24-week Treatment With Lixisenatide in Type 2 Diabetes Insufficiently Controlled With Metformin and Insulin Glargine
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Drug: Lixisenatide (AVE0010)Drug: PlaceboDrug: Insulin glargineDevice: Pen auto-injectorDrug: MetforminDrug: Thiazolidinedione (TZD)
- Registration Number
- NCT00975286
- Lead Sponsor
- Sanofi
- Brief Summary
The purpose of the study is to evaluate the benefits and risks of lixisenatide (AVE0010), in comparison to placebo, as an add-on treatment to insulin glargine and metformin with or without thiazolidinediones (TZDs), over a period of 24 weeks of treatment.
The primary objective is to assess the effects of lixisenatide in comparison to placebo, when added to insulin glargine and metformin, on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.
The secondary objectives are to assess the effects of lixisenatide on the percentage of patients reaching HbA1c less than (\<) 7 percent (%) and less than or equal to (\<=) 6.5%, plasma glucose (fasting, postprandial during a standardized meal challenge test, 7-point self monitored profiles), body weight, insulin glargine doses, to evaluate safety and tolerability (including anti-lixisenatide antibody assessment), and to assess the impact on treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (state) (DTSQs) in the participating countries where it is validated.
- Detailed Description
The study comprises 3 periods:
* An up to 14-week screening period, which includes an up to 2-week screening phase and a 12-week run-in phase with introduction and titration of insulin glargine on top of metformin +/-TZDs.
* At the end of the run-in phase, patients whose HbA1c (centralized assay) is greater than or equal to (\>=) 7% and less than or equal to (\<=) 9% and whose mean fasting self-monitored plasma glucose (SMPG) calculated from the self measurements for the 7 days prior to Visit 12 (Week -1) is \<=140 milligram per deciliter (mg/dL) (7.8 millimole per liter \[mmol/L\]), would enter a 24-week double-blind randomized treatment period comparing lixisenatide to placebo (on top of insulin glargine + metformin +/- TZDs).
* A 3-day safety follow up period.
Maximum duration is of 39 weeks +/- 7 days.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 446
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lixisenatide Lixisenatide (AVE0010) 2-step initiation regimen of 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. Lixisenatide Pen auto-injector 2-step initiation regimen of 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. Lixisenatide Thiazolidinedione (TZD) 2-step initiation regimen of 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. Placebo Placebo 2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24. Placebo Pen auto-injector 2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24. Placebo Thiazolidinedione (TZD) 2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24. Lixisenatide Insulin glargine 2-step initiation regimen of 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. Lixisenatide Metformin 2-step initiation regimen of 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. Placebo Insulin glargine 2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24. Placebo Metformin 2-step initiation regimen of volume matching 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 Absolute Change From Baseline in Glycosylated Hemoglobin (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 14 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
- Secondary Outcome Measures
Name Time Method 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. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Change From Baseline in Average Insulin Glargine Daily Dose at Week 24 Baseline, Week 24 Change was calculated 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. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
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. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% 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 14 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
