A Randomized, Open-label, Two-way Crossover Study Assessing the Bioequivalence (BE) Between Single Dose of 750 mg Glucophage® XR Tablets (PT Merck Tbk, Jakarta, Indonesia-Manufactured) and 750 mg Glucophage® XR Tablets (Merck Santé, Semoy, France-Manufactured) Under Fasted State in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of Metformin
研究概览
简要总结
The purpose of this study is to assess bioequivalence between metformin hydrochloride (Glucophage® XR) manufactured in PT Merck Tbk, Indonesia (test drug) and metformin hydrochloride (Glucophage® XR) manufactured in Merck Santé, France (comparator drug) following single oral dose administration under fasting condition.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants has provided written informed consent prior to the conduct of any study-related activities
- •Body mass index of 18 to 25 kilogram per square meter (kg/m^2)
- •Good physical and mental health status, determined on the basis of medical history and physical examination
- •Vital signs (blood pressure, pulse rate, respiratory rate and body temperature) in sitting position within the normal range or showing no clinically relevant deviation per the Investigator's opinion
- •All values for laboratory assessments (hematology, clinical chemistry and urinalysis) within the normal range or showing no clinically relevant deviation per the Investigator's opinion
- •No clinically significant abnormality on 12-lead electrocardiogram (ECG) recording as judged by the Investigator; corrected QT interval (QTc) (Bazett) should be less than equals to (<=) 450 milliseconds (ms)
- •Non-smoker or smoker less than 10 cigarettes per day
- •Women of childbearing potential (WOCBP) who are not nursing, are not pregnant, and are using highly effective methods of birth control. Female participants may also be enrolled if they are postmenopausal or surgically sterilized/ hysterectomized at least 6 months prior to study participation
- •WOCBP must have a negative urine pregnancy test at Screening and on each admission (Day 1 of each dosing period)
- •Negative screen for alcohol and drugs abuse (opiate class, barbiturates, cocaine and metabolites, amphetamines, cannabinoids and benzodiazepines) at Screening and on each Study Check-In (Day -1 of each dosing period)
- •Negative screen for Hepatitis B surface antigen (HBsAg), Hepatitis C Virus (HCV) antibodies and/or Human Immunodeficiency Virus (HIV) antibodies.
排除标准
- •Participation in a clinical trial/study within 90 days prior to Screening
- •Blood donation (equal or more than 300 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 prestudy 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 study or that could interfere with the study objectives, conduct or evaluation
- •History of malignant diseases, except in-situ basal cell skin tumors treated with curative intent
- •History of surgery of the gastrointestinal tract which could influence the gastrointestinal absorption and/or motility per the Investigator's opinion
- •History or presence of relevant liver diseases or hepatic dysfunction (laboratory result for liver function test greater than equals to (>=) 1.5 upper limit of normal (ULN)
- •History or presence of renal failure or renal dysfunction based on clinical symptoms and finding (serum creatinine concentration >1.4 milligram per milliliter (mg/mL)
- •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 considers may affect the outcome of the study
- •Receipt of any prescription or non-prescription medication within 14 days before the first drug administration, except for hormonal contraceptives in female, and including multivitamins and herbal products (e.g. St John's Wort)
- •Consumption of large quantities of methylxanthine-containing beverages (> 5 cups of coffee/day or equivalent)
- •Consumption of grapefruit, orange, cranberry or juices of these three fruits, 24 hours prior to drug administration
- •Known lack of participant compliance or inability to communicate or cooperate with the Investigator (e.g., language problem, poor mental status)
研究组 & 干预措施
First Glucophage XR (Test), Then Glucophage XR (Comparator)
Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 2 under fasting conditions. The two periods were separated by a 7-day wash-out period.
干预措施: Glucophage XR (Test drug) (Drug)
First Glucophage XR (Test), Then Glucophage XR (Comparator)
Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 2 under fasting conditions. The two periods were separated by a 7-day wash-out period.
干预措施: Glucophage XR (Comparator drug) (Drug)
First Glucophage XR (Comparator), Then Glucophage XR (Test)
Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 2 under fasting conditions. The two periods were separated by a 7-day wash-out period.
干预措施: Glucophage XR (Test drug) (Drug)
First Glucophage XR (Comparator), Then Glucophage XR (Test)
Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 2 under fasting conditions. The two periods were separated by a 7-day wash-out period.
干预措施: Glucophage XR (Comparator drug) (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of Metformin
时间窗: Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
The maximum plasma concentration of Metformin.
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin
时间窗: Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration.
次要结局
- Area Under Plasma Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin(Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin(Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1)
- Terminal Elimination Half-life in Plasma (t½) of Metformin(Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs(Up to Day 51)