A Partial Randomized, Single-blind or Open-label, Dose-escalation With Multiple-dose Design Study to Evaluate the Pharmacokinetics of Acetaminophen and Its Toxic Metabolites With Panadol® and SafeTynadol® in Healthy Volunteers
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- ALT level within study periods
研究概览
简要总结
To investigate and compare the possible response of Panadol® and SafeTynadol® formulations in healthy volunteers and the safety in SafeTynadol® dose-limiting hepatotoxicity.
详细描述
Subjects will be randomized to Cohort 1 and cohort 2 in the study without crossover, Cohort 3-8 will be a dose-escalation manner. An effort will be made to balance the number of males and females in each cohort.
The first treatment cohort 1 and 2 will enroll 12 study volunteers. The volunteers of cohort 1 will receive Panadol® oral dosage form is 500 mg*2 tablets = 1,000 mg/ person every 6 hours daily of the multiple-dose treatment (Q6H, total 4 dosages, 8 tablets, 4,000 mg) (n = 6) and cohort 2 will receive SafeTynadol® oral dosage form is 500 mg*2 tablets = 1,000 mg/ person every 6 hours daily of the multiple-dose treatment (Q6H, total 4 dosages, 8 tablets, 4,000 mg) (n = 6) in an single-blind, randomized manner.
About one to three weeks later, cohorts 3-8 will be studied in an order of increasing dose of SafeTynadol® starting from 4,500 mg increment to a maximum dose of 12,000 mg of SafeTynadol® if the previous cohort do not meet the significant criteria of hepatotoxicity.
Cohort 3-8 will initially enroll 3 study volunteers. Volunteers will receive SafeTynadol® oral dosage form is 500 mg*3 tablets at first dosage (1500 mg) and 500 mg every 6 hours *2 tablets at second to fourth dosage (1000 mg) person every 6 hours daily of the multiple-dose treatment (Q6H, total 4 dosages, 9 tablets, 4,500 mg) at cohort 3 or Volunteers will receive SafeTynadol® oral dosage form is 500 mg*3 tablets at first and second dosage (1500 mg) and 500 mg every 6 hours *2 tablets at third and fourth dosage (1000 mg) person every 6 hours daily of the multiple-dose treatment (Q6H, total 4 dosages, 10 tablets, 5,000 mg) at cohort 4 or Volunteers will receive SafeTynadol® oral dosage form is 500 mg*3 tablets = 1,500 mg/ person every 6 hours daily of the multiple-dose treatment (Q6H, total 4 dosages, 12 tablets, 6,000 mg) at cohort 5 or Volunteers will receive SafeTynadol® oral dosage form is 500 mg*4 tablets = 2,000 mg/ person every 6 hours daily of the multiple-dose treatment (Q6H, total 4 dosages, 16 tablets, 8,000 mg) at cohort 6 or Volunteers will receive multiple doses of SafeTynadol® oral dosage form 500 mg every 6 hours * 5 tablets = 2,500 mg/person every 6 hours daily of the multiple-dose treatment (Q6H, 4 doses, 20 tablets, 10,000 mg) at Cohort 7 or Volunteers will receive multiple doses of SafeTynadol® oral dosage form 500 mg every 6 hours * 6 tablets = 3,000 mg/person every 6 hours daily of the multiple-dose treatment (Q6H, 4 doses, 24 tablets, 12,000 mg) at Cohort 8.
In Cohort 3-8, liver function tests will be administered two hours after the third dose to confirm that the hepatotoxicity criteria are not met before the fourth dose can be administered and Cohort 6-8 will perform liver function tests two hours after the second dose administered to confirm that the hepatotoxicity criteria are not met before the third dose can be administered. After 3 study volunteers to confirm that did not meet significant hepatotoxicity occurs then another 3 study volunteers were included, study will in a dose-escalation manner.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 20 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Normal healthy adult subjects between 20-50 years of age.
- •Body weight within 80-120% of ideal body weight.
- •Male Ideal body weight = (height - 80) x 0.7
- •Female Ideal body weight = (height - 70) x 0.6
- •Acceptable medical history and physical examination including:
- •normal ECG results within six months prior to dosing.
- •no particular clinical significance in general disease history within two months prior to dosing.
- •Acceptable clinical laboratory determinations without significant deviation from normal values within two months prior to dosing, which includes AST (SGOT), ALT (SGPT), r-GT, alkaline phosphatase, total bilirubin, albumin, glucose, BUN, uric acid, creatinine, total cholesterol, triglyceride (TG), PT(INR) and OGSP.
