Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Registration Number
- NCT01169779
- Lead Sponsor
- Sanofi
- Brief Summary
The purpose of this study is to evaluate the benefits and risks of lixisenatide (AVE0010) in comparison to placebo, as an add-on treatment to metformin with or without sulfonylurea, over a period of 24 weeks of treatment.
The primary objective is to assess the effects on glycemic control of lixisenatide (AVE0010) in comparison to placebo as an add-on treatment to metformin with or without sulfonylurea in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.
The secondary objectives are to assess the effects of lixisenatide over 24 weeks on percentage of patients reaching HbA1c less than (\< ) 7 percent (%) or HbA1c less than or equal to (\<=) 6.5%, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG) and glucose excursion during standardized meal test, body weight; to evaluate safety, tolerability, pharmacokinetic (PK) and anti-lixisenatide antibody development.
- Detailed Description
The study duration for each patient is 27 weeks +/- 10 days (up to 2 weeks screening + 1 week run-in + 24 weeks double-blind treatment + 3 days follow-up).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 391
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lixisenatide Pen auto-injector 1-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 2 weeks, followed by 20 mcg QD up to Week 24. Lixisenatide Lixisenatide (AVE0010) 1-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 2 weeks, followed by 20 mcg QD up to Week 24. Placebo Placebo 1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, followed by 20 mcg QD up to Week 24. Lixisenatide Sulfonylurea 1-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 2 weeks, followed by 20 mcg QD up to Week 24. Placebo Pen auto-injector 1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, followed by 20 mcg QD up to Week 24. Placebo Sulfonylurea 1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, followed by 20 mcg QD up to Week 24. Lixisenatide Metformin 1-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 2 weeks, followed by 20 mcg QD up to Week 24. Placebo Metformin 1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, followed by 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 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 on-treatment assessment for at least 1 efficacy variable, were required.
- Secondary Outcome Measures
Name Time Method 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 on-treatment 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 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 on-treatment 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.
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 on-treatment 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 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 on-treatment 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.
Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period Baseline up to Week 24 Routine fasting self-monitored 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 \>250 milligram/deciliter (mg/dL) (13.9 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG \>220 mg/dL (12.2 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8.5%. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
Trial Locations
- Locations (35)
Investigational Site Number 156009
🇨🇳Beijing, China
Investigational Site Number 156016
🇨🇳Changsha, China
Investigational Site Number 156015
🇨🇳Changsha, China
Investigational Site Number 156006
🇨🇳Chengdu, China
Investigational Site Number 156032
🇨🇳Chengdu, China
Investigational Site Number 156008
🇨🇳Guangzhou, China
Investigational Site Number 156025
🇨🇳Guangzhou, China
Investigational Site Number 156029
🇨🇳Hefei, China
Investigational Site Number 156013
🇨🇳Qingdao, China
Investigational Site Number 156007
🇨🇳Shanghai, China
Investigational Site Number 156020
🇨🇳Shenyang, China
Investigational Site Number 156037
🇨🇳Tianjin, China
Investigational Site Number 156011
🇨🇳Beijing, China
Investigational Site Number 156002
🇨🇳Beijing, China
Investigational Site Number 156012
🇨🇳Beijing, China
Investigational Site Number 156019
🇨🇳Beijing, China
Investigational Site Number 156001
🇨🇳Beijing, China
Investigational Site Number 156036
🇨🇳Changchun, China
Investigational Site Number 156003
🇨🇳Beijing, China
Investigational Site Number 156010
🇨🇳Dalian, China
Investigational Site Number 156004
🇨🇳Guangzhou, China
Investigational Site Number 156031
🇨🇳Haikou, China
Investigational Site Number 156014
🇨🇳Harbin, China
Investigational Site Number 156035
🇨🇳Suzhou, China
Investigational Site Number 156030
🇨🇳Shanghai, China
Investigational Site Number 156033
🇨🇳Taiyuan, China
Investigational Site Number 156022
🇨🇳Xi'An, China
Investigational Site Number 156023
🇨🇳Xi'An, China
Investigational Site Number 344003
🇭🇰Hong Kong, Hong Kong
Investigational Site Number 344001
🇭🇰Hong Kong, Hong Kong
Investigational Site Number 458001
🇲🇾Kelantan, Malaysia
Investigational Site Number 458002
🇲🇾Putrajaya, Malaysia
Investigational Site Number 764002
🇹🇭Bangkok, Thailand
Investigational Site Number 458003
🇲🇾Kuala Lumpur, Malaysia
Investigational Site Number 344002
🇭🇰Shatin, Nt, Hong Kong