La Rochelle Cedex, France
Investigational Site Number 276118
🇩🇪Leipzig, Germany
Investigational Site Number 276109
🇩🇪St. Ingbert-Oberwürzbach, Germany
Investigational Site Number 348107
🇭🇺Budapest, Hungary
Investigational Site Number 348103
🇭🇺Pápa, Hungary
Investigational Site Number 428103
🇱🇻Jelgava, Latvia
Investigational Site Number 380103
🇮🇹Bologna, Italy
Investigational Site Number 380104
🇮🇹Torino, Italy
Investigational Site Number 348105
🇭🇺Zalaegerszeg, Hungary
Investigational Site Number 380105
🇮🇹Napoli, Italy
Investigational Site Number 484111
🇲🇽Durango, Mexico
Investigational Site Number 642102
🇷🇴Resita, Romania
Investigational Site Number 642116
🇷🇴Timisoara, Romania
Investigational Site Number 484106
🇲🇽Monterrey, Mexico
Investigational Site Number 616101
🇵🇱Bialystok, Poland
Investigational Site Number 616103
🇵🇱Bydgoszcz, Poland
Investigational Site Number 616106
🇵🇱Krakow, Poland
Investigational Site Number 616107
🇵🇱Warszawa, Poland
Investigational Site Number 616104
🇵🇱Krakow, Poland
Investigational Site Number 642108
🇷🇴Cluj Napoca, Romania
Investigational Site Number 616105
🇵🇱Pulawy, Poland
Investigational Site Number 642104
🇷🇴Oradea, Romania
Investigational Site Number 642117
🇷🇴Iasi, Romania
Investigational Site Number 250102
🇫🇷Paris Cedex 15, France
Investigational Site Number 250109
🇫🇷Mantes La Jolie, France
Investigational Site Number 250101
🇫🇷Vandoeuvre Les Nancy, France
Investigational Site Number 348102
🇭🇺Budapest, Hungary
Investigational Site Number 348104
🇭🇺Szeged, Hungary
Investigational Site Number 840031
🇺🇸La Mesa, California, United States
Investigational Site Number 840005
🇺🇸Mission Viejo, California, United States
Investigational Site Number 840037
🇺🇸Walnut Creek, California, United States
Investigational Site Number 840002
🇺🇸Temecula, California, United States
Investigational Site Number 840023
🇺🇸West Hills, California, United States
Investigational Site Number 840045
🇺🇸Lawrenceville, Georgia, United States
Investigational Site Number 840055
🇺🇸Avon, Indiana, United States
Investigational Site Number 840027
🇺🇸Des Moines, Iowa, United States
Investigational Site Number 840004
🇺🇸Avon, Indiana, United States
Investigational Site Number 840047
🇺🇸Lexington, Kentucky, United States
Investigational Site Number 840056
🇺🇸Paducah, Kentucky, United States
Investigational Site Number 840022
🇺🇸Marrero, Louisiana, United States
Investigational Site Number 840016
🇺🇸Baltimore, Maryland, United States
Investigational Site Number 840025
🇺🇸Buckley, Michigan, United States
Investigational Site Number 840048
🇺🇸Dearborn, Michigan, United States
Investigational Site Number 840017
🇺🇸Rockville, Maryland, United States
Investigational Site Number 840028
🇺🇸Fargo, North Dakota, United States
Investigational Site Number 840011
🇺🇸Salisbury, North Carolina, United States
Investigational Site Number 840052
🇺🇸Myrtle Beach, South Carolina, United States
Investigational Site Number 840032
🇺🇸Chattanooga, Tennessee, United States
Investigational Site Number 840034
🇺🇸Corpus Christi, Texas, United States
Investigational Site Number 840001
🇺🇸Dallas, Texas, United States
Investigational Site Number 840018
🇺🇸Norfolk, Virginia, United States
Investigational Site Number 840015
🇺🇸Salem, Virginia, United States
Investigational Site Number 124008
🇨🇦Brampton, Canada
