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

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.