GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Metformin (GETGOAL-F1)
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, 24-week Study Followed by an Extension Assessing the Efficacy and Safety of AVE0010 in Two Titration Regimens on Top of Metformin in Patients With Type 2 Diabetes Not Adequately Controlled With Metformin
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, over a period of 24 weeks of treatment, followed by an extension.
The primary objective is to assess the effects of lixisenatide when added to metformin on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction when it is used in two steps dose titration regimen at Week 24.
Secondary objectives are to assess the effects of lixisenatide when added to metformin on glycemic control in comparison to placebo in terms of HbA1c reduction when it is used in a one-step dose titration regimen, the percentage of patients with HbA1c less than 7 percent or less than or equal to 6.5%, body weight, fasting plasma glucose (FPG); to assess the safety, tolerability, pharmacokinetics (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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Kiev、乌克兰
- Sanofi-Aventis Administrative Office
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Santafe de Bogota、哥伦比亚
- Sanofi-Aventis Administrative Office
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Mexico、墨西哥
- Sanofi-Aventis Administrative Office
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Sao Paulo、巴西
- Sanofi-Aventis Administrative Office
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Berlin、德国
- Sanofi-Aventis Administrative Office
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Milano、意大利
- Sanofi-Aventis Administrative Office
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Brastislava、斯洛伐克
- Sanofi-Aventis Administrative Office
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Santiago、智利
- Sanofi-Aventis Administrative Office
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Warszawa、波兰
- Sanofi-Aventis Administrative Office
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Tallinn、爱沙尼亚
- Sanofi-Aventis Administrative Office
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Vilnius、立陶宛
- Sanofi-Aventis Administrative Office
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Bucuresti、罗马尼亚
- Sanofi-Aventis Administrative Office
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New Jersey
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Bridgewater、New Jersey、美国、08807
- Sanofi-Aventis Administrative Office
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Makati City、菲律宾
- Sanofi-Aventis Administrative Office
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Kuala Lumpur、马来西亚
- Sanofi-Aventis Administrative Office
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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 at the time of screening visit, insufficiently controlled with metformin at a stable dose of at least 1.5 gram/day for at least 3 months prior to screening visit
Exclusion Criteria:
- HbA1c less than (<) 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 an antidiabetic pharmacological agent other than metformin within the 3 months preceding the screening
- FPG at screening >250 milligram per deciliter (mg/dL) (>13.9 millimole per liter [mmol/L])
- Body mass index less than or equal to (<)20 kilogram per square meter (kg/m^2)
- Weight change of more than 5 kg during the 3 months preceding the screening visit
- History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease
- 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 supine systolic or diastolic blood pressure >180 millimeter of mercury (mmHg) or >95 mmHg, respectively
- Laboratory findings at the time of screening: aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP): >2 times upper limit of the normal (ULN) laboratory range; amylase and/or lipase: >3 times ULN; total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome); hemoglobin <11 gram/deciliter and/or neutrophils <1500 per cubic millimeter (mm^3) and/or platelets <100000/mm^3; positive test for Hepatitis B surface antigen (HBsAg) and/or Hepatitis C antibody (HCAb) and positive serum pregnancy test in females of childbearing potential
- Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram (ECG) 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 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 (for example, sulfonylurea, alpha glucosidase inhibitor, thiazolidinedione, rimonabant, exenatide, dipeptidylpeptidase-4 (DPP-IV) inhibitor, insulin) within 3 months prior to the time of screening
- Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 3 months prior to the time of screening
- Use of any investigational drug within 3 months prior to study
- Any previous treatment with lixisenatide or participation in any 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 and gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening
- Allergic reaction to any glucagon like peptide-1 (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 (Two-Step Titration)
2-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment.
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其他名称:
每天早餐前一小时内通过皮下注射自行给药一次。
二甲双胍继续以稳定剂量(每天至少 1.5 克)直至治疗结束。
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实验性的:Lixisenatide (One-Step Titration)
1-step initiation regimen of lixisenatide: 10 mcg QD for 2 weeks, then 20 mcg QD up to the end of treatment.
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其他名称:
每天早餐前一小时内通过皮下注射自行给药一次。
二甲双胍继续以稳定剂量(每天至少 1.5 克)直至治疗结束。
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安慰剂比较:Placebo (Two-Step Titration)
2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment.
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其他名称:
每天早餐前一小时内通过皮下注射自行给药一次。
二甲双胍继续以稳定剂量(每天至少 1.5 克)直至治疗结束。
|
安慰剂比较:Placebo (One-Step Titration)
1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, then 20 mcg QD up to the end of treatment.
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其他名称:
每天早餐前一小时内通过皮下注射自行给药一次。
二甲双胍继续以稳定剂量(每天至少 1.5 克)直至治疗结束。
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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 time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required. The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol |
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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第 24 周空腹血糖 (FPG) 相对于基线的变化
大体时间:基线,第 24 周
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通过从第 24 周的值中减去基线值来计算变化。
该疗效变量的治疗期间是从第一次研究药物给药到最后一次研究药物给药后 1 天的时间,即第 12 次就诊(第 24 周)或第 169 天(如果第 12 次就诊不可用)或之前,在引入抢救疗法之前。
对于要包括在 mITT 人群中的患者,需要对至少 1 个功效变量进行基线和至少 1 次基线后评估。
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基线,第 24 周
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第 24 周时体重相对于基线的变化
大体时间:基线,第 24 周
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通过从第 24 周的值中减去基线值来计算变化。
该疗效变量的治疗期间是从第一次研究药物给药到最后一次研究药物给药后 3 天的时间,在第 12 次就诊(第 24 周)或第 169 天(如果第 12 次就诊不可用)或之前,在引入抢救疗法之前。
对于要包括在 mITT 人群中的患者,需要对至少 1 个功效变量进行基线和至少 1 次基线后评估。
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基线,第 24 周
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第 24 周糖化血红蛋白 (HbA1c) 水平低于 7% 的患者百分比
大体时间:第 24 周
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该疗效变量的治疗期间是从第一次研究药物给药到最后一次研究药物给药后 3 天的时间,在第 12 次就诊(第 24 周)或第 169 天(如果第 12 次就诊不可用)或之前,在引入抢救疗法之前。
对于要包括在 mITT 人群中的患者,需要对至少 1 个功效变量进行基线和至少 1 次基线后评估。
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第 24 周
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第 24 周糖化血红蛋白 (HbA1c) 水平低于或等于 6.5% 的患者百分比
大体时间:第 24 周
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该疗效变量的治疗期间是从第一次研究药物给药到最后一次研究药物给药后 3 天的时间,在第 12 次就诊(第 24 周)或第 169 天(如果第 12 次就诊不可用)或之前,在引入抢救疗法之前。
对于要包括在 mITT 人群中的患者,需要对至少 1 个功效变量进行基线和至少 1 次基线后评估。
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第 24 周
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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-measured 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 >270 milligram/deciliter (mg/dL) (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG >240 mg/dL (13.3 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 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 |
---|---|---|
第 24 周体重较基线至少减轻 5% 的患者百分比
大体时间:基线,第 24 周
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该疗效变量的治疗期间是从第一次研究药物给药到最后一次研究药物给药后 3 天的时间,在第 12 次就诊(第 24 周)或第 169 天(如果第 12 次就诊不可用)或之前,在引入抢救疗法之前。
对于要包括在 mITT 人群中的患者,需要对至少 1 个功效变量进行基线和至少 1 次基线后评估。
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基线,第 24 周
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Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia
大体时间:First dose of study drug up to 3 days after the last dose administration, for up to 112 weeks
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Symptomatic hypoglycemia was an event with clinical symptoms that were considered to result from a hypoglycemic episode with an accompanying plasma glucose less than 60 mg/dL (3.3 mmol/L) or associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration if no plasma glucose measurement was available.
Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the patient required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available.
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First dose of study drug up to 3 days after the last dose administration, for up to 112 weeks
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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
- Bolli GB, Munteanu M, Dotsenko S, Niemoeller E, Boka G, Wu Y, Hanefeld M. Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin (GetGoal-F1). Diabet Med. 2014 Feb;31(2):176-84. doi: 10.1111/dme.12328. Epub 2013 Oct 24.
- Ambery P, Donner TW, Biswas N, Donaldson J, Parkin J, Dayan CM. Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study. Diabet Med. 2014 Apr;31(4):399-402. doi: 10.1111/dme.12361. Epub 2013 Dec 6.
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
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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Shenzhen Second People's Hospital未知
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Autolus Limited邀请报名
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Technische Universität Dresden未知
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Lisata Therapeutics, Inc.完全的
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Centre Hospitalier Universitaire de Saint EtienneAssociation Lyonnaise de Logistique Posthospitalière终止