Efficacy and Safety of Insulin Glargine/ Lixisenatide Fixed Ratio Combination Compared to Insulin Glargine Alone and Lixisenatide Alone on Top of Metformin in Patients With T2DM
- Conditions
- Type 2 Diabetes
- Interventions
- Drug: Insulin glargine/lixisenatide Fixed Ratio CombinationDrug: Insulin glargine (HOE901)
- Registration Number
- NCT02058147
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To compare the insulin glargine/lixisenatide fixed ratio combination to lixisenatide alone and to insulin glargine alone (on top of metformin treatment) in glycated hemoglobin (HbA1c) change from baseline to Week 30.
Secondary Objective:
To compare the overall efficacy and safety of insulin glargine/lixisenatide fixed ratio combination (FRC) to insulin glargine alone and to lixisenatide alone (on top of metformin treatment) over a 30 week treatment period in participants with type 2 diabetes.
- Detailed Description
Approximately 37 weeks including up to 6 weeks of screening, 30-week treatment period, and a 3 days follow-up period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1170
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 Fixed Ratio Combination FRC once daily (QD) for 30 weeks. Dose individually adjusted. Insulin Glargine Insulin glargine (HOE901) Insulin glargine QD for 30 weeks. Dose individually adjusted. Insulin Glargine Metformin Insulin glargine QD for 30 weeks. Dose individually adjusted. Lixisenatide Lixisenatide (AVE0010) Lixisenatide 10 mcg QD for 2 weeks, then 20 mcg QD (maintenance dose). Lixisenatide Metformin Lixisenatide 10 mcg QD for 2 weeks, then 20 mcg QD (maintenance dose). Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) Metformin FRC once daily (QD) for 30 weeks. Dose individually adjusted.
- Primary Outcome Measures
Name Time Method Change in HbA1c From Baseline to Week 30 Baseline, Week 30 Primary outcome was to test superiority of FRC versus Lixisenatide and non-inferiority versus Insulin glargine.
Change in HbA1c was calculated by subtracting baseline value from Week 30 value.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With HbA1c <7.0% or ≤6.5% at Week 30 Week 30 Participants without Week 30 value for HbA1c were counted as non-responders.
Change in Plasma Glucose Excursion From Baseline to Week 30 Baseline, Week 30 Plasma glucose excursion = 2-hour postprandial plasma glucose (PPG) value minus plasma glucose value obtained 30 minutes prior to the start of meal and before investigational medicinal product (IMP) administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 30 value. Missing data was imputed using last observation carried forward (LOCF).
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.
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 30 Baseline, Week 30 Change in FPG 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 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).
Average Daily Insulin Glargine Dose at Week 30 Week 30 The analysis included scheduled measurements obtained up to the date of last injection of the IMP, including those obtained after introduction of rescue therapy.
Change in 2-Hour Postprandial Plasma Glucose (PPG) From Baseline to Week 30 Baseline, Week 30 The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 30 value. Missing data was imputed using LOCF.
Percentage of Participants Reaching HbA1c <7.0% at Week 30 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). The analysis included all HbA1c measurements at Week 30, including those obtained after the IMP discontinuation or the introduction of rescue medication.
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) was 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) Documented symptomatic hypoglycemia was an event during which 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) Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤ 70 mg/dL (3.9 mmol/L).
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) 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 have 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 of injury to themselves or others.
Trial Locations
- Locations (273)
Investigational Site Number 840027
🇺🇸Phoenix, Arizona, United States
Investigational Site Number 840122
🇺🇸Phoenix, Arizona, United States
Investigational Site Number 840062
🇺🇸Tempe, Arizona, United States
Investigational Site Number 840023
🇺🇸Tempe, Arizona, United States
Investigational Site Number 840084
🇺🇸Little Rock, Arkansas, United States
Investigational Site Number 840100
🇺🇸Anaheim, California, United States
Investigational Site Number 840065
🇺🇸Bell Gardens, California, United States
Investigational Site Number 840090
🇺🇸Chino, California, United States
Investigational Site Number 840002
🇺🇸Chula Vista, California, United States
Investigational Site Number 840013
🇺🇸Concord, California, United States
Scroll for more (263 remaining)Investigational Site Number 840027🇺🇸Phoenix, Arizona, United States