Bioavailability and Pharmacodynamic study (phase1) of Disgren EC capsule(Triflusal 300mg)

Status : Approved
First Submitted Date : 2014/11/20     Registered Date : 2014/12/05     Last Updated Date : 2014/12/05    

A randomized, open-label, multiple-dose, two-period, two-treatment, comparative crossover study involving 38 healthy adult males. 
The clinical trial was to determine the bioequivalence and non-inferiority of two different triflusal formulations. During each period, each subject received a single 900 mg oral loading dose on Day 1, followed by a 600 mg/day maintenance dose (given as two 300 mg capsules once daily) from Day 2 to 9.

Triflusal capsule (Disgren capsule, 300 mg), as the reference formulation, and triflusal EC capsule (Disgren enteric-coated capsule, 300 mg), as the test formulation were manufactured and provided by Myung-In Pharm. Co., Ltd (Seoul, Republic of Korea). The subjects received the test or reference formulation in multiple doses, followed by a 13-day washout period and subsequent administration of the alternative formulation. During each period, each subject received a single 900 mg oral loading dose on Day 1, followed by a 600 mg/day maintenance dose (given as two 300 mg capsules once daily) from Day 2 to 9.

Group 1

For period 1, each subject received Disgren capsule as single 900 mg oral loading dose on Day 1, followed by a 600 mg/day maintenance dose (given as two 300 mg capsules once daily) from Day 2 to 9. For period 2, each subject received Disgren enteric-coated capsule as single 900 mg oral loading dose on Day 1, followed by a 600 mg/day maintenance dose (given as two 300 mg capsules once daily) from Day 2 to 9.

Group 2

For period 1, each subject received Disgren enteric-coated capsule as single 900 mg oral loading dose on Day 1, followed by a 600 mg/day maintenance dose (given as two 300 mg capsules once daily) from Day 2 to 9. For period 2, each subject received Disgren capsule as single 900 mg oral loading dose on Day 1, followed by a 600 mg/day maintenance dose (given as two 300 mg capsules once daily) from Day 2 to 9.

•Healthy male subjects between the ages of 20 and 55 years at screening; 
•No abnormal symptom or sign, based on medical history and physical examination, with no congenital or chronic disease that requires treatment;
•Subject that is considered eligible for participating in the study by an investigator, based on clinical laboratory test (hematology, clinical chemistry, urinalysis, etc.);
•Hemorrhagic tendencies from medical history.

•Use of barbital drugs or alcohol abuse within 1 month prior to the study initiation; 
•Use of drugs disrupting this study  within 10 days prior to the study initiation; 
•Medical history of clinically significant hypersensitivity to study drug; 
•Subject that is not eligible to participate at this study, based on discretion of study investigator; 
•Smoker; 
•Clinical abnormalities at clinical laboratory test.
  - The levels of aspartate aminotransferase (serum glutamic oxaloacetic transaminase) or alanine aminotransferase (serum glutamic pyruvic transaminase) > 1.25 x the upper limit of normal
  - The levels of Total bilirubin > 1.25 x the upper limit of normal
  - Platelet count(<180,000 or >350,000)
  - prothrombin time (PT), activated partial thromboplastin time (aPTT) , and bleeding time (BT) > normal

AUC(area under the concentration-time curve)

pre-dose(0), post-dose 24, 48, 96, 144, 168, 192, 192.5, 193, 194, 196, 199, 202, 216 h 

Emax

pre-dose(0), post-dose 24, 48, 96, 144, 168, 192, 196, 202, 216 h 

Tmax(the time of Cmax)

pre-dose(0), post-dose 24, 48, 96, 144, 168, 192, 192.5, 193, 194, 196, 199, 202, 216 h