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 14 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Percentage of Patients Requiring Rescue Therapy During the Double-blind Period Baseline up to Week 24 Routine fasting SMPG, central laboratory FPG and HbA1c 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 were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG \>200 milligram/deciliter (mg/dL) (11.1 mmol/L) or HbA1c \>9%, from Week 8 to Week 24: fasting SMPG/FPG \>180 mg/dL (10.0 mmol/L) or HbA1c \>8.5%. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Change From Baseline in Treatment Satisfaction Score (Sum of Items 1, 4, 5, 6, 7 and 8 of DTSQ) at Week 24 Baseline, Week 24 Change was calculated by subtracting baseline value from Week 24 value. DTSQ: 8-item questionnaire to assess treatment satisfaction and patient perception of hyper and hypoglycemia. Each question (Q) scored on a Likert scale from 0 to 6. Six items (Q1 and 4-8; higher score = more satisfaction) measured treatment satisfaction and were summed to calculate treatment satisfaction score which ranged from 0 (very dissatisfied) to 36 (very satisfied). Two items (Q2 and 3), which were not included, measured perceived hyperglycemia and hypoglycemia, respectively and lower scores represented good perceived blood glucose control. 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. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
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 study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
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 study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Change From Baseline in Average 7-Point Self Monitored Plasma Glucose (SMPG) Profile at Week 24 Baseline, Week 24 Patients recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime once in a week and the average value for the 7-time points was calculated. 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. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Trial Locations
- Locations (140)
Sanofi-Aventis Investigational Site Number 840210
🇺🇸Dallas, Texas, United States
Sanofi-Aventis Investigational Site Number 840211
🇺🇸Baton Rouge, Louisiana, United States
Sanofi-Aventis Investigational Site Number 840230
🇺🇸Hyattsville, Maryland, United States
Sanofi-Aventis Investigational Site Number 208201
🇩🇰København Nv, Denmark
Sanofi-Aventis Investigational Site Number 124218
🇨🇦Thornhill, Canada
Sanofi-Aventis Investigational Site Number 276204
🇩🇪St. Ingbert-Oberwürzbach, Germany
Sanofi-Aventis Investigational Site Number 840222
🇺🇸Portland, Oregon, United States
Sanofi-Aventis Investigational Site Number 840212
🇺🇸Mountain Home, Arkansas, United States
Sanofi-Aventis Investigational Site Number 840214
🇺🇸Greenbrae, California, United States
Sanofi-Aventis Investigational Site Number 840202
🇺🇸Philadelphia, Pennsylvania, United States
Sanofi-Aventis Investigational Site Number 124213
🇨🇦Chatham, Canada
Sanofi-Aventis Investigational Site Number 484205
🇲🇽Tlalnepantla, Mexico
Sanofi-Aventis Investigational Site Number 804202
🇺🇦Kyiv, Ukraine
Sanofi-Aventis Investigational Site Number 616203
🇵🇱Zabrze, Poland
Sanofi-Aventis Investigational Site Number 752201
🇸🇪Stockholm, Sweden
Sanofi-Aventis Investigational Site Number 642207
🇷🇴Timisoara, Romania
Sanofi-Aventis Investigational Site Number 158202
🇨🇳Tainan Hsien, Taiwan
Sanofi-Aventis Investigational Site Number 804203
🇺🇦Chernivtsi, Ukraine
Sanofi-Aventis Investigational Site Number 804205
🇺🇦Kyiv, Ukraine
Sanofi-Aventis Investigational Site Number 804204
🇺🇦Vinnytsya, Ukraine
Sanofi-Aventis Investigational Site Number 356208
🇮🇳Indore, India
Sanofi-Aventis Investigational Site Number 642203
🇷🇴Iasi, Romania
Sanofi-Aventis Investigational Site Number 642202
🇷🇴Oradea, Romania
Sanofi-Aventis Investigational Site Number 376201
🇮🇱Holon, Israel
Sanofi-Aventis Investigational Site Number 642208
🇷🇴Bucharest, Romania
Sanofi-Aventis Investigational Site Number 840206
🇺🇸Hot Springs, Arkansas, United States
Sanofi-Aventis Investigational Site Number 840223
