A Phase I, Randomized, Double-blind, Placebo- and Active-controlled, Single- and Multiple-ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of DWP16001 Following Oral Administration in Healthy Male Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 123
- 试验地点
- 1
- 主要终点
- Number of Participants With Clinically Significant Vital Sign findings
研究概览
简要总结
This is a dose block-randomized, double-blind, placebo- and active-controlled, single and multiple dosing, dose-escalation clinical phase 1 trial to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of DWP16001 after oral administration in healthy male volunteers.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 19 Years 至 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male adults aged 19 to 50 at the time of screening test.
- •Body weight between 50.0 kg and 90.0 kg and Body Mass Index (BMI) between 18.0 and 27.
- •Written consent on voluntary decision of participation prior to the screening procedure after being fully informed of and completely understanding this study.
- •Eligible to participate in the study by discretion of the investigator following medical examination by interview, physical examination, and clinical examination.
排除标准
- •Presence of a clinically significant hepatic, renal, nervous, respiratory, endocrine, blood•tumor, cardiovascular, urogenital, psychiatric disorder or prior history.
- •Presence or prior history of a gastrointestinal disorder (e.g., gastrointestinal ulcers, gastritis, stomach cramps, gastroesophageal reflux disease, Crohn's disease, etc.), or prior history of surgery (except for simple appendectomy or hernia surgery) that may affect safety and PK/PD assessment.
- •Hypersensitivity to a drug containing an ingredient of the investigational product (DWP16001), Dapagliflozin or similar ingredient or other drugs (e.g., aspirin, antibiotics, etc.) or medical history of clinically significant hypersensitivity.
- •Following laboratory abnormalities identified during the screening test:
- •AST (SGOT), ALT (SGPT) >1.5 upper limit of normal range
- •Creatinine clearance calculated by the MDRD equation < 90 mL/min
- •Repeatedly confirmed QTc interval > 450 ms
- •Fasting serum glucose > 110mg/dL or < 70mg/dL
- •Serum HbA1c > 6.5 mg/dL
研究组 & 干预措施
Cohort 1: DWP16001 Amg
DWP16001 Amg, tablets, orally, single dose administration
干预措施: Dapagliflozin (Drug)
Cohort 1: DWP16001 Amg
DWP16001 Amg, tablets, orally, single dose administration
干预措施: Placebo (Drug)
Cohort 1: DWP16001 Amg
DWP16001 Amg, tablets, orally, single dose administration
干预措施: DWP16001 (Drug)
Cohort 2: DWP16001 Bmg
DWP16001 Bmg, tablets, orally, single dose administration
干预措施: DWP16001 (Drug)
Cohort 2: DWP16001 Bmg
DWP16001 Bmg, tablets, orally, single dose administration
干预措施: Placebo (Drug)
Cohort 2: DWP16001 Bmg
DWP16001 Bmg, tablets, orally, single dose administration
干预措施: Dapagliflozin (Drug)
Cohort 3: DWP16001 Cmg
DWP16001 Cmg, tablets, orally, single dose administration
干预措施: DWP16001 (Drug)
Cohort 3: DWP16001 Cmg
DWP16001 Cmg, tablets, orally, single dose administration
干预措施: Placebo (Drug)
Cohort 3: DWP16001 Cmg
DWP16001 Cmg, tablets, orally, single dose administration
干预措施: Dapagliflozin (Drug)
Cohort 4: DWP16001 Dmg
DWP16001 Dmg, tablets, orally, single dose administration
干预措施: DWP16001 (Drug)
Cohort 4: DWP16001 Dmg
DWP16001 Dmg, tablets, orally, single dose administration
干预措施: Placebo (Drug)
Cohort 4: DWP16001 Dmg
DWP16001 Dmg, tablets, orally, single dose administration
干预措施: Dapagliflozin (Drug)
Cohort 5: DWP16001 Emg
DWP16001 Emg, tablets, orally, single dose administration
干预措施: DWP16001 (Drug)
Cohort 5: DWP16001 Emg
DWP16001 Emg, tablets, orally, single dose administration
干预措施: Placebo (Drug)
Cohort 5: DWP16001 Emg
DWP16001 Emg, tablets, orally, single dose administration
干预措施: Dapagliflozin (Drug)
Cohort 6: DWP16001 Fmg
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: DWP16001 (Drug)
Cohort 6: DWP16001 Fmg
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: Placebo (Drug)
Cohort 6: DWP16001 Fmg
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: Dapagliflozin (Drug)
Cohort 7: DWP16001 Gmg
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: DWP16001 (Drug)
Cohort 7: DWP16001 Gmg
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: Placebo (Drug)
Cohort 7: DWP16001 Gmg
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: Dapagliflozin (Drug)
Cohort 8: DWP16001 Hmg
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: DWP16001 (Drug)
Cohort 8: DWP16001 Hmg
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: Placebo (Drug)
Cohort 8: DWP16001 Hmg
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: Dapagliflozin (Drug)
Cohort 9: DWP16001 Img
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: DWP16001 (Drug)
