24-week Study Comparing Lixisenatide to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 Years
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Registration Number
- NCT00976937
- Lead Sponsor
- Sanofi
- Brief Summary
The purpose of this study is to evaluate benefits and risks of lixisenatide (AVE0010), in comparison to sitagliptin, as an add-on treatment to metformin, in obese (body mass index \[BMI\] greater than or equal to 30 kilogram per square meter \[kg/m\^2\]) type 2 diabetic patients less than 50 years of age, over a period of 24 weeks of treatment.
The primary objective of this study is to assess the efficacy of lixisenatide, in comparison to sitagliptin, as an add-on treatment to metformin on a composite endpoint of glycemic control in terms of glycosylated hemoglobin (HbA1c) and body weight, at Week 24.
Secondary objectives are to assess the effects of lixisenatide, in comparison to sitagliptin, as an add-on treatment to metformin on absolute changes in HbA1c values and body weight; fasting plasma glucose (FPG); plasma glucose, insulin, C-peptide, glucagon, and proinsulin during a 2-hour standardized meal test; insulin resistance assessed by homeostatic model assessment of insulin resistance (HOMA-IR); beta cell function assessed by homeostatic model assessment of beta-cell function (HOMA-beta); to evaluate safety, tolerability, and anti-lixisenatide antibody development.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 319
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sitagliptin Pen auto-injector Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo: sitagliptin 100 mg capsule orally QD up to Week 24 along with volume matching lixisenatide placebo 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24. Lixisenatide Metformin 2-step initiation regimen of lixisenatide along with sitagliptin placebo: lixisenatide 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24 along with placebo matching to sitagliptin 100 milligram (mg) capsule orally QD up to Week 24. Sitagliptin Lixisenatide Placebo Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo: sitagliptin 100 mg capsule orally QD up to Week 24 along with volume matching lixisenatide placebo 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24. Lixisenatide Lixisenatide (AVE0010) 2-step initiation regimen of lixisenatide along with sitagliptin placebo: lixisenatide 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24 along with placebo matching to sitagliptin 100 milligram (mg) capsule orally QD up to Week 24. Lixisenatide Pen auto-injector 2-step initiation regimen of lixisenatide along with sitagliptin placebo: lixisenatide 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24 along with placebo matching to sitagliptin 100 milligram (mg) capsule orally QD up to Week 24. Lixisenatide Sitagliptin Placebo 2-step initiation regimen of lixisenatide along with sitagliptin placebo: lixisenatide 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24 along with placebo matching to sitagliptin 100 milligram (mg) capsule orally QD up to Week 24. Sitagliptin Sitagliptin Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo: sitagliptin 100 mg capsule orally QD up to Week 24 along with volume matching lixisenatide placebo 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24. Sitagliptin Metformin Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo: sitagliptin 100 mg capsule orally QD up to Week 24 along with volume matching lixisenatide placebo 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24.
- Primary Outcome Measures
Name Time Method Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% and at Least 5% Weight Loss From Baseline at Week 24 Week 24 Percentage of patients who met both criteria (HbA1c \<7% at Week 24 and at least 5% weight loss from baseline at Week 24) is reported. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Insulin Resistance Assessed by Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) at Week 24 Baseline, Week 24 HOMA-IR was derived from FPG and FPI as: (FPI \[micro units per milliliter\]\*FPG \[mmol/L\]) divided by 22.5. Change was calculated for HOMA-IR by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Beta Cell Function Assessed by Homeostasis Model Assessment-Beta (HOMA-beta) at Week 24 Baseline, Week 24 HOMA-beta was derived from FPG and FPI as: (20\*FPI \[micro units/milliliter\]) divided by (FPG \[mmol/L\] minus 3.5). Change was calculated for HOMA-beta by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24 Week 24 The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Percentage of Patients Requiring Rescue Therapy During 24-Week Period Baseline up to Week 24 Routine fasting self-measured plasma glucose (SMPG) and central laboratory FPG (and HbA1c after week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after week 12) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG \>270 milligram/deciliter (mg/dL) (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG \>240 mg/dL (13.3 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8.5%.
Absolute Change From Baseline in HbA1c at Week 24 Baseline, Week 24 Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Body Weight at Week 24 Baseline, Week 24 Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) at Week 24 Baseline, Week 24 The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 Baseline, Week 24 Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Glucose Excursion at Week 24 Baseline, Week 24 Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting Plasma Insulin (FPI) and 2-hour Postprandial Plasma Insulin (PPI) at Week 24 Baseline, Week 24 Change was calculated for fasting plasma insulin and 2-hour post prandial plasma insulin by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting C-peptide and 2-hour Postprandial C-peptide at Week 24 Baseline, Week 24 Change was calculated for fasting C-peptide and 2-hour postprandial C-peptide by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting Glucagon and 2-hour Postprandial Glucagon at Week 24 Baseline, Week 24 Change was calculated for fasting glucagon and 2-hour postprandial glucagon by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting Proinsulin and 2-hour Postprandial Proinsulin at Week 24 Baseline, Week 24 Change was calculated for fasting proinsulin and 2-hour postprandial proinsulin by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of the study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Trial Locations
- Locations (92)
Sanofi-Aventis Investigational Site Number 840004
🇺🇸Medford, Oregon, United States
Sanofi-Aventis Investigational Site Number 840003
🇺🇸Muscle Shoals, Alabama, United States
Sanofi-Aventis Investigational Site Number 840006
🇺🇸Butte, Montana, United States
Sanofi-Aventis Investigational Site Number 840008
🇺🇸Dallas, Texas, United States
Sanofi-Aventis Investigational Site Number 840022
🇺🇸Mesa, Arizona, United States
Sanofi-Aventis Investigational Site Number 076002
🇧🇷Rio De Janeiro, Brazil
Sanofi-Aventis Investigational Site Number 320001
🇬🇹Guatemala, Guatemala
Sanofi-Aventis Investigational Site Number 840019
🇺🇸Montgomery, Alabama, United States
Sanofi-Aventis Investigational Site Number 124002
🇨🇦St-Romuald, Canada
Sanofi-Aventis Investigational Site Number 076005
🇧🇷Belem, Brazil
Sanofi-Aventis Investigational Site Number 076004
🇧🇷Sao Paulo, Brazil
Sanofi-Aventis Investigational Site Number 124013
🇨🇦Oakville, Canada
Sanofi-Aventis Investigational Site Number 152001
🇨🇱Santiago, Chile
Sanofi-Aventis Investigational Site Number 152004
🇨🇱Santiago, Chile
Sanofi-Aventis Investigational Site Number 036004
🇦🇺Elizabeth Vale, Australia
Sanofi-Aventis Investigational Site Number 124006
🇨🇦Montreal, Canada
Sanofi-Aventis Investigational Site Number 036002
🇦🇺Geelong, Australia
Sanofi-Aventis Investigational Site Number 124005
🇨🇦London, Canada
Sanofi-Aventis Investigational Site Number 036003
🇦🇺Sydney, Australia
Sanofi-Aventis Investigational Site Number 076007
🇧🇷Sao Paulo, Brazil
Sanofi-Aventis Investigational Site Number 076003
🇧🇷Curitiba, Brazil
Sanofi-Aventis Investigational Site Number 840014
🇺🇸Paramount, California, United States
Sanofi-Aventis Investigational Site Number 152003
🇨🇱Santiago, Chile
Sanofi-Aventis Investigational Site Number 616001
🇵🇱Bydgoszcz, Poland
Sanofi-Aventis Investigational Site Number 804004
🇺🇦Kyiv, Ukraine
Sanofi-Aventis Investigational Site Number 076006
🇧🇷Caxias Do Sul, Brazil
Sanofi-Aventis Investigational Site Number 036005
🇦🇺Meadowbrook, Australia
Sanofi-Aventis Investigational Site Number 152005
🇨🇱Santiago, Chile
Sanofi-Aventis Investigational Site Number 616003
🇵🇱Wroclaw, Poland
Sanofi-Aventis Investigational Site Number 804001
🇺🇦Kiev, Ukraine
Sanofi-Aventis Investigational Site Number 076001
🇧🇷Brasilia, Brazil
Sanofi-Aventis Investigational Site Number 124003
🇨🇦Vancouver, Canada
Sanofi-Aventis Investigational Site Number 036001
🇦🇺Box Hill, Australia
Sanofi-Aventis Investigational Site Number 124008
🇨🇦Hamilton, Canada
Sanofi-Aventis Investigational Site Number 642006
🇷🇴Bucuresti, Romania
Sanofi-Aventis Investigational Site Number 124004
🇨🇦Calgary, Canada
Sanofi-Aventis Investigational Site Number 124012
