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 840607
🇺🇸Birmingham, Alabama, United States
Investigational Site Number 840570
🇺🇸Sun City, Arizona, United States
Investigational Site Number 840562
🇺🇸Tempe, Arizona, United States
Investigational Site Number 840577
🇺🇸Tucson, Arizona, United States
Investigational Site Number 840517
🇺🇸Little Rock, Arkansas, United States
Investigational Site Number 840537
🇺🇸Little Rock, Arkansas, United States
Investigational Site Number 840568
🇺🇸Bell Gardens, California, United States
Investigational Site Number 840550
🇺🇸Chino, California, United States
Investigational Site Number 840529
🇺🇸Chula Vista, California, United States
Investigational Site Number 840623
🇺🇸Corona, California, United States
Scroll for more (226 remaining)Investigational Site Number 840607🇺🇸Birmingham, Alabama, United States