Investigational Site Number 124015
🇨🇦Burlington, Canada
Investigational Site Number 124004
🇨🇦Coquitlam, Canada
Investigational Site Number 124014
🇨🇦Hamilton, Canada
Investigational Site Number 124016
🇨🇦Etobicoke, Canada
Investigational Site Number 124020
🇨🇦Montreal, Canada
Investigational Site Number 124011
🇨🇦Montreal, Canada
Investigational Site Number 124021
🇨🇦Quebec, Canada
Investigational Site Number 124002
🇨🇦Sherbrooke, Canada
Investigational Site Number 124012
🇨🇦St-Romuald, Canada
Investigational Site Number 124001
🇨🇦Toronto, Canada
Investigational Site Number 124006
🇨🇦Victoria, Canada
Investigational Site Number 152107
🇨🇱Santiago, Chile
Investigational Site Number 124007
🇨🇦Winnipeg, Canada
Investigational Site Number 250108
🇫🇷Bois Guillaume, France
Investigational Site Number 250105
🇫🇷Corbeil Essonnes, France
Investigational Site Number 250106
🇫🇷Lyon, France
Investigational Site Number 250107
🇫🇷Lyon, France
Investigational Site Number 250103
🇫🇷Venissieux, France
Investigational Site Number 276112
🇩🇪Bad Mergentheim, Germany
Investigational Site Number 276108
🇩🇪Berlin, Germany
Investigational Site Number 276102
🇩🇪Dortmund, Germany
Investigational Site Number 276106
🇩🇪Dresden, Germany
Investigational Site Number 276120
🇩🇪Dresden, Germany
Investigational Site Number 276117
🇩🇪Frankfurt A.M., Germany
Investigational Site Number 276113
🇩🇪Heidelberg, Germany
Investigational Site Number 276116
🇩🇪Görlitz, Germany
Investigational Site Number 276103
🇩🇪Neumünster, Germany
Investigational Site Number 276119
🇩🇪Magdeburg, Germany
Investigational Site Number 276115
🇩🇪Speyer, Germany
Investigational Site Number 348108
🇭🇺Budapest, Hungary
Investigational Site Number 348101
🇭🇺Eger, Hungary
Investigational Site Number 348106
🇭🇺Sátoraljaújhely, Hungary
Investigational Site Number 380102
🇮🇹Catania, Italy
Investigational Site Number 380101
🇮🇹Milano, Italy
Investigational Site Number 440105
🇱🇹Klaipeda, Lithuania
Investigational Site Number 642113
🇷🇴Galati, Romania
Investigational Site Number 643111
🇷🇺Moscow, Russian Federation
Investigational Site Number 643110
🇷🇺Penza, Russian Federation
Investigational Site Number 643102
🇷🇺Saratov, Russian Federation
Investigational Site Number 643107
🇷🇺Moscow, Russian Federation
Investigational Site Number 643108
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 643101
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 724103
🇪🇸Malaga, Spain
Investigational Site Number 643106
🇷🇺St. Petersburg, Russian Federation
Investigational Site Number 724102
🇪🇸El Ferrol, Spain
Investigational Site Number 724104
🇪🇸Sevilla, Spain
Investigational Site Number 804108
🇺🇦Mykolaiv, Ukraine
Investigational Site Number 826006
🇬🇧Ashton-Under-Lyne, United Kingdom
Investigational Site Number 826002
🇬🇧Birmingham, United Kingdom
Investigational Site Number 826008
🇬🇧Coventry, United Kingdom
Investigational Site Number 826001
🇬🇧Durham, United Kingdom
Investigational Site Number 826012
🇬🇧Leicester, United Kingdom
Investigational Site Number 826010
🇬🇧Plymouth, United Kingdom
Investigational Site Number 826004
🇬🇧Sheffield, United Kingdom
Investigational Site Number 804110
🇺🇦Odessa, Ukraine
Investigational Site Number 804105
🇺🇦Vinnytsya, Ukraine
Investigational Site Number 804107
🇺🇦Donetsk, Ukraine
Investigational Site Number 616102
🇵🇱Bytom, Poland