Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin (GetGoal-M-Asia)
Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin (With or Without Sulfonylurea): a Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study With 24-week Treatment Period
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.
研究概览
详细说明
研究类型
注册 (实际的)
阶段
- 第三阶段
联系人和位置
学习地点
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Beijing、中国、100034
- Investigational Site Number 156011
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Beijing、中国、100101
- Investigational Site Number 156012
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Beijing、中国、100191
- Investigational Site Number 156019
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Beijing、中国、100700
- Investigational Site Number 156002
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Beijing、中国、100730
- Investigational Site Number 156003
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Beijing、中国、100730
- Investigational Site Number 156009
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Beijing、中国、100853
- Investigational Site Number 156001
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Changchun、中国、130041
- Investigational Site Number 156036
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Changsha、中国、410008
- Investigational Site Number 156016
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Changsha、中国、410011
- Investigational Site Number 156015
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Chengdu、中国、610041
- Investigational Site Number 156006
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Chengdu、中国、610072
- Investigational Site Number 156032
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Dalian、中国、116027
- Investigational Site Number 156010
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Guangzhou、中国、510080
- Investigational Site Number 156004
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Guangzhou、中国、510080
- Investigational Site Number 156008
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Guangzhou、中国、510630
- Investigational Site Number 156025
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Haikou、中国、57028
- Investigational Site Number 156031
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Harbin、中国、150001
- Investigational Site Number 156014
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Hefei、中国、230022
- Investigational Site Number 156029
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Qingdao、中国、266003
- Investigational Site Number 156013
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Shanghai、中国、200003
- Investigational Site Number 156007
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Shanghai、中国、200065
- Investigational Site Number 156030
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Shenyang、中国、110004
- Investigational Site Number 156020
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Suzhou、中国、215004
- Investigational Site Number 156035
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Taiyuan、中国、030001
- Investigational Site Number 156033
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Tianjin、中国、300052
- Investigational Site Number 156037
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Xi'An、中国、710032
- Investigational Site Number 156022
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Xi'An、中国、710061
- Investigational Site Number 156023
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Bangkok、泰国、10400
- Investigational Site Number 764002
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Hong Kong、香港
- Investigational Site Number 344001
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Hong Kong、香港
- Investigational Site Number 344003
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Shatin, Nt、香港
- Investigational Site Number 344002
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Kelantan、马来西亚、16150
- Investigational Site Number 458001
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Kuala Lumpur、马来西亚、59100
- Investigational Site Number 458003
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Putrajaya、马来西亚、62250
- Investigational Site Number 458002
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion criteria:
- Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with metformin alone or metformin with sulfonylurea at the time of the screening visit
Exclusion criteria:
- HbA1c <7% or greater than (>) 10% at screening
- At the time of screening age < legal age of majority
- Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method
- Type 1 diabetes mellitus
- Treatment with metformin not at a stable dose of at least 1.0 gram per day or more than 1.5 gram per day for at least 3 months prior to screening visit
- In case of treatment with sulfonylurea, if the sulfonylurea dosage is less than the maximum effective dose (that is, half of the maximum recommended dose according to local labeling), or is not at a stable (unchanged) dose for at least 3 months prior to screening
- FPG at screening >250 milligram per deciliter (mg/dL) (>13.9 millimole per liter [mmol/L])
- History of hypoglycemia unawareness
- Body mass index <=20 kilogram per square meter (kg/m^2)
- Weight change of >5 kg during the 3 months preceding the screening visit
- History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, or inflammatory bowel disease or patients considered by the investigator at high risk for acute pancreatitis (for example, with known history of biliary gallstone[s], or with very high triglyceride level [>=5.65 mmol/L]) at the time of screening
- Personal or family history of medullary thyroid cancer or genetic conditions that predispose to medullary thyroid cancer (for example, multiple endocrine neoplasia syndromes);
- History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
- Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within 3 months prior to the time of screening
- Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization
- Known history of drug or alcohol abuse within 6 months prior to the time of screening
- Cardiovascular, hepatic, neurological, endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period
- Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic blood pressure (SBP) or diastolic blood pressure (DBP) >180 millimeter of mercury (mmHg) or >95 mmHg, respectively
- Laboratory findings at the time of screening: amylase and/or lipase: >3 times upper limit of normal (ULN); hemoglobin <11 gram/deciliter and/or neutrophils <1500 per cubic millimeter (mm^3) and/or platelets <100 000/mm^3; calcitonin >20 picogram per milliliter (5.9 picomole per liter) ; and positive test for Hepatitis B surface antigen and/or Hepatitis C antibody
- Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram, or vital signs at the time of screening that, in the judgment of the investigator or any sub-investigator, precludes safe completion of the study or constrains efficacy assessment
- Patients who are considered by the investigator or any sub-investigator as inappropriate for this study for any reason (for example, impossibility to meet specific protocol requirements, such as attending scheduled visits, being able to do self-injections; likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol; investigator or any sub-investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol)
- Use of oral or injectable antidiabetic or hypoglycemic agents other than metformin and sulfonylurea (for example, alpha-glucosidase inhibitor, thiazolidinedione, glucagon-like peptide -1 [GLP-1], receptor agonist, dipeptidyl-peptidase-4 inhibitors, insulin) within 3 months prior to the time of screening
- Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to the time of screening
- Use of any investigational drug within 3 months prior to screening;
- Participation in a previous study with lixisenatide
- Renal impairment defined with creatinine >1.4 mg/dL in women and creatinine >1.5 mg/dL in men
- Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to gastroparesis, unstable (that is, worsening) and not controlled (that is, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening
- Allergic reaction to any GLP-1 agonist in the past (for example, exenatide, liraglutide) or to metacresol
- Additional exclusion criteria at the end of the run-in phase: informed consent withdrawal; lack of compliance during the single-blind placebo run-in phase (>2 injections missed); and patient with any adverse event which precludes the inclusion in the study, as assessed by the investigator
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Lixisenatide
1-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 2 weeks, followed by 20 mcg QD up to Week 24.