🇺🇸Mesa, Arizona, United States
Sanofi-Aventis Investigational Site Number 840201
🇺🇸Little Rock, Arkansas, United States
Sanofi-Aventis Investigational Site Number 840221
🇺🇸Orlando, Florida, United States
Sanofi-Aventis Investigational Site Number 840215
🇺🇸Concord, California, United States
Sanofi-Aventis Investigational Site Number 840209
🇺🇸Rockville, Maryland, United States
Sanofi-Aventis Investigational Site Number 840219
🇺🇸Brighton, Michigan, United States
Sanofi-Aventis Investigational Site Number 840231
🇺🇸Sea Girt, New Jersey, United States
Sanofi-Aventis Investigational Site Number 840225
🇺🇸Mentor, Ohio, United States
Sanofi-Aventis Investigational Site Number 840208
🇺🇸Fargo, North Dakota, United States
Sanofi-Aventis Investigational Site Number 840229
🇺🇸Bristol, Tennessee, United States
Sanofi-Aventis Investigational Site Number 840205
🇺🇸Germantown, Tennessee, United States
Sanofi-Aventis Investigational Site Number 840228
🇺🇸Houston, Texas, United States
Sanofi-Aventis Investigational Site Number 840213
🇺🇸Plano, Texas, United States
Sanofi-Aventis Investigational Site Number 840217
🇺🇸Houston, Texas, United States
Sanofi-Aventis Investigational Site Number 840227
🇺🇸Norfolk, Virginia, United States
Sanofi-Aventis Investigational Site Number 032204
🇦🇷Buenos Aires, Argentina
Sanofi-Aventis Investigational Site Number 032205
🇦🇷Capital Federal, Argentina
Sanofi-Aventis Investigational Site Number 032201
🇦🇷Capital Federal, Argentina
Sanofi-Aventis Investigational Site Number 032209
🇦🇷Capital Federal, Argentina
Sanofi-Aventis Investigational Site Number 032211
🇦🇷Corrientes, Argentina
Sanofi-Aventis Investigational Site Number 032202
🇦🇷Parana, Argentina
Sanofi-Aventis Investigational Site Number 032203
🇦🇷Rosario, Argentina
Sanofi-Aventis Investigational Site Number 076207
🇧🇷Belem, Brazil
Sanofi-Aventis Investigational Site Number 076202
🇧🇷Brasilia, Brazil
Sanofi-Aventis Investigational Site Number 076204
🇧🇷Sao Paulo, Brazil
Sanofi-Aventis Investigational Site Number 076205
🇧🇷Porto Alegre, Brazil
Sanofi-Aventis Investigational Site Number 124219
🇨🇦Brampton, Canada
Sanofi-Aventis Investigational Site Number 124215
🇨🇦Etobicoke, Canada
Sanofi-Aventis Investigational Site Number 124202
🇨🇦Red Deer, Canada
Sanofi-Aventis Investigational Site Number 124208
🇨🇦Chilliwack, Canada
Sanofi-Aventis Investigational Site Number 124205
🇨🇦Quebec, Canada
Sanofi-Aventis Investigational Site Number 124201
🇨🇦Toronto, Canada
Sanofi-Aventis Investigational Site Number 356210
🇮🇳Ahmedabad, India
Sanofi-Aventis Investigational Site Number 124217
🇨🇦Winnipeg, Canada
Sanofi-Aventis Investigational Site Number 124207
🇨🇦Toronto, Canada
Sanofi-Aventis Investigational Site Number 124209
🇨🇦Victoria, Canada
Sanofi-Aventis Investigational Site Number 152202
🇨🇱Santiago, Chile
Sanofi-Aventis Investigational Site Number 152201
🇨🇱Santiago, Chile
Sanofi-Aventis Investigational Site Number 152203
🇨🇱Santiago, Chile
Sanofi-Aventis Investigational Site Number 152204
🇨🇱Santiago, Chile
Sanofi-Aventis Investigational Site Number 203204
🇨🇿Praha 5, Czech Republic
Sanofi-Aventis Investigational Site Number 208202
🇩🇰Frederiksberg, Denmark
Sanofi-Aventis Investigational Site Number 208205
🇩🇰Slagelse, Denmark
Sanofi-Aventis Investigational Site Number 233201
🇪🇪Pärnu, Estonia
Sanofi-Aventis Investigational Site Number 356205
🇮🇳Chennai, India
Sanofi-Aventis Investigational Site Number 233203
🇪🇪Tallinn, Estonia
Sanofi-Aventis Investigational Site Number 233202
🇪🇪Viljandimaa, Estonia
Sanofi-Aventis Investigational Site Number 250206
🇫🇷La Rochelle Cedex, France
Sanofi-Aventis Investigational Site Number 250204
🇫🇷Amiens Cedex 1, France
Sanofi-Aventis Investigational Site Number 250203
🇫🇷Le Creusot, France
Sanofi-Aventis Investigational Site Number 250201
🇫🇷Nantes, France
Sanofi-Aventis Investigational Site Number 348207
🇭🇺Budapest, Hungary
Sanofi-Aventis Investigational Site Number 348205
🇭🇺Balatonfüred, Hungary
Sanofi-Aventis Investigational Site Number 348202
🇭🇺Budapest, Hungary
Sanofi-Aventis Investigational Site Number 250202
🇫🇷Pierre Benite, France
Sanofi-Aventis Investigational Site Number 276201