🇨🇦Thornhill, Canada
Sanofi-Aventis Investigational Site Number 124011
🇨🇦Toronto, Canada
Sanofi-Aventis Investigational Site Number 124007
🇨🇦Victoria, Canada
Sanofi-Aventis Investigational Site Number 320004
🇬🇹Guatemala, Guatemala
Sanofi-Aventis Investigational Site Number 320005
🇬🇹Guatemala, Guatemala
Sanofi-Aventis Investigational Site Number 604005
🇵🇪Lima, Peru
Sanofi-Aventis Investigational Site Number 152002
🇨🇱Santiago, Chile
Sanofi-Aventis Investigational Site Number 604001
🇵🇪Lima, Peru
Sanofi-Aventis Investigational Site Number 484006
🇲🇽Veracruz, Mexico
Sanofi-Aventis Investigational Site Number 484002
🇲🇽Zapopan, Mexico
Sanofi-Aventis Investigational Site Number 643001
🇷🇺St. Petersburg, Russian Federation
Sanofi-Aventis Investigational Site Number 840027
🇺🇸Redlands, California, United States
Sanofi-Aventis Investigational Site Number 840011
🇺🇸Anaheim, California, United States
Sanofi-Aventis Investigational Site Number 840007
🇺🇸Roswell, Georgia, United States
Sanofi-Aventis Investigational Site Number 840021
🇺🇸Augusta, Georgia, United States
Sanofi-Aventis Investigational Site Number 840018
🇺🇸Chicago, Illinois, United States
Sanofi-Aventis Investigational Site Number 840001
🇺🇸Evansville, Indiana, United States
Sanofi-Aventis Investigational Site Number 840016
🇺🇸Chicago, Illinois, United States
Sanofi-Aventis Investigational Site Number 840002
🇺🇸Baton Rouge, Louisiana, United States
Sanofi-Aventis Investigational Site Number 840020
🇺🇸Florissant, Missouri, United States
Sanofi-Aventis Investigational Site Number 840031
🇺🇸Clarkston, Michigan, United States
Sanofi-Aventis Investigational Site Number 840009
🇺🇸Brentwood, Tennessee, United States
Sanofi-Aventis Investigational Site Number 840026
🇺🇸Perrysburg, Ohio, United States
Sanofi-Aventis Investigational Site Number 840025
🇺🇸Altoona, Pennsylvania, United States
Sanofi-Aventis Investigational Site Number 840010
🇺🇸San Antonio, Texas, United States
Sanofi-Aventis Investigational Site Number 036006
🇦🇺Adelaide, Australia
Sanofi-Aventis Investigational Site Number 484012
🇲🇽Df, Mexico
Sanofi-Aventis Investigational Site Number 276005
🇩🇪Ludwigshafen, Germany
Sanofi-Aventis Investigational Site Number 320002
🇬🇹Guatemala, Guatemala
Sanofi-Aventis Investigational Site Number 276002
🇩🇪Berlin, Germany
Sanofi-Aventis Investigational Site Number 484003
🇲🇽Aguascalientes, Mexico
Sanofi-Aventis Investigational Site Number 276004
🇩🇪Schkeuditz, Germany
Sanofi-Aventis Investigational Site Number 320006
🇬🇹Guatemala, Guatemala
Sanofi-Aventis Investigational Site Number 484010
🇲🇽Chihuahua, Mexico
Sanofi-Aventis Investigational Site Number 484009
🇲🇽Chihuahua, Mexico
Sanofi-Aventis Investigational Site Number 484008
🇲🇽Merida, Mexico
Sanofi-Aventis Investigational Site Number 484011
🇲🇽México City, Mexico
Sanofi-Aventis Investigational Site Number 604003
🇵🇪Lima, Peru
Sanofi-Aventis Investigational Site Number 484001
🇲🇽Pachuca, Mexico
Sanofi-Aventis Investigational Site Number 484005
🇲🇽Pachuca, Mexico
Sanofi-Aventis Investigational Site Number 604004
🇵🇪Lima, Peru
Sanofi-Aventis Investigational Site Number 604002
🇵🇪Lima, Peru
Sanofi-Aventis Investigational Site Number 616006
🇵🇱Warszawa, Poland
Sanofi-Aventis Investigational Site Number 616002
🇵🇱Bialystok, Poland
Sanofi-Aventis Investigational Site Number 642004
🇷🇴Bacau, Romania
Sanofi-Aventis Investigational Site Number 642010
🇷🇴Iasi, Romania
Sanofi-Aventis Investigational Site Number 642008
🇷🇴Bucuresti, Romania
Sanofi-Aventis Investigational Site Number 642005
🇷🇴Suceava, Romania
Sanofi-Aventis Investigational Site Number 642009
🇷🇴Ploiesti, Romania
Sanofi-Aventis Investigational Site Number 642001
🇷🇴Resita, Romania
Sanofi-Aventis Investigational Site Number 643002
🇷🇺Kazan, Russian Federation
Sanofi-Aventis Investigational Site Number 642007
🇷🇴Timisoara, Romania
Sanofi-Aventis Investigational Site Number 643003
🇷🇺St-Petersburg, Russian Federation
Sanofi-Aventis Investigational Site Number 643005
🇷🇺St-Petersburg, Russian Federation
Sanofi-Aventis Investigational Site Number 804003
🇺🇦Chernivtsi, Ukraine
Sanofi-Aventis Investigational Site Number 643004
🇷🇺Tyumen, Russian Federation