- •Acceptable hematology within two months prior to dosing, which includes hemoglobin, hematocrit, red blood cells, MCV, MCH, MCHC, white blood cells, differential white blood cells and platelets.
- •Acceptable urinalysis within two months prior to dosing, which includes pH, blood, glucose and protein.
- •Signed the written informed consent to participate in this study
排除标准
- •History or presence of alcohol abuse, defined as consumption of more than 210 mL of alcohol per week (the equivalent of 14 glasses of 120-mL wine or 14 cans of 350-mL beer), or other substance abuse within the prior two years.
- •A clinically significant disorder involving the allergy, cardiovascular, respiratory, renal, gastrointestinal/hepatic, immunologic, hematologic, endocrine or neurologic system(s) or psychiatric disease (as determined by the clinical investigator).
- •History of allergic response(s) to acetaminophen, mannitol, sucralose or related drugs.
- •History of clinically significant allergies including drug allergies or allergic bronchial asthma.
- •Evidence of chronic or acute infectious diseases.
- •Any clinically significant illness or surgery during the two month prior to dosing (as determined by the clinical investigator).
- •Taking any drug known to induce or inhibit hepatic drug metabolism within one month prior to the beginning of the study.
- •Receiving any investigational drug within one month prior to dosing.
- •Taking any prescription medication or any nonprescription medication within two weeks prior to dosing.
- •Donating greater than 150 ml of blood within two months prior to dosing or donating plasma (e.g. plasmapheresis) within two weeks prior to dosing.
- •Consumption of caffeine, xanthine-containing products (i.e. coffee, tea, caffeine-containing sodas, colas and chocolate, etc.) and/or alcohol within 48 hours prior to days on which dosing is scheduled and during the periods when blood samples are being collected.
- •Any other medical reason as determined by the clinical investigator.
- •Subject is pregnant or breastfeeding.
- •Women of childbearing potential disagree to use an acceptable method of contraception (e.g., hormonal contraceptives, intrauterine device (IUD), barrier device or abstinence) throughout the study.
研究组 & 干预措施
Panadol
• Cohort 1- 6 Subjects to receive oral Panadol® 4,000 mg (2 tablets Q6H, 4 dosages, 8 tablets or 4,000 mg)
干预措施: Panadol® (Drug)
SafeTynadol®
- Cohort 2- 6 Subjects to receive oral SafeTynadol® 4,000 mg (2 tablets Q6H, 4 dosages, 8 tablets or 4,000 mg)
- Cohort 3- 6 Subjects to receive oral SafeTynadol® 4,500 mg (3 tablets at first dosage and 2 tablets at second to forth dosage Q6H, 4 dosages, 9 tablets or 4,500 mg)
- Cohort 4- 6 Subjects to receive oral SafeTynadol® 5,000 mg (3 tablets at first to second dosage and 2 tablets at third to forth dosage Q6H, 4 dosages, 10 tablets or 5,000 mg)
- Cohort 5- 6 Subjects to receive oral SafeTynadol® 6,000 mg (3 tablets Q6H, 4 dosages, 12 tablets or 6,000 mg)
- Cohort 6- 6 Subjects to receive oral SafeTynadol® 8,000 mg (4 tablets Q6H, 4 dosages, 16 tablets or 8,000 mg)
- Cohort 7- 6 Subjects to receive oral SafeTynadol® 10,000 mg (5 tablets Q6H, 4 dosages, 20 tablets or 10,000 mg)
- Cohort 8- 6 Subjects to receive oral SafeTynadol® 12,000 mg (6 tablets Q6H, 4 dosages, 24 tablets or 12,000 mg)
干预措施: SafeTynadol® (Drug)
结局指标
主要结局
ALT level within study periods
时间窗: Day 1-9
次要结局
- Incidence of peak ALT elevations > 8X ULN within study periods(Day 1-9)
- Incidence of total bilirubin > 2.5mg/dL within study periods(Day 1-9)
- Incidence of peak ALT elevations > 1X ULN within study periods(Day 1-9)
- Incidence of peak ALT elevations > 3X ULN within study periods(Day 1-9)
- Incidence of peak ALT elevations > 2X ULN within study periods(Day 1-9)
- Incidence of peak ALT elevations > 5X ULN within study periods(Day 1-9)
- Incidence of PT (INR) > 1.25 within study periods(Day 1-9)
- Hepatic failure rate(Day 1-9)
- Free plasma acetaminophen-cysteine (AAP-Cys) and AAP-Cys adducts(Day 1-9)
- The time-interval weighted area under the curve (AUC) of ALT level within study periods(Day 1-9)