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Glucophage Immediate Release (GIR) China Bioequivalence Study

2019年5月3日 更新者:Merck KGaA, Darmstadt, Germany

A Randomized, Open-label, 2-Way-Crossover Study Assessing the Bioequivalence Between Single Doses of 500 mg Glucophage Immediate Release (GIR) Tablets (Sino-American Shanghai Squibb Pharmaceuticals Ltd./ Manufactured in China) and 500 mg GIR Tablets (Merck Santé s.a.s. in Semoy/ Manufactured in France) Under Fed and Fasted State in Two Groups of Healthy Subjects

The study will assess the bioequivalence between single doses of glucophage immediate release (GIR) test tablets and GIR reference tablets under fed and fasted state in healthy subjects.

研究概览

地位

完全的

条件

研究类型

介入性

注册 (实际的)

44

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

      • Beijing、中国、100053
        • Xuanwu Hospital

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 55年 (成人)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Participants had given written informed consent before any trial-related activities
  • Chinese male and female participants (at least 1/4 of each gender per trial group)
  • Aged between 18 and 55 years, inclusive
  • Weighed: 50 to 80 kilogram (kg); Body mass index (BMI): 18 to 30 kg per meter square
  • Nonsmoker since at least 3 months
  • Good physical and mental health status, determined on the basis of the medical history and a physical examination
  • All values for biochemistry and hematology tests of blood and urine within the normal range or showied no clinically relevant deviation as judged by the Investigator
  • Electrocardiogram recording (12-lead ECG) without signs of clinically relevant pathology was judged by the Investigator
  • Vital signs (blood pressure, pulse, body temperature, and respiration) in sitting position within the normal range or showing no clinically relevant deviation was judged by the Investigator
  • All women of childbearing potential (WOCBP) who were not nursing, were not pregnant, and were using highly effective methods of birth control
  • Negative screen for alcohol and drugs of abuse (cannabis, benzodiazepines, barbiturates, opiates, cocaine, and methyl amphetamine) were screened at and on admission
  • Negative screen for hepatitis A virus (HAV) antibodies, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV) antibodies, and Treponema pallidum (TP) antibodies

Exclusion Criteria:

  • Participation in a clinical trial within 90 days prior to first drug administration
  • Blood donation (equal or more than 500 milliliter [mL]) or significant blood loss within 90 days prior to first drug administration
  • Any surgical or medical condition, including findings in the medical history or in the pretrial assessments, or any other significant disease, that in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the participant in the trial or that could interfere with the trial objectives, conducted or evaluated
  • History of surgery of the gastrointestinal tract which could influence the gastrointestinal absorption and/or motility according to the Investigator's opinion
  • History or presence of relevant liver diseases or hepatic dysfunction Allergy: ascertained or presumptive hypersensitivity to the active drug substance and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considered affectted the outcome of the trial
  • Receipt of any prescription or nonprescription medication within 2 weeks before the first IMP administration, including multivitamins and herbal products (example, St John's Wort, or traditional Chinese medicines), except paracetamol
  • Renal failure or renal dysfunction (creatinine clearance < 80 mL/minute) as assessed by using the estimated measure with the Modification of Diet in Renal Disease (MDRD) equation
  • Known lack of participant compliance or inability to communicate or cooperate with the Investigator (example, language problem and poor mental status)
  • Nonacceptance of trial high-fat breakfast (example, vegetarians, vegans, and participants followed special diets)
  • Consumption of large quantities of methyl xanthine-containing beverages (> 5 cups of coffee/day or equivalent)
  • Consumption of grapefruit, cranberry or juices of these fruits, from 14 days prior to drug administration until collection of the last pharmacokinetic sample in Period 2
  • Any contraindication to Glucophage
  • Abnormal and clinically significant chest X-ray finding at screening