Cohort 9: DWP16001 Img
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: Placebo (Drug)
Cohort 9: DWP16001 Img
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: Dapagliflozin (Drug)
Cohort 10: DWP16001 Jmg
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: DWP16001 (Drug)
Cohort 10: DWP16001 Jmg
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: Placebo (Drug)
Cohort 10: DWP16001 Jmg
DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
干预措施: Dapagliflozin (Drug)
结局指标
主要结局
Number of Participants With Clinically Significant Vital Sign findings
时间窗: Day -2(Randomization) to Day 8~12(Post-study visit) in single ascending dose or Day-3d to Day 22~ (Post-study visit)
Blood pressure, pulse and body temperature were tested. The Average, Median, Standard Deviation, Min, Max values will be calculated to assess the safety/tolerability
Number of Participants With Clinically Significant Laboratory results
时间窗: Day -2(Randomization) to Day 8~12(Post-study visit) in single ascending dose or Day-3d to Day 22~ (Post-study visit)
Hematology, Blood chemistry, Coagulation and Urinalysis were tested. The Average, Median, Standard Deviation, Min, Max values will be calculated to assess the safety/tolerability.
Number and percentage of Participants With Adverse Events (AE)
时间窗: Day -2(Randomization) to Day 8~12(Post-study visit) in single ascending dose or Day-3d to Day 22~ (Post-study visit)
All AE standardized using MedDRA was assessed by investigator using the protocol defined grading system. Intensity was categorized as mild, moderate and severe
Number and percentage of Participants With Adverse Drug Reactions (ADR)
时间窗: Day -2(Randomization) to Day 8~12(Post-study visit) in single ascending dose or Day-3d to Day 22~ (Post-study visit)
An adverse drug reaction (ADR) is an injury caused by taking an investigational product
Number of Participants With Clinically Significant Electrocardiogram(12-lead ECG) findings
时间窗: Day -2(Randomization) to Day 8~12(Post-study visit) in single ascending dose or Day-3d to Day 22~ (Post-study visit)
Ventricular rate, RR interval, PR interval, QRS duration, QTcB and QTcF were recorded. The results of 12-lead ECG will be categorized Normal/Abnormal NCS(No clinically significant)/Abnormal CS(clinically significant).
次要结局
- Cmax: Maximum concentration of DWP16001(0 hour (pre-dose), 0.25 hour, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12hour, 24 hour, 36 hour, 48 hour, 72 hour)
- Cmax,ss: Maximum concentration of DWP16001 at steady state(Day1 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour, Day 4, 7, 10, 13 0 hour (pre dose), Day 15 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour)
- Cmin,ss: Minimum concentration of DWP16001 at steady state(Day1 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour, Day 4, 7, 10, 13 0 hour (pre dose), Day 15 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour)
- Time of maximum concentration(0 hour (pre-dose), 0.25 hour, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12hour, 24 hour, 36 hour, 48 hour, 72 hour)
- Tmax,ss: Time of maximum concentration at steady state(Day1 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour, Day 4, 7, 10, 13 0 hour (pre dose), Day 15 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour)
- AUClast: Area under the plasma concentration-time curve from time 0 to 72hours(0 hour (pre-dose), 0.25 hour, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12hour, 24 hour, 36 hour, 48 hour, 72 hour)
- AUCinf: Area under the plasma concentration-time curve from time 0 to infinity(0 hour (pre-dose), 0.25 hour, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12hour, 24 hour, 36 hour, 48 hour, 72 hour)
- AUCtau: Area under the plasma concentration-time curve from time 0 to tau(dosing interval)(Day1 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour, Day 4, 7, 10, 13 0 hour (pre dose), Day 15 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour)
- T1/2: Elimination half-life(Day1 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour, Day 4, 7, 10, 13 0 hour (pre dose), Day 15 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour)
- concentration of serum glucose(Day 1 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour, Day 4, 7, 10, 13 pre dose, Day 15 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour)
- concentration of insulin(Day -1 pre dose, 0.5, 1, 1.5, 2, 3, 4 hour, Day 15 pre dose, 0.5, 1, 1.5, 2, 3, 4 hour)
- Changes from baseline for Body weight in kilograms(Day -1 0 hour, Day 15 0 hour)
- Changes from baseline for HbA1C in percent(Day -1 0 hour, Day 15 0 hour)
- concentration of Urine glucose excretion(Day 1 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour, Day 4, 7, 10, 13 pre dose, Day 15 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour)