AN OPEN LABEL, BALANCED, RANDOMIZED, TWO-TREATMENT, TWO-PERIOD, TWO-SEQUENCE, CROSSOVER, SINGLE ORAL DOSE, BIOEQUIVALENCE STUDY OF METFORMIN GSK 850 MG TABLETS MANUFACTURED BY SAVIPHARM J.S.C, VIETNAM AND GLUCOPHAGE® 850 MG TABLETS MANUFACTURED BY MERCK SANTE S.A.S.2, RUE DU PRESSOIR VERT-45400 SEMOY-FRANCE AND BE REGISTERED IN VIETNAM IN HEALTHY, ADULT, HUMAN MALE SUBJECTS UNDER FASTING CONDITION
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 主要终点
- Cmax, Tmax, AUC0-t, AUC0-∞, AUC%_Extrap, Kel and t1/2
研究概览
简要总结
A randomized, balanced, open label, crossover, two period, two treatment, two sequence, single dose, oral bioequivalence study under fasting condition. It is a pivotal study to demonstrate the bioequivalence of Metformin 850 mg tablets manufactured by Savipharm J.S.C, Vietnam and Glucophage® 850 mg tablets of Merck Sante, France, in healthy adult human male subjects under fasting condition.
详细描述
Sample Size Estimation Assuming the formulation ratio (T/R) 95-105% and with the maximum observable intra subject variability for Metformin is 22% (based on literature), a sample size of 29 subjects would be sufficient to prove bioequivalence between the two formulations with power of at least 90%. Hence, total 32 subjects will be enrolled in the study considering withdrawal and dropouts.
Screening procedures: Demographic data, medical and medication histories, complete physical examination, height, weight and BMI as well as 12 lead ECG, chest X-ray [PA view], vital signs [blood pressure, pulse rate, respiratory rate and oral temperature], hematology, biochemistry, HIV 1 & 2, Hepatitis B and C, RPR test for Syphilis and urine analysis will be done at screening.
Urine drug screen, Liver chemistry test and breath alcohol test to be done prior to each check-in.
Breath alcohol test to be done prior to each ambulatory visit blood collection. Liver chemistry test to be done at the end of each period. Housing: The study subjects will be housed at least 11 h prior to drug administration until after the 24 h blood sampling in each study period. The housing will be followed by one ambulatory visits [36.0 hr post dose] for each period.
Washout: At least 7 days, but not exceeding 14 days between two dosing days. Treatment arms: Test: A single dose of Metformin 500 mg tablet manufactured by Savipharm J.S.C, Vietnam.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy adult male human subjects within the age range of 18 to 45 years inclusive.
- •Weight not less than 50 kg.
- •Normal BMI [18.5 to 24.99 kg/m2 inclusive].
- •Willingness and capability to provide written informed consent to participate in the study.
- •Free of significant diseases or clinically significant abnormal findings based on medical history, physical examination, laboratory evaluations, 12-lead ECG, Chest X-ray [PA view].
- •Absence of disease markers of HIV 1 and 2, Hepatitis B and C and Syphilis.
- •AST, ALT, alkaline phosphatase and bilirubin </=1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- •ECG normal for morphology and measurements. QTcB or QTcF < 450 msec or QTc < 480 msec in subjects with Bundle Branch Block, based on an average from three ECGs obtained over a brief recording period.
- •Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed below. This criterion must be followed from the time of the first dose of study medication until one week of last dose administration.
- •Condom plus partner use of a highly effective contraceptive such as occlusive cap (diaphragm or cervical/vault cap) plus spermicidal agent (foam/gel/film/cream/suppository), oral contraceptive, injectable progesterone, implant of etonogestrel or levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, or intrauterine device.
- •Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
排除标准
- •History or presence of significant: Cardiovascular, pulmonary, hepatic, renal, hematological, gastro-intestinal, endocrine, immunologic, dermatologic, neurological, psychiatric disease.
- •History or presence of significant:
- •Alcohol dependence, alcohol abuse during past one year.
- •Drug abuse [Marijuana [THC], Cocaine, Morphine, Benzodiazepines, Barbiturates and Amphetamine] for the last 6 months.
- •Smoking of more than 5 cigarettes per day or consumption of other forms of tobacco containing products.
- •Asthma, urticaria or other allergic type reactions after taking aspirin or any other drug.
- •Ulceration or history of gastric and / or duodenal ulcer.
- •Jaundice in the past 6 months.
- •Bleeding disorder.
- •Allergy to the test drug or any drug chemically similar to the drug or to the excipients of the products under investigation.
- •Donation of 500 mL or more blood within 8 weeks prior to receiving the first dose of study drug.
- •Subjects who have participated in another clinical study in the past 3 months prior to commencement of this study.
- •Any difficulty in accessibility of forearm veins for cannulation or blood sampling.
- •Refusal to abstain from food for at least 10 h prior to drug administration and for at least 4 h post dose in each period.
- •Refusal to abstain from fluid for at least 1 h prior to and 1 h post each dose except 20 % glucose solution given after dosing.
- •Positive breath alcohol test result found on the day of check-in.
- •Positive urine test result for drug of abuse found on the day of check-in.
- •History of difficulty in swallowing tablet.
- •Use of any concomitant medication [including over-the-counter products, vitamins etc.] for 14 days preceding the study drug administration.
- •Use of drugs which induce or inhibit metabolizing enzymes within 30 days prior to receiving the first dose of study medication.
- •Other Eligibility Criteria Considerations To assess any potential impact on subject eligibility with regard to safety, the investigator must refer to the product data sheet for detailed information regarding warnings, precautions, contraindications, adverse events, and other significant data pertaining to the product being used in this study.
研究组 & 干预措施
Metformin GSK 850mg
open label, crossover, two period, two treatment, two sequence, single dose of Metformin 850mg
干预措施: Metformin GSK 850mg (Other)
Metformin GSK 850mg
open label, crossover, two period, two treatment, two sequence, single dose of Metformin 850mg
干预措施: Gluocophage 850mg (Other)
Glucophage 850mg
open label, crossover, two period, two treatment, two sequence, single dose
干预措施: Metformin GSK 850mg (Other)
Glucophage 850mg
open label, crossover, two period, two treatment, two sequence, single dose
干预措施: Gluocophage 850mg (Other)
结局指标
主要结局
Cmax, Tmax, AUC0-t, AUC0-∞, AUC%_Extrap, Kel and t1/2
时间窗: 7days
Statistical analyses will be done using SAS® version 9.2 or higher. Analysis of variance \[ANOVA\] for log-transformed pharmacokinetic parameters \[Cmax, AUC0-t and AUC0-∞\] and two one-sided tests \[Schuirmann\] for bioequivalence will be performed. Power, ratio and 90% confidence interval for log-transformed pharmacokinetic parameters - Cmax, AUC0-t and AUC0-∞ will be calculated. The calculated 90% Confidence Interval for the test to reference ratio of Metformin should fall within the range of 80%-125% for log transformed Cmax, AUC0-t and AUC0-∞ for the conclusion of bioequivalence.
次要结局
- Safety profile(14 days)