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每天早餐前一小时内通过皮下注射自我给药一次。
其他名称:
Metformin to be continued at stable dose (at least 1.0 gram per day and not more than 1.5 gram per day) up to Week 24.
Sulfonylurea if given at screening, to be continued up to Week 24.
In patients with a screening HbA1c <8% the dose is decreased by 25% to 50% at randomization and then increased up to the screening dose between Week 4 and 12 as per fasting self-monitored plasma glucose (SMPG) values.
In patients with a screening HbA1c >=8%, the dose is not to be changed at randomization.
In any case, after Week 12, sulfonylurea is to be continued at a stable dose.
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安慰剂比较:Placebo
1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, followed by 20 mcg QD up to Week 24.
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其他名称:
Metformin to be continued at stable dose (at least 1.0 gram per day and not more than 1.5 gram per day) up to Week 24.
Sulfonylurea if given at screening, to be continued up to Week 24.
In patients with a screening HbA1c <8% the dose is decreased by 25% to 50% at randomization and then increased up to the screening dose between Week 4 and 12 as per fasting self-monitored plasma glucose (SMPG) values.
In patients with a screening HbA1c >=8%, the dose is not to be changed at randomization.
In any case, after Week 12, sulfonylurea is to be continued at a stable dose.
每天早餐前一小时内通过皮下注射自我给药一次。
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
大体时间:Baseline, Week 24
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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.
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Baseline, Week 24
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
大体时间:Baseline, Week 24
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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.
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Baseline, Week 24
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Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24
大体时间:Baseline, Week 24
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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.
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Baseline, Week 24
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Change From Baseline in Body Weight at Week 24
大体时间:Baseline, Week 24
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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.
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Baseline, Week 24
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Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24
大体时间:Week 24
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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.
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Week 24
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Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24
大体时间:Week 24
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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.
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Week 24
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Change From Baseline in Glucose Excursion at Week 24
大体时间:Baseline, Week 24
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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.
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Baseline, Week 24
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Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period
大体时间:Baseline up to Week 24
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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.
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Baseline up to Week 24
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
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Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24
大体时间:Baseline, Week 24
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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.
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Baseline, Week 24
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有症状性低血糖和严重症状性低血糖的患者人数
大体时间:在最后一次给药后 3 天内首次服用研究药物
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症状性低血糖是一种具有临床症状的事件,被认为是由伴随血浆葡萄糖低于 60 mg/dL (3.3 mmol/L) 的低血糖发作引起的,或者与口服碳水化合物、静脉注射葡萄糖或胰高血糖素后迅速恢复有关,如果没有可用的血浆葡萄糖测量值。
严重症状性低血糖是症状性低血糖事件,其中患者需要他人的帮助,并且与血浆葡萄糖水平低于 36 mg/dL (2.0 mmol/L) 或口服碳水化合物、静脉注射葡萄糖或胰高血糖素后迅速恢复有关, 如果没有血浆葡萄糖测量可用。
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在最后一次给药后 3 天内首次服用研究药物
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合作者和调查者
赞助
出版物和有用的链接
一般刊物
- Yu Pan C, Han P, Liu X, Yan S, Feng P, Zhou Z, Lv X, Tian H, Jin Kui Y, Su B, Shang S, Niemoeller E. Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (GetGoal-M-Asia). Diabetes Metab Res Rev. 2014 Nov;30(8):726-35. doi: 10.1002/dmrr.2541.
- Seino H, Onishi Y, Naito Y, Komatsu M. Lixisenatide improves glycemic outcomes of Japanese patients with type 2 diabetes: a meta-analysis. Diabetol Metab Syndr. 2016 Jun 1;8:36. doi: 10.1186/s13098-016-0151-7. eCollection 2016.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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利西拉来 (AVE0010)的临床试验
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Sanofi完全的急性冠状动脉综合征比利时, 中国, 日本, 丹麦, 美国, 白俄罗斯, 墨西哥, 菲律宾, 以色列, 奥地利, 塞尔维亚, 爱沙尼亚, 立陶宛, 智利, 哥伦比亚, 德国, 拉脱维亚, 秘鲁, 乌克兰, 埃及, 意大利, 法国, 巴西, 印度, 危地马拉, 南非, 台湾, 加拿大, 保加利亚, 葡萄牙, 阿根廷, 澳大利亚, 厄瓜多尔, 芬兰, 乔治亚州, 大韩民国, 荷兰, 挪威, 巴拿马, 波兰, 罗马尼亚, 俄罗斯联邦, 西班牙, 瑞典, 瑞士, 突尼斯, 火鸡, 阿拉伯联合酋长国, 英国