🇩🇪Dresden, Germany
Sanofi-Aventis Investigational Site Number 276202
🇩🇪Mainz, Germany
Sanofi-Aventis Investigational Site Number 348203
🇭🇺Szeged, Hungary
Sanofi-Aventis Investigational Site Number 348204
🇭🇺Debrecen, Hungary
Sanofi-Aventis Investigational Site Number 348206
🇭🇺Gyula, Hungary
Sanofi-Aventis Investigational Site Number 348201
🇭🇺Zalaegerszeg, Hungary
Sanofi-Aventis Investigational Site Number 356202
🇮🇳Bangalore, India
Sanofi-Aventis Investigational Site Number 356201
🇮🇳Belgaum, India
Sanofi-Aventis Investigational Site Number 376202
🇮🇱Haifa, Israel
Sanofi-Aventis Investigational Site Number 356203
🇮🇳Karnal, India
Sanofi-Aventis Investigational Site Number 356207
🇮🇳Kochi, India
Sanofi-Aventis Investigational Site Number 380201
🇮🇹Milano, Italy
Sanofi-Aventis Investigational Site Number 376204
🇮🇱Kfar Saba, Israel
Sanofi-Aventis Investigational Site Number 376203
🇮🇱Tel Hashomer, Israel
Sanofi-Aventis Investigational Site Number 458203
🇲🇾Kelantan, Malaysia
Sanofi-Aventis Investigational Site Number 380202
🇮🇹Perugia, Italy
Sanofi-Aventis Investigational Site Number 458202
🇲🇾Kuala Lumpur, Malaysia
Sanofi-Aventis Investigational Site Number 484206
🇲🇽México City, Mexico
Sanofi-Aventis Investigational Site Number 484204
🇲🇽Durango, Mexico
Sanofi-Aventis Investigational Site Number 484201
🇲🇽Cuernavaca, Mexico
Sanofi-Aventis Investigational Site Number 484203
🇲🇽Guadalajara, Mexico
Sanofi-Aventis Investigational Site Number 528202
🇳🇱Groningen, Netherlands
Sanofi-Aventis Investigational Site Number 528203
🇳🇱Amsterdam, Netherlands
Sanofi-Aventis Investigational Site Number 528204
🇳🇱Zwijndrecht, Netherlands
Sanofi-Aventis Investigational Site Number 616206
🇵🇱Plock, Poland
Sanofi-Aventis Investigational Site Number 616205
🇵🇱Sopot, Poland
Sanofi-Aventis Investigational Site Number 616201
🇵🇱Szczecin, Poland
Sanofi-Aventis Investigational Site Number 840216
🇵🇷San Juan, Puerto Rico
Sanofi-Aventis Investigational Site Number 642205
🇷🇴Deva, Romania
Sanofi-Aventis Investigational Site Number 840226
🇵🇷Ponce, Puerto Rico
Sanofi-Aventis Investigational Site Number 642204
🇷🇴Brasov, Romania
Sanofi-Aventis Investigational Site Number 643203
🇷🇺Saratov, Russian Federation
Sanofi-Aventis Investigational Site Number 642201
🇷🇴Timisoara, Romania
Sanofi-Aventis Investigational Site Number 752205
🇸🇪Luleå, Sweden
Sanofi-Aventis Investigational Site Number 710203
🇿🇦Pretoria, South Africa
Sanofi-Aventis Investigational Site Number 710201
🇿🇦Durban, South Africa
Sanofi-Aventis Investigational Site Number 643202
🇷🇺St. Petersburg, Russian Federation
Sanofi-Aventis Investigational Site Number 752204
🇸🇪Göteborg, Sweden
Sanofi-Aventis Investigational Site Number 710202
🇿🇦Cape Town, South Africa
Sanofi-Aventis Investigational Site Number 752203
🇸🇪Härnösand, Sweden
Sanofi-Aventis Investigational Site Number 752202
🇸🇪Malmö, Sweden
Sanofi-Aventis Investigational Site Number 158203
🇨🇳Taichung, Taiwan
Sanofi-Aventis Investigational Site Number 158204
🇨🇳Changhua, Taiwan
Sanofi-Aventis Investigational Site Number 158201
🇨🇳Taichung R.O.C., Taiwan
Sanofi-Aventis Investigational Site Number 170202
🇨🇴Bogota, Colombia
Sanofi-Aventis Investigational Site Number 170201
🇨🇴Bogota, Colombia
Sanofi-Aventis Investigational Site Number 203202
🇨🇿Hradec Kralove, Czech Republic
Sanofi-Aventis Investigational Site Number 233204
🇪🇪Tartu, Estonia
Sanofi-Aventis Investigational Site Number 152206
🇨🇱Santiago, Chile
Sanofi-Aventis Investigational Site Number 152205
🇨🇱Santiago, Chile
Sanofi-Aventis Investigational Site Number 356206
🇮🇳Bangalore, India
Sanofi-Aventis Investigational Site Number 616208
🇵🇱Lubin, Poland
Sanofi-Aventis Investigational Site Number 616207
🇵🇱Pulawy, Poland
Sanofi-Aventis Investigational Site Number 170204
🇨🇴Barranquilla, Colombia
Sanofi-Aventis Investigational Site Number 616202
🇵🇱Krakow, Poland
Sanofi-Aventis Investigational Site Number 642206
🇷🇴Targu Mures, Romania
Sanofi-Aventis Investigational Site Number 356204
🇮🇳Bangalore, India
Sanofi-Aventis Investigational Site Number 356209
🇮🇳Nagpur, India
Sanofi-Aventis Investigational Site Number 804201
🇺🇦Kiev, Ukraine