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:其他
  • 分配:随机化
  • 介入模型:交叉作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:First Test GIR (Fasting), Then Reference GIR (Fasting)
Participants received a single oral dose of 500 milligram (mg) of test Glucophage Immediate Release (GIR) tablet Sino-American Shanghai Squibb (SASS)/China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GIR (Merck Santé in Semoy (MSS)/France) on Day 8 in treatment period 2 under fasting condition. There was a wash-out period of 7 days between each treatment period.
Participants received 500 milligrams (mg) test GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
其他名称:
  • 二甲双胍
Participants received 500 mg reference GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
其他名称:
  • 二甲双胍
实验性的:First Reference GIR (Fasting), Then Test GIR (Fasting)
Participants received a single oral dose of 500 mg of reference GIR tablet (MSS/France) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GIR (SASS/China) on Day 8 in treatment period 2 under fasting condition. There was a wash-out period of 7 days between each treatment period.
Participants received 500 milligrams (mg) test GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
其他名称:
  • 二甲双胍
Participants received 500 mg reference GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
其他名称:
  • 二甲双胍
实验性的:First Test GIR (Fed), Then Reference GIR (Fed)
Participants received a single oral dose of 500 mg of test GIR tablet (SASS/ China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GIR (MSS/France) on Day 8 in treatment period 2 under fed condition. There was a wash-out period of 7 days between each treatment period.
Participants received 500 milligrams (mg) test GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
其他名称:
  • 二甲双胍
Participants received 500 mg reference GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
其他名称:
  • 二甲双胍
实验性的:First Reference GIR (Fed), Then Test GIR (Fed)
Participants received a single oral dose of 500 mg of reference GIR tablet (MSS/ France) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GIR (SASS/China) on Day 8 in treatment period 2 under fed condition. There was a wash-out period of 7 days between each treatment period.
Participants received 500 milligrams (mg) test GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
其他名称:
  • 二甲双胍
Participants received 500 mg reference GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
其他名称:
  • 二甲双胍

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
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Metformin (GIR Tablet Active Ingredient)
大体时间:Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Maximum Observed Plasma Concentration (Cmax) of Metformin (GIR Tablet Active Ingredient)
大体时间:Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Pharmacokinetic (PK) parameter Cmax was obtained directly from the concentration versus time curve.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

次要结果测量

结果测量
措施说明
大体时间
Time to Reach Maximum Plasma Concentration of Metformin (GIR Tablet Active Ingredient)
大体时间:Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Apparent Terminal Half-Life (t1/2) of Metformin (GIR Tablet Active Ingredient)
大体时间:Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Metformin (GIR Tablet Active Ingredient)
大体时间:Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUCextra) of Metformin (GIR Tablet Active Ingredient)
大体时间:Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
AUCextra% was defined as area under the curve from time tlast extrapolated to infinity as percentage of AUC 0-infinity. Here, tlast is the last sampling time at which the concentration is at or above the lower limit of quantification.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Elimination Rate Constant (λz) of Metformin (GIR Tablet Active Ingredient)
大体时间:Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
λz was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Total Body Clearance (CL/f) of Metformin (GIR Tablet Active Ingredient)
大体时间:Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Apparent Volume of Distribution at After Extravascular Administration (Vz/f) of Metformin (GIR Tablet Active Ingredient)
大体时间:Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Apparent Volume of Distribution at Steady-State After Extravascular Administration (Vss/f) of Metformin
大体时间:Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Vss/F was derived from concentration versus time data for all participants.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
大体时间:Baseline up to Day 15
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both Serious TEAEs and non-serious TEAEs.
Baseline up to Day 15
Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Parameters, Physical Examination Findings and 12-lead Electrocardiogram (ECG) Findings
大体时间:Baseline up to Day 15
The laboratory measurements included hematology, blood chemistry and urinalysis. Vital sign assessment included blood pressure, pulse rate and body temperature. ECG parameters included heart rate, PR, QRS,QT, RR, QTcB and QTcF Here, we are reporting number of participants with clinically significant abnormalities in Vital signs, laboratory parameters, physical findings and ECG findings.
Baseline up to Day 15

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2018年1月10日

初级完成 (实际的)

2018年1月29日

研究完成 (实际的)

2018年1月29日

研究注册日期

首次提交

2017年12月22日

首先提交符合 QC 标准的

2018年1月5日

首次发布 (实际的)

2018年1月8日

研究记录更新

最后更新发布 (实际的)

2019年7月15日

上次提交的符合 QC 标准的更新

2019年5月3日

最后验证

2019年4月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • MS200084_0009

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

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