A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763 Following Single and Multiple Ascending Doses in Healthy Subjects and Patients With Type 2 Diabetes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- Number of Patients with adverse events, serious adverse events and death
研究概览
简要总结
This study is a three part study to assess the safety and efficacy of LEZ763 on normal healthy volunteers and patients with Type 2 Diabetes.
研究设计
- 研究类型
- Interventional
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
LEZ763
Part I- Healthy volunteers enrolled into 6 single-ascending dose cohorts Part II- Healthy volunteers enrolled into 5 multiple-ascending dose cohorts. Part III- LEZ763 will be given orally once daily for 28 days in a randomized and blinded manner
干预措施: LEZ763 (Drug)
Placebo
Part I : Healthy volunteers enrolled in 6 single ascending dose cohorts to receive matching placebo of LEZ763. Part II: Healthy volunteers enrolled in 5 multiple ascending dose cohorts to receive matching placebo of LEZ763. Part III- Placebo will be given orally once daily for 28 days to patients assigned to placebo in a randomized and blinded manner
干预措施: Placebo (Drug)
Sitagliptin
Sitaglitpin will be given orally once daily for 28 days to patients assigned to this treatment in a randomized and blinded manner
干预措施: Sitagliptin (Drug)
结局指标
主要结局
Number of Patients with adverse events, serious adverse events and death
时间窗: Day 28
An adverse event is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. Adverse events will also be determined on the basis of clinical laboratory assessments, electrocardiographic evaluations and vital signs determinations.
Pharmacokinetics of LEZ763 (Part I): area under the plasma concentration-time curve from time zero to infinity (AUCinf)
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1; 24 and 36 hours Day 2; Day 3, Day 4
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single dose
Pharmacokinetics of LEZ763 (Part I): area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1; 24 and 36 hours Day 2; Day 3, Day 4
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single dose
Pharmacokinetics of LEZ763 (Part I): Terminal elimination half-life (T1/2)
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1; 24 and 36 hours Day 2; Day 3, Day 4
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single dose
Pharmacokinetics of LEZ763 (Part I): Apparent systemic (or total body) clearance from plasma following extravascular administration (CL/F)
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1; 24 and 36 hours Day 2; Day 3, Day 4
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single dose
Pharmacokinetics of LEZ763 (Part I) : Observed maximum plasma concentration (Cmax) following drug administration
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1; 24 and 36 hours Day 2; Day 3, Day 4
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single and multiple doses
Pharmacokinetics of LEZ763 (Part I): time to reach the maximum concentration after drug administration (Tmax)
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1; 24 and 36 hours Day 2; Day 3, Day 4
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single dose
Pharmacokinetics of LEZ763 (Part II) : Observed maximum plasma concentration (Cmax) following drug administration
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 10
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses
Pharmacokinetics of LEZ763 (Part II): time to reach the maximum concentration after drug administration (Tmax)
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 10
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses
Pharmacokinetics of LEZ763 (Part II): Accumulation ratio(Racc)
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 27
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses
Pharmacokinetics of LEZ763 (Part III) : Observed maximum plasma concentration (Cmax) following drug administration
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 27
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses
Pharmacokinetics of LEZ763 (Part III): time to reach the maximum concentration after drug administration (Tmax)
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 27
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses
Pharmacokinetics of LEZ763 (Part III): Area under the plasma concentration-time curve from time zero to the end of the dosing interval tau (AUCtau)
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 27
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single and multiple doses
Pharmacokinetics of LEZ763 (Part III): Accumulation ratio(Racc)
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 27
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single and multiple doses
Pharmacokinetics of LEZ763 and Sitagliptin (Part III): Observed maximum plasma concentration (Cmax) following drug administration
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 and 4 hours post-dose on Day 28
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses
Pharmacokinetics of LEZ763 and Sitagliptin (Part III): Area under the plasma concentration-time curve from time zero to the end of the dosing interval tau (AUCtau)
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 and 4 hours post-dose on Day 28
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses
Pharmacokinetics of LEZ763 and Sitagliptin (Part III): Time to reach the maximum concentration after drug administration (Tmax)
时间窗: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 and 4 hours post-dose on Day 28
Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses
Area under the effect curve (AUC0-4h) over the 4-hour post-dose period to measure glucose response following a standard mixed meal test
时间窗: 4 hour post-dose Day 27
次要结局
- Area under the serum Glucagon-like-peptide 1 (GLP-1) curve (AUC0-24 hours)(Pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 and 4 hours post-dose on Day -1, Day 1, Day 27, and Day 28)
- 2-hour value of post-prandial glucose(Day 1 of Part I, Day 1 and day 10 of Part II)
- Change from baseline in Fasting C-peptide at Day 27 (Part III)(Baseline, Day 27)
- Change from baseline in Fasting Insulin at Day 27 (Part III)(Baseline , Day 27)
- Change from baseline in fasting plasma glucose at Day 27 (Part III)(Baseline , Day 27)
- Change From Baseline in peak glucose level following meal Test at Day 27 (Part III)(Baseline , Day 27)
- Peak effect (Emax) on postprandial GLP-1 (Part III)(Baseline , Day 27)
- Change from baseline in Peptide YY (PYY) (Part III)(Baseline , Day 27)
- Change from baseine in Gastric inhibit polypeptide (GIP) (Part III)(Baseline , Day 27)