Bioequivalence study,
Conditions
Interventions
coated tablet,
Arava® 20 mg,
Reg. No. 1C 78/42(N).,Generic leflunomide 20 mg film-
coated tablet.
Active Comparator Drug,Active Comparator Drug
coated tablet (Reference product),Leflunomide 20 mg film-
Sponsors
International Bio Service Co., Ltd.
Eligibility
Sex/Gender
Male
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1 Healthy Thai male subjects between the ages of 18 to 55 years. 2 Body mass index between 18 to 25 kg/m2. 3 Normal laboratory values, including vital signs and physical examination, for all parameters in clinical laboratory tests at screening. Any abnormalities from the normal or reference range will be carefully considered clinically relevant by the physician as individual cases, documented in study files prior to enrolling the subject in this study. 4 Non-smoker and/or non-consumer of nicotine containing products 5 Male subjects who are not wishing to father a child during the study or who are willing or able to use effective contraceptive e.g. condom or abstinence after admission until at least 30 days after investigational product administration. 6 Have voluntarily given written informed consent (signed and dated) by the subject prior to participating in this study.
Exclusion criteria
Exclusion criteria: 1 History of allergic reaction or hypersensitivity to leflunomide (especially previous Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme), teriflunomide or any of the excipients in the tablet 2 History of allergic reaction or hypersensitivity to cholestyramine 3 History or evidence of clinically significant renal, hepatic e.g. jaundice, gastrointestinal e.g. colitis, hematological e.g. anemia, endocrine e.g. thyroid, diabetes, pulmonary e.g. interstitial pneumonitis, pulmonary fibrosis, tuberculosis or respiratory e.g. asthma, cardiovascular, psychiatric, neurologic e.g. epilepsy, joint and bone e.g. rheumatoid arthritis or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) or any significant ongoing chronic medical illness 4 History or evidence of easy bruising or bleeding, recurrent infections, fever, paleness or unusual tiredness 5 History or evidence of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption 6 History of problems with swallowing tablet 7 History of sensitivity to heparin or heparin-induced thrombocytopenia 8 Any condition possibly affecting drug absorption e.g. oral mucous membrane lesions, gastrectomy, enterectomy, gastritis or duodenal or gastric ulceration other than appendectomy 9 History of dehydration from diarrhea, vomiting, excess sweating or any other reason within 24 hours prior to admission or prior to dosing 10 History or evidence of drug addict or investigation with urine sample shows a positive test for drug of abuse (morphine, marijuana or methamphetamine) 11 12-lead ECG demonstrating QTc >450 msec, a QRS interval >120 msec or with an abnormality considered clinically significant at screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG will be repeated two more times and the average of the three QTc or QRS values will be used to determine the subject’s eligibility. 12 Investigation with blood sample shows positive test for HBsAg 13 Abnormal liver function,  1.5 times of upper normal limit of reference range for ALT, AST or bilirubin levels at screening laboratory test 14 Have sitting systolic blood pressure of less than 90 mmHg or more than 139 mmHg and diastolic blood pressure of less than 60 mmHg or more than 89 mmHg on screening day and the day of admission. If abnormal blood pressure detects, the measurement will be repeated two more times after take a rest for at least 5 minutes each. The last measurement value will be used to determine the subject’s eligibility. 15 Investigation with blood sample shows albumin level less than 3.5 g/dl or more than 5.2 g/dl at screening 16 Investigation with blood sample shows total protein level less than 6.4 g/dl or more than 8.3 g/dl at screening 17 History or evidence of alcoholism, regular alcohol consumption or alcohol-containing products and cannot abstain for at least 7 days prior to admission and continued until last sample collection 18 History or evidence of habitual consume of tea, coffee, xanthine or caffeine containing products and cannot abstain for at least 7 days prior to admission and continued until last sample collection 19 Consumption or drinking of grapefruit juice or orange or its supplement/containing produ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Teriflunomide plasma concentration 0,0.33,0.67,1,1.5,2,2.5,3,3.5,4,5,6,7,8,12,16,24,48,72 h post-dose Cmax and Truncated AUC0-72 | — |
Secondary
| Measure | Time frame |
|---|---|
| Teriflunomide plasma concentration 0,0.33,0.67,1,1.5,2,2.5,3,3.5,4,5,6,7,8,12,16,24,48,72 h post-dose Tmax, t1/2 and lampda z | — |
Countries
Thailand
Contacts
Public ContactPorranee Puranajoti
International Bio Service Co. Ltd.
Outcome results
None listed