An Open-label, Randomized, Three-parallel-group Study on Pharmacodynamic Effects of 8-week QD Treatment With Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 142
- 试验地点
- 8
- 主要终点
- Change From Baseline to Day 56 in Plasma Glucose Corrected Area Under The Plasma Concentration-Time Curve (AUC) From Time 0.5 Hours to 4.5 Hours
研究概览
简要总结
Primary Objective:
- To investigate the effects of repeated subcutaneous doses of lixisenatide 20 μg once daily (QD) as compared to liraglutide 1.2 mg QD or 1.8 mg QD in reducing post-prandial plasma glucose (PPG) assessed as area under the plasma glucose-concentration-time curve (AUC) after a standardized breakfast at the end of a 8-week treatment period in participants with type 2 diabetes mellitus (T2DM) not adequately controlled with insulin glargine (± metformin).
Secondary Objectives:
-
To assess the effects of lixisenatide 20 μg QD as compared to liraglutide 1.2 QD or 1.8 mg QD after an 8-week treatment period in participants with T2DM not adequately controlled with insulin glargine (± metformin) on:
-
Post-prandial C-peptide, glucagon and appetite perceptions after a standardized breakfast,
-
Appetite perceptions after standardized dinner,
-
Gastric emptying after a standardized labelled test meal,
-
Fasting plasma glucose, 24-hour plasma glucose profile,
-
Glycosylated hemoglobin (HbA1c),
-
Insulin glargine dose,
-
7-point self monitored plasma glucose (SMPG),
-
Body weight and waist circumference,
-
24-hour heart rate and blood pressure,
-
To assess lixisenatide and liraglutide safety and tolerability as add on treatment to insulin glargine (± metformin).
详细描述
Up to 2-week screening period
- A run-in period of 12 weeks at maximum including a forced titration with insulin glargine up to 11 weeks and 1 baseline pharmacodynamic assessment week
- A 8-week treatment(s) period(s) up to Day 57
- Follow-up: 7 ±2 days after the last treatment day
- Total study duration approximately 14 weeks up to 23 weeks
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Lixisenatide 20 μg
Subcutaneous injection of lixisenatide10 μg once daily (QD) for 2 weeks followed by 20 μg QD for 6 weeks under fasted conditions, on top of insulin glargine with or without metformin.
干预措施: Lixisenatide (AVE0010) (Drug)
Lixisenatide 20 μg
Subcutaneous injection of lixisenatide10 μg once daily (QD) for 2 weeks followed by 20 μg QD for 6 weeks under fasted conditions, on top of insulin glargine with or without metformin.
干预措施: Insulin Glargine (Drug)
Lixisenatide 20 μg
Subcutaneous injection of lixisenatide10 μg once daily (QD) for 2 weeks followed by 20 μg QD for 6 weeks under fasted conditions, on top of insulin glargine with or without metformin.
干预措施: Metformin (Drug)
Liraglutide 1.2 mg
Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks under fasted conditions, on top of insulin glargine with or without metformin.
干预措施: Liraglutide (Drug)
Liraglutide 1.2 mg
Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks under fasted conditions, on top of insulin glargine with or without metformin.
干预措施: Insulin Glargine (Drug)
Liraglutide 1.2 mg
Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks under fasted conditions, on top of insulin glargine with or without metformin.
干预措施: Metformin (Drug)
Liraglutide 1.8 mg
Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks under fasted conditions, on top of insulin glargine with or without metformin.
干预措施: Liraglutide (Drug)
Liraglutide 1.8 mg
Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks under fasted conditions, on top of insulin glargine with or without metformin.
干预措施: Insulin Glargine (Drug)
Liraglutide 1.8 mg
Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks under fasted conditions, on top of insulin glargine with or without metformin.
干预措施: Metformin (Drug)
结局指标
主要结局
Change From Baseline to Day 56 in Plasma Glucose Corrected Area Under The Plasma Concentration-Time Curve (AUC) From Time 0.5 Hours to 4.5 Hours
时间窗: 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours post study drug administration on Day 56
Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 milligram per decilitre (mg/dL) with 1 mg/dL as limit of detection (LOD). Calculation of the AUC was made on Day -3 (baseline) and on Day 56 using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration \[time: 0.5 hours\]) to 4 hours after breakfast start (time: 4.5 hours) and corrected by subtracting pre-breakfast plasma glucose concentration (time: 0.5 hours).
次要结局
- Change From Baseline to Day 56 in Plasma Glucose Corrected AUC From Time 0.5 Hours to 5.5 Hours(0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56)
- Number of Participants With 2-Hour Post-prandial Plasma Glucose (PPG) <7.77 (mmol/L) at Day 56(Day 56)
- Change From Baseline to Day 56 in PPG Excursion(0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline); 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56)
- Change From Baseline to Day 56 in Fasting Plasma Glucose (FPG)(0.5 hour (prior to standardized breakfast) on Day -3; 0.5 hour (prior to standardized breakfast) on Day 56)
- Change From Baseline to Day 56 in Average 7-Point Self-Monitored Plasma Glucose (SMPG)(Before breakfast, 2 hours post breakfast, before lunch, 2 hours post lunch, before dinner, 2 hours post dinner, and at bedtime on Day -3 (Baseline) and on Day 56)
- Change From Baseline to Day 56 in Corrected C-Peptide AUC From Time 0.5 Hours to 5.5 Hours(0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day-3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56)
- Change From Baseline to Day 56 in Corrected Glucagon AUC From Time 0.5 Hours to 5.5 Hours(0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56)
- Change From Baseline to Day 56 in HbA1c(Pre-dose (Hour 0) on Day 1 (Baseline) and Day 56)
- Change From Baseline to Day 56 in Average Daily Insulin Glargine Dose(Day -7 (Baseline), Day 56)
- Change From Baseline to Day 55 in Gastric Emptying Half Life (t1/2)(0 (prior to standardized breakfast), 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 hours on Day -4 (baseline) and on Day 55)
- Change From Baseline to Day 55 in Gastric Emptying Coefficient(0 (7:30 clock time, prior to standardized breakfast), 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 hours on Day -4 (baseline) and on Day 55)
- Change From Baseline to Day 57/58 in 24-Hour Mean Heart Rate(Every 15 minutes from 07:00 clock time to 23:00 clock time (day-time) and every 30 minutes from 23:00 clock time to 07:00 clock time (night-time) on Day -2/-1 (Baseline) and Day 57/58)
- Change From Baseline to Day 57/58 in 24-Hour Mean Systolic Blood Pressure and Diastolic Blood Pressure(Every 15 minutes from 07:00 clock time to 23:00 clock time (day-time) and every 30 minutes from 23:00 clock time to 07:00 clock time (night-time) on Day -2/ -1 (Baseline) and Day 57/58)
- Change From Baseline to Day 57 in Body Weight(0.5 hours prior to standardized breakfast on Day -1 (Baseline); 0.5 hours prior to study drug administration on Day 57)
- Change From Baseline to Day 57 in Waist Circumference(0.5 hours prior to standardized breakfast on Day -1 (Baseline); 0.5 hours prior to IMP administration on Day 57)
- Change From Baseline to Day 56 in the Cumulative Score Mean on the Appetite Perception Using a Visual Analogue Scale After Standardized Solid Breakfast(0.5 (8:00 clock time, prior to standardized breakfast), 1.5, 2.5, 3.5, 4.5, 5.5 hours on Day -3; 0 (prior to standardized breakfast), 1